Nuclear MedicineFree Access

Review of ¹⁸F-Fluciclovine PET for Detection of Recurrent Prostate Cancer

Published Online:May 6 2019https://doi.org/10.1148/rg.2019180139

Abstract

Fluorine 18 (¹⁸F) fluciclovine (anti-1-amino-3–¹⁸F-fluorocyclobutane-1-carboxylic acid [FACBC]) is a radiolabeled amino acid analog that takes advantage of the amino acid transport upregulation in several types of cancer cells. FACBC is taken up to a greater extent in prostate cancer cells than in surrounding normal tissue, providing an opportunity for its use in cases of this common cancer. In 2016, the U.S. Food and Drug Administration found the accuracy of FACBC PET to be superior to that of other molecular imaging techniques and subsequently granted approval for its use in PET of recurrent prostate cancer. As FACBC is an ¹⁸F radiotracer, an on-site cyclotron is not required for its production. This feature enables the widespread clinical availability of this agent and, in turn, an opportunity for improved patient care. The clinical pharmacology and imaging features of FACBC are reviewed, and the role of this agent in the imaging of recurrent prostate cancer, within the context of research that supports its effectiveness, is discussed. The administration of and image acquisition facilitated by using FACBC, as compared with ¹⁸F fluorodeoxyglucose, which is more widely used, are described. In addition, the criteria for interpreting FACBC imaging findings are outlined, with emphasis on common causes of false-positive and false-negative findings.

^©RSNA, 2019

SA-CME LEARNING OBJECTIVES

After completing this journal-based SA-CME activity, participants will be able to:

■ Describe the imaging and clinical pharmacology features of FACBC.
■ Discuss the relevant details of FACBC administration and the associated image acquisition in contrast to those associated with FDG, the more widely used agent.
■ List the criteria used to interpret FACBC imaging findings in the setting of suspected recurrent prostate cancer.

Introduction

Prostate cancer is the second leading cause of cancer-related mortality in men (1). At least one-third of patients who undergo definitive treatment have cancer relapse (2,3). Recurrent disease is typically discovered owing to an increase in prostate-specific antigen (PSA) levels. However, the location and extent of recurrence cannot be easily or accurately assessed by means of conventional imaging, and this limitation complicates treatment management (4). There is no agreement regarding the size of the pelvic radiation field in patients with recurrent disease, and the presence of extrapelvic metastatic disease typically excludes patients from salvage radiation therapy (5,6). Therefore, identification of the extent of pelvic disease and detection of extrapelvic metastases significantly affect plans for subsequent salvage radiation therapy (7).

Fluorine 18 (¹⁸F) fluciclovine, or anti-1-amino-3–¹⁸F-fluorocyclobutane-1-carboxylic acid (FACBC), was developed to address the shortcomings of current imaging techniques. This compound takes advantage of the increased amino acid transport in prostate cancer cells. Labeling with ¹⁸F enables the widespread clinical use of FACBC. The use of FACBC was approved by the U.S. Food and Drug Administration (FDA) in May of 2016, and this agent is now available for imaging of suspected prostate cancer recurrence following treatment (3).

Physiologic Distribution of FACBC

FACBC is a radiolabeled analog of levorotatory leucine, which is an essential amino acid. Like levorotatory leucine, FACBC is taken up via the human L-type amino acid transporter and alanine-serine-cysteine transporter systems. As such, FACBC demonstrates the highest uptake in tissues that produce proteins or process amino acids. L-type amino acid transporter and alanine-serine-cysteine transporter systems are upregulated in many carcinomas, including prostate cancer, with the L-type amino acid and alanine-serine-cysteine transporter subtypes associated with more aggressive disease (8–10).

Once inside the cell, FACBC does not undergo metabolism and can transit out of the cell via the same channels through which it entered. A comparison of the different ways that different prostate imaging radiopharmaceuticals interact with prostate cancer cells is shown in Figure 1.

Figure 1. Drawing illustrates how five commonly used prostate imaging radiopharmaceuticals interact with a prostate cancer cell. ¹⁸F fluorodeoxyglucose *(FDG),* FACBC, and carbon 11 (¹¹C) choline enter through the glucose transporter 1–glucose transporter 3 *(GLUT1/3)*, L-type amino acid transporter–alanine-serine-cysteine transporter 2 *(LAT/ASCT2),* and choline transporters, respectively. Among these channel-transiting compounds, FACBC is the only one that is free to enter and exit the cell; FDG is trapped in the cell owing to the Krebs cycle, and ¹¹C-choline becomes incorporated into the cell membrane. Gadolinium 68 (⁶⁸*Ga)* prostate-specific membrane antigen *(PSMA)* 11 is a larger molecule that interacts with the extracellular active zone of PSMA. Indium 111 (¹¹¹*In)* capromab pendetide (Prostascint; EUSA Pharma, Langhorne, Pa), another large compound, is an antibody-bound complex in which the antibody targets an intracellular PSMA glycoprotein. This complex can enter only necrotic prostate cancer cells, as it relies on the loss of phospholipid membrane integrity.

FACBC Imaging Characteristics

As in other publications that describe FACBC, in this review, we characterize the intensity of FACBC uptake that indicates potential malignancy by comparing this uptake with that in the blood pool, bone marrow, and liver. Avidity equal to or greater than that of the blood pool but less than that of the bone marrow is considered to be mild. Avidity equal to or greater than that of bone marrow but less than that of the liver is considered to be moderate. Avidity equal to or greater than that of the liver is considered to be intense.

The most intense physiologic tracer uptake is seen in the pancreas (Fig 2). However, this uptake decreases within 15 minutes after injection of the radiopharmaceutical such that the avidity of the pancreas decreases to a level lower than that of the liver. The liver has the second most intense physiologic activity and is the critical organ (11,12). There is moderate salivary gland and pituitary gland uptake and variable mild to moderate bowel activity (11). Two tissue types demonstrate dynamic uptake, which changes during the course of the scanning examination: Red marrow activity peaks at a moderate intensity 10–15 minutes after the injection and decreases over time. Conversely, muscle uptake is mild during the early phases of the examination and increases over time.

Figure 2. Coronal caudal-to-cranial PET scan acquired 4 minutes after the injection of FACBC shows the normal distribution of the radiotracer. Intense physiologic uptake is present in the pancreas *(P),* with moderate to intense uptake in the liver *(L),* the critical organ. Little renal excretion (ovals) is seen, and the activity in the bladder *(B)* is mild. Activity in the muscles increases during scanning, with the muscle activity in the upper thigh and pelvis (dashed arrows) less prominent than that in the upper arms and neck (solid arrows).

There is minimal to no activity in the excreted urine, and even when FACBC accumulates in the bladder, the accumulation is much milder than that of FDG, and it rarely interferes with image interpretation.

Occasionally, a patient has early bladder wall activity, which may need to be considered when the deep pelvis is evaluated. Other organs without significant uptake include the lungs and the brain, although the pituitary gland demonstrates mild to moderate activity in the majority of individuals.

Due to the rapid influx and efflux of amino acids and thus FACBC in prostate cancer, the pathologic activity in prostate tumors and nodal metastatic disease peaks rapidly, between 4 and 10 minutes, after the radiotracer injection (Fig 3).

This is in stark contrast to the pathologic activity of FDG, which peaks within 45–90 minutes in most tumors. In fact, by 90 minutes, greater than 60% of the FACBC at peak tumoral activity has washed out (12). The dynamic findings in tumor cells and muscle tissue dictate the imaging protocol. PET imaging begins 3–5 minutes after the injection of radiotracer.

Scanning from the midthigh to the skull base (caudal to cranial) optimizes the target-to–background tissue ratio by maximizing pathologic pelvic uptake while minimizing uptake in the background muscle tissue.

Figure 3. Time-activity curves show mean standardized uptake values *(SUVs)* in various tissues at 90 minutes after the administration of FACBC. (Reprinted, with permission, from Blue Earth Diagnostics.)

Accuracy

Before May of 2016, only two radiotracers were FDA approved for imaging in the setting of biochemical recurrence of prostate cancer: ¹¹¹In–capromab pendetide was approved in 1999, and ¹¹C-choline was approved in 2012. Given this factor, the FDA focused its review on two studies (13,14) during the process of approving the use of FACBC. In these studies, FACBC PET/CT was compared with ¹¹¹In–capromab pendetide SPECT/CT at Emory University (13) and with ¹¹C-choline PET/CT at the University of Bologna (14).

In the Emory University study (13), 93 patients suspected of having recurrent prostate cancer underwent FACBC PET/CT and ¹¹¹In–capromab pendetide SPECT/CT within 90 days of each other. The images were interpreted by two blinded readers, with consensus reading performed in discordant cases. A consensus panel determined whether patients were believed to have prostate or prostatectomy bed disease. Patients with extraprostatic findings at FACBC PET/CT or ¹¹¹In–capromab pendetide SPECT/CT underwent targeted biopsy. The effectiveness of FACBC imaging findings was compared with that of the histologic results. FACBC imaging had higher sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in the detection of prostate, prostatectomy bed, and extraprostatic disease compared with ¹¹¹In–capromab pendetide imaging (Table 1).

**Table 1: Performance of FACBC and ¹¹¹In–Capromab Pendetide Scanning in 93 Patients**

Source.—Reference 13.

Note.—Data are performance values for FACBC and ¹¹¹In–capromab pendetide scanning in the detection of prostate, prostatectomy bed, or extraprostatic disease in 93 patients at Emory University who were suspected of having recurrent prostate cancer. NPV = negative predictive value, PPV = positive predictive value.

Compared with ¹¹¹In–capromab pendetide scanning, FACBC scanning depicted 14 more prostatectomy bed tumor recurrences (55 vs 41) and enabled the identification of 18 more patients with extraprostatic involvement (22 versus four). FACBC scanning results led to correct tumor grade upgrading in 18 (26%) of 70 cases. In addition, the amount of patient radiation exposure in the FACBC examinations was approximately one-third the amount in the ¹¹¹In–capromab pendetide examinations.

In the University of Bologna study (14), 50 patients suspected of having recurrent prostate cancer underwent FACBC PET/CT and ¹¹C-choline PET/CT within 1 week of each other. The images were interpreted by two blinded readers, with consensus reading performed in discordant cases. Cancer recurrence was successfully identified with FACBC PET/CT in six patients whose ¹¹C-choline PET results were negative. There were no patients with negative FACBC PET/CT results but positive ¹¹C-choline scanning results. Results of the majority of the imaging examinations (n = 33) performed in the remaining patients were concurrently negative for recurrent prostate cancer.

Findings in the Emory University (Table 2) (13) and University of Bologna (14) studies demonstrated that the sensitivity of FACBC scanning increased with increasing PSA levels (15).

**Table 2: Performance Values for FACBC Scanning Based on PSA Levels**

Source.—Reference 13.

Note.—Data are negative predictive value (NPV) and positive predictive value (NPV) percentages for FACBC scanning of recurrent prostate cancer, based on PSA levels, from an FDA review of data from an Emory University study.

Similarly, in the setting of recurrent prostate cancer, the diagnostic performance of FACBC PET/CT has also been shown to be superior to that of conventional CT. In one study (16), 53 men with biochemical prostate cancer recurrence and negative bone scan findings underwent FACBC PET/CT and diagnostic CT within 90 days of each other. FACBC PET/CT had a fourfold higher true-positive result rate and double the accuracy compared with CT. FACBC scanning also enabled much better delineation of recurrent prostate versus extraprostatic cancer at all PSA levels, PSA doubling times, and original Gleason scores (16).

The significance of these study findings is best illustrated by the results of the phase III FALCON (Fluciclovine [¹⁸F] PET/CT in biochemicAL reCurrence Of prostate caNcer) trial (17), in which the important effects of FACBC PET/CT on the treatment of patients with biochemical recurrence of prostate cancer were studied. In this study involving 85 patients, FACBC scan findings led to revision of the treatment plan for 52 men. Sixty percent of these cases involved major changes in the planned treatment, with salvage therapy changed to systemic therapy or watchful waiting. The other 40% of cases involved modification of the planned radiation therapy.

Since the FDA approval of FACBC use in 2016, progress has been made with another PET imaging agent, ⁶⁸Ga–PSMA 11, in the imaging of prostate cancer. In a recent international study (18) involving 270 patients suspected of having prostate cancer recurrence following radical prostatectomy, PSMA 11 facilitated the identification of 132 patients with positive imaging findings. This population included only those patients whose PSA levels were lower than 1 ng/mL. This is notable because FACBC PET is less likely to yield positive results in patients with PSA levels lower than 1 ng/mL, unless the doubling time is rapid.

However, there are limited data on the direct comparison of FACBC with PSMA 11. Calais et al (19) performed a retrospective head-to-head comparison of these two agents. Their study involved 10 patients who were enrolled in a PSMA 11 trial and had previously undergone FACBC PET/CT within 0.2–4.2 months (mean, 2.3 months) of subsequent PSMA 11 imaging. The PSMA 11 examination appeared to be more sensitive in this group, with positive PSMA 11 scan findings and discordantly negative FACBC scan findings in five (50%) of the 10 patients. In an additional two (20%) of the 10 patients, both examinations had positive findings; however, the PSMA 11 scans showed additional sites of disease.

The Calais et al study (19) was limited in that only one patient had histologic confirmation, the median 2.6-month interval between the FACBC and PSMA 11 examinations favored lesion detection with PSMA 11 scanning, and there was bias in the selection of patients who underwent FACBC PET/CT and subsequent PSMA 11 imaging.

Imaging Protocol

Patient Preparation

To help decrease their muscle uptake, patients are instructed to avoid strenuous exercise the day before they are scheduled to undergo FACBC scanning. Patients are also asked to fast for at least 4 hours before the imaging examination to decrease their levels of circulating amino acids that may compete with FACBC for uptake (20). In addition, they are instructed to not void for 30 minutes before the FACBC injection. This instruction is based on the expert opinion that a full bladder may decrease the amount of FACBC that is excreted into the bladder and/or cause the dilution of any excreted radiotracer (21).

Radiotracer Injection and Image Acquisition

The radiotracer is injected with the patient placed supine on the PET/CT scanning bed. Following the injection, the arms are repositioned above the head and CT scanning is initiated. This usually facilitates the initiation of PET scan acquisition 3–5 minutes (target, 4 minutes) following the injection. We instruct our technologists to pause if less than 3 minutes have passed, as increased blood pool activity may be encountered if scanning is started too early.

Scanning is initiated at the upper thigh and proceeds cranially to the base of the skull, with a total imaging time of approximately 20–30 minutes. This allows for an approximately 5-minute image acquisition time in the pelvic bed position, with 3–5 minutes per bed position cranial to the pelvis. However, these times should be optimized for specific equipment (21). Figure 4 summarizes a typical FACBC scanning protocol.

Figure 4. Drawing illustrates the timeline for patient preparations before FACBC scanning, and the imaging protocol. Patient instructions and imaging procedures are shown on the left of the timeline, and the rationales for these are illustrated on the right.

This protocol is in stark contrast to that for FDG PET, in which blood glucose levels are monitored immediately before the injection, scans are obtained after an uptake period of 45–90 minutes, and patients are instructed to void immediately before the scanning examination (Table 3).

**Table 3: Important Differences between FACBC PET and FDG PET Imaging Protocols**

Image Interpretation Criteria

General Approach

FACBC uptake is assessed visually rather than by relying on SUVs. Pathologic lesion uptake, as compared with the uptake in surrounding normal structures, should be focal and stand out visually. Soft-tissue sites of avidity for which the anatomic correlate is 1 cm or larger are considered abnormal if the avidity is greater than or equal to that of bone marrow. Currently, the uptake in the L3 vertebral body is used as a standardized reference value for bone marrow avidity. For focal uptake for which the anatomic correlate is smaller than 1 cm, uptake in the blood pool is used as the internal reference (Table 4).

**Table 4: Image Interpretation Criteria Based on Anatomic Location**

Note.—MIP = maximum intensity projection, NaF = sodium fluoride.

*Mixed refers to bone lesions that have both lytic and sclerotic components.

The FACBC uptake pattern and associated findings at CT or other correlative imaging modalities are usually the most helpful for identifying malignant lesions. However, SUV measurements may be helpful at sites that are questionable in terms of the presence of prostate cancer recurrence according to comparisons between the SUV of the site and the reference SUV of the nontarget background tissue (eg, L3 vertebra for bone marrow). If the maximal SUV for the lesion in question exceeds the mean SUV for the L3 vertebral body by at least 20%, there is cause for concern for recurrent disease (22).

Prostate and Prostatectomy Bed

In patients who have undergone prostatectomy, focal lesions with avidity greater than or equal to that of bone marrow are suspicious for cancer (Fig 5). However, if a focus of avidity is small (<1 cm), then it must be compared with the avidity of the blood pool (Fig 6). Subcentimeter foci of avidity are considered suspicious only if their avidity significantly exceeds that of the blood pool. It should be noted that in the manufacturer’s prescribing information (12), review of only coronal PET images is recommended for aiding in the interpretation of prostate and prostatectomy bed findings.

Figure 5a. Cancer recurrence in a 65-year-old man with a newly detected biochemical recurrence after prior prostatectomy. **(a)** Axial fused PET/CT image shows intense FACBC uptake (arrowhead) in the anterior prostatectomy bed, just behind the right pubic tubercle, that is significantly more intense than the physiologic bone marrow uptake and consistent with cancer recurrence. The soft-tissue correlate seen at concurrently performed non–contrast material–enhanced CT (not shown) was an oval soft-tissue structure. **(b)** Previously obtained axial surveillance contrast-enhanced CT image shows a 1.2-cm enhancing ovoid soft-tissue nodule (arrow) that had not been detected.

Figure 5b. Cancer recurrence in a 65-year-old man with a newly detected biochemical recurrence after prior prostatectomy. **(a)** Axial fused PET/CT image shows intense FACBC uptake (arrowhead) in the anterior prostatectomy bed, just behind the right pubic tubercle, that is significantly more intense than the physiologic bone marrow uptake and consistent with cancer recurrence. The soft-tissue correlate seen at concurrently performed non–contrast material–enhanced CT (not shown) was an oval soft-tissue structure. **(b)** Previously obtained axial surveillance contrast-enhanced CT image shows a 1.2-cm enhancing ovoid soft-tissue nodule (arrow) that had not been detected.

Figure 6a. Biochemical cancer recurrence in a 71-year-old man after prior prostatectomy. Axial PET **(a)** and fused PET/CT **(b)** images show a subcentimeter focus of moderately intense FACBC uptake (arrowhead) in the central pelvis. The uptake is significantly more intense than the physiologic uptake in the blood pool (oval in a) and thus raises concern for locally recurrent disease.

Figure 6b. Biochemical cancer recurrence in a 71-year-old man after prior prostatectomy. Axial PET **(a)** and fused PET/CT **(b)** images show a subcentimeter focus of moderately intense FACBC uptake (arrowhead) in the central pelvis. The uptake is significantly more intense than the physiologic uptake in the blood pool (oval in a) and thus raises concern for locally recurrent disease.

In patients who have not undergone prostatectomy, focal asymmetric (Fig 7) or multifocal heterogeneous (Fig 8) avidity that is greater than or equal to that of bone marrow is suspicious for tumor recurrence. Diffuse homogeneous prostate gland avidity should be suspected for recurrent cancer if it is much greater than the avidity of bone marrow. However, a homogeneous uptake pattern in the prostate gland is atypical for recurrence, and other entities that can result in FACBC uptake, such as benign prostatic hypertrophy, prostatitis, and postradiation inflammation, also should be considered (Fig 9). As such, higher false-positive rates are seen in patients with an intact prostate.

Figure 7a. Findings in a 62-year-old man with a history of prostate cancer treated with radiation therapy. Recurrent disease was identified owing to serially increasing PSA levels following the posttreatment nadir. **(a)** Axial fused PET/CT image shows intense uptake (arrowhead) in the deep pelvis corresponding to the left lobe of the prostate. **(b)** Corresponding axial nonenhanced CT image does not show an anatomic correlate (arrow).

Figure 7b. Findings in a 62-year-old man with a history of prostate cancer treated with radiation therapy. Recurrent disease was identified owing to serially increasing PSA levels following the posttreatment nadir. **(a)** Axial fused PET/CT image shows intense uptake (arrowhead) in the deep pelvis corresponding to the left lobe of the prostate. **(b)** Corresponding axial nonenhanced CT image does not show an anatomic correlate (arrow).

Figure 8. Axial fused PET/CT image in a 59-year-old man with a history of rare ductal carcinoma of the prostate and increasing PSA levels shows two foci of FACBC uptake (arrows) in the prostate. The uptake intensity is greater than that of bone marrow and thus suspicious for active disease.

Figure 9a. Biochemical recurrence in a 66-year-old man after prior radiation therapy. **(a)** Axial CT image acquired at FACBC PET/CT shows an enlarged prostate (circle) without focal abnormality. **(b)** Axial fused FACBC PET/CT image shows homogeneously intense uptake (arrowhead) that is much greater than that in the bone marrow throughout the prostate. Images obtained during the remainder of the examination (not shown) showed no concerning lymph nodes or bone lesions. Although this uptake pattern is suspicious for recurrence, it could also be related to benign prostatic hypertrophy, prostatitis, or radiation therapy.

Figure 9b. Biochemical recurrence in a 66-year-old man after prior radiation therapy. **(a)** Axial CT image acquired at FACBC PET/CT shows an enlarged prostate (circle) without focal abnormality. **(b)** Axial fused FACBC PET/CT image shows homogeneously intense uptake (arrowhead) that is much greater than that in the bone marrow throughout the prostate. Images obtained during the remainder of the examination (not shown) showed no concerning lymph nodes or bone lesions. Although this uptake pattern is suspicious for recurrence, it could also be related to benign prostatic hypertrophy, prostatitis, or radiation therapy.

Subcentimeter foci of uptake are considered to be suspicious for recurrence only if they are significantly more avid than the blood pool. It should be noted that there have been anecdotal reports of focal median lobe uptake with a high likelihood of being false positive for recurrence; thus, this uptake finding should be viewed with a degree of skepticism.

Lymph Nodes

When evaluating lymph nodes, one must consider whether their uptake features are typical or atypical of prostate cancer recurrence. The typical sites of nodal recurrence are the pelvic and retroperitoneal regions, including para-aortic, common iliac, internal iliac, and proximal external iliac nodal regions. When assessing focal uptake that corresponds to an enlarged lymph node in a typical site of prostate cancer spread, avidity greater than or equal to that of bone marrow is considered to be suspicious (Fig 10). The absence of such uptake favors a lymph node that is free of disease (Fig 11). As in the evaluation for possible prostate or prostatectomy bed recurrence, when evaluating lymph nodes for possible recurrence, subcentimeter nodes should be considered suspicious when their FACBC uptake significantly exceeds that of the blood pool (Fig 12).

Figure 10a. Suspected recurrent prostate cancer in a 59-year-old man with an enlarged right internal iliac lymph node at prior diagnostic CT. **(a)** Coronal MIP image shows moderately intense FACBC uptake (solid arrow) in the right pelvis, as well as FACBC with unusually intense activity (dashed arrow) excreted in the bladder. The masslike uptake (arrowhead) in the central abdomen is a benign pancreatic head lesion, which is prominent owing to severe atrophy of the pancreatic body and tail. **(b, c)** The moderately FACBC-avid enlarged right internal iliac lymph node (arrow) is better seen on the CT **(b)** and fused PET/CT **(c)** images and was deemed to be suspicious for recurrence.

Figure 10b. Suspected recurrent prostate cancer in a 59-year-old man with an enlarged right internal iliac lymph node at prior diagnostic CT. **(a)** Coronal MIP image shows moderately intense FACBC uptake (solid arrow) in the right pelvis, as well as FACBC with unusually intense activity (dashed arrow) excreted in the bladder. The masslike uptake (arrowhead) in the central abdomen is a benign pancreatic head lesion, which is prominent owing to severe atrophy of the pancreatic body and tail. **(b, c)** The moderately FACBC-avid enlarged right internal iliac lymph node (arrow) is better seen on the CT **(b)** and fused PET/CT **(c)** images and was deemed to be suspicious for recurrence.

Figure 10c. Suspected recurrent prostate cancer in a 59-year-old man with an enlarged right internal iliac lymph node at prior diagnostic CT. **(a)** Coronal MIP image shows moderately intense FACBC uptake (solid arrow) in the right pelvis, as well as FACBC with unusually intense activity (dashed arrow) excreted in the bladder. The masslike uptake (arrowhead) in the central abdomen is a benign pancreatic head lesion, which is prominent owing to severe atrophy of the pancreatic body and tail. **(b, c)** The moderately FACBC-avid enlarged right internal iliac lymph node (arrow) is better seen on the CT **(b)** and fused PET/CT **(c)** images and was deemed to be suspicious for recurrence.

Figure 11a. Findings in a 60-year-old man who had recurrent prostate cancer, with focal FACBC uptake in the left prostate lobe (not shown). **(a)** Axial CT image shows a 1.3-cm right common iliac lymph node (arrow). **(b)** Axial fused PET/CT image shows that the node (arrow) has minimal avidity, with the intensity of uptake in the node approaching that of the adjacent blood pool. **(c)** Axial PET image findings confirm that the radiotracer uptake (oval) is not significantly greater than that of the background tissue. This node was not deemed to be suspicious for prostate cancer.

Figure 11b. Findings in a 60-year-old man who had recurrent prostate cancer, with focal FACBC uptake in the left prostate lobe (not shown). **(a)** Axial CT image shows a 1.3-cm right common iliac lymph node (arrow). **(b)** Axial fused PET/CT image shows that the node (arrow) has minimal avidity, with the intensity of uptake in the node approaching that of the adjacent blood pool. **(c)** Axial PET image findings confirm that the radiotracer uptake (oval) is not significantly greater than that of the background tissue. This node was not deemed to be suspicious for prostate cancer.

Figure 11c. Findings in a 60-year-old man who had recurrent prostate cancer, with focal FACBC uptake in the left prostate lobe (not shown). **(a)** Axial CT image shows a 1.3-cm right common iliac lymph node (arrow). **(b)** Axial fused PET/CT image shows that the node (arrow) has minimal avidity, with the intensity of uptake in the node approaching that of the adjacent blood pool. **(c)** Axial PET image findings confirm that the radiotracer uptake (oval) is not significantly greater than that of the background tissue. This node was not deemed to be suspicious for prostate cancer.

Figure 12. Recurrent prostate cancer, diagnosed on the basis of increasing PSA levels, in a 69-year-old man. Axial fused PET/CT image shows a subcentimeter lymph node (arrowhead) in the left proximal external iliac chain. The node has avidity markedly greater than that of the blood pool and is thus suspicious for active disease. Renally excreted FACBC with unusual activity (dashed arrow) is present in the ureter. The circumferential avidity (solid arrow) of the thickened bladder wall likely represents inflammatory mural uptake of FACBC due to cystitis; however, physiologic bladder wall uptake in a small number of patients has been described.

Atypical sites of nodal spread include the inguinal, distal external iliac, hilar, and axillary regions. Mild symmetric uptake in these nodes typically is physiologic (Fig 13). However, if uptake is present in the setting of other, clearly malignant disease (Fig 14) or it cannot be explained by the clinical history and/or an adjacent pathologic process (eg, vascular graft placement, arthroplasty), then it may be considered suspicious for prostate cancer recurrence. The caveat to this is that FACBC can be taken up by nonprostate cancer cells, as other carcinomas also upregulate amino acid transport. Breast and colon cancers are frequently implicated mimics of prostate cancer, and lymphoma is an occasional mimic. Therefore, if a cluster of FACBC-avid lymph nodes with a distribution resembling that of another cancer is encountered, then the images should be scrutinized for evidence of a second primary cancer.

Figure 13a. Recurrent prostate cancer, diagnosed on the basis of increasing PSA levels, in a 61-year-old man with a history of prior prostatectomy. **(a)** Axial nonenhanced CT image shows bilateral subcentimeter inguinal lymph nodes (arrowheads) that are morphologically normal. **(b)** Axial PET/CT image reveals associated mild symmetric FACBC avidity. The inguinal region is an atypical site of prostate cancer spread, and the lymph nodes (arrowheads) demonstrate only mild symmetric uptake, which is physiologic.

Figure 13b. Recurrent prostate cancer, diagnosed on the basis of increasing PSA levels, in a 61-year-old man with a history of prior prostatectomy. **(a)** Axial nonenhanced CT image shows bilateral subcentimeter inguinal lymph nodes (arrowheads) that are morphologically normal. **(b)** Axial PET/CT image reveals associated mild symmetric FACBC avidity. The inguinal region is an atypical site of prostate cancer spread, and the lymph nodes (arrowheads) demonstrate only mild symmetric uptake, which is physiologic.

Figure 14a. Recurrent prostate cancer, diagnosed on the basis of increasing PSA levels, in a 65-year-old man with a history of prior prostatectomy. **(a, b)** Axial FACBC PET **(a)** and fused PET/CT **(b)** images show moderately intense uptake (arrowhead) along the distal right external iliac vessels. **(c)** Axial CT image shows a corresponding subcentimeter lymph node (arrow) with uptake that is much greater than that in the blood pool. There are no adjacent surgical changes (ie, hernia repair mesh, vascular graft, hip prosthesis) to cause reactive changes. Therefore, this node is moderately suspicious for recurrence.

Figure 14b. Recurrent prostate cancer, diagnosed on the basis of increasing PSA levels, in a 65-year-old man with a history of prior prostatectomy. **(a, b)** Axial FACBC PET **(a)** and fused PET/CT **(b)** images show moderately intense uptake (arrowhead) along the distal right external iliac vessels. **(c)** Axial CT image shows a corresponding subcentimeter lymph node (arrow) with uptake that is much greater than that in the blood pool. There are no adjacent surgical changes (ie, hernia repair mesh, vascular graft, hip prosthesis) to cause reactive changes. Therefore, this node is moderately suspicious for recurrence.

Figure 14c. Recurrent prostate cancer, diagnosed on the basis of increasing PSA levels, in a 65-year-old man with a history of prior prostatectomy. **(a, b)** Axial FACBC PET **(a)** and fused PET/CT **(b)** images show moderately intense uptake (arrowhead) along the distal right external iliac vessels. **(c)** Axial CT image shows a corresponding subcentimeter lymph node (arrow) with uptake that is much greater than that in the blood pool. There are no adjacent surgical changes (ie, hernia repair mesh, vascular graft, hip prosthesis) to cause reactive changes. Therefore, this node is moderately suspicious for recurrence.

Musculoskeletal System

Focal osseous uptake that is clearly visualized on MIP or PET images can be considered suspicious for cancer (Fig 15). Lytic bone metastases typically show intense FACBC avidity. Mixed (lytic and sclerotic) bone lesions most commonly show moderate uptake. Even in the absence of FACBC uptake, if a densely sclerotic osseous abnormality with morphology that raises concern is visualized at CT, then metastasis must be considered. However,

densely sclerotic metastatic lesions may have no FACBC uptake.

Further evaluation can be performed with alternative imaging modalities such as MRI, ¹⁸F–sodium fluoride PET/CT, and technetium 99m–medronate SPECT/CT.

Figure 15a. Recurrent prostate cancer diagnosed on the basis of increasing PSA levels in a 73-year-old man with a history of prior prostatectomy. **(a)** Coronal MIP image shows numerous foci of intense radiotracer uptake in the axial and proximal appendicular skeleton. Note the relative osseous photopenia in the pelvis, which is typical of prior radiation therapy–induced changes. **(b, c)** Axial PET **(b)** and CT **(c)** images show avidity (arrowhead), representing a sclerotic lesion, with no anatomic pathologic uptake correlate (arrows) in the vertebra, rib, or scapula.

Figure 15b. Recurrent prostate cancer diagnosed on the basis of increasing PSA levels in a 73-year-old man with a history of prior prostatectomy. **(a)** Coronal MIP image shows numerous foci of intense radiotracer uptake in the axial and proximal appendicular skeleton. Note the relative osseous photopenia in the pelvis, which is typical of prior radiation therapy–induced changes. **(b, c)** Axial PET **(b)** and CT **(c)** images show avidity (arrowhead), representing a sclerotic lesion, with no anatomic pathologic uptake correlate (arrows) in the vertebra, rib, or scapula.

Figure 15c. Recurrent prostate cancer diagnosed on the basis of increasing PSA levels in a 73-year-old man with a history of prior prostatectomy. **(a)** Coronal MIP image shows numerous foci of intense radiotracer uptake in the axial and proximal appendicular skeleton. Note the relative osseous photopenia in the pelvis, which is typical of prior radiation therapy–induced changes. **(b, c)** Axial PET **(b)** and CT **(c)** images show avidity (arrowhead), representing a sclerotic lesion, with no anatomic pathologic uptake correlate (arrows) in the vertebra, rib, or scapula.

Although degenerative disk and facet uptake of FACBC is sometimes seen, it is less common and less intense than FDG uptake. Therefore, focal intense uptake for which the anatomic correlate suggests degenerative disease should be carefully assessed and considered within the context of degenerative versus malignant skeletal uptake elsewhere (Fig 16). Mild FACBC uptake in the appendicular skeleton is less worrisome, especially if there is a convincing CT correlate consistent with osteoarthritis, but it is less common and less intense compared with the uptake of FDG usually seen in this condition. Occasionally, a nonprostate malignancy such as multiple myeloma or a metastatic lesion from a second primary cancer is detected.

Figure 16a. Primary prostate cancer (Gleason score, 8; PSA level, 11 ng/mL) in a 69-year-old man. **(a)** Coronal MIP image shows a focus of moderately intense radiotracer uptake (oval) in the left shoulder region. **(b)** Axial fused PET/CT image reveals that the uptake corresponds to the scapula (green arrowhead), with an adjacent focus of moderate inflammatory uptake (yellow arrowhead) involving the rotator cuff. **(c)** Axial CT image shows a morphologically benign, circumscribed, mixed (lytic and sclerotic) lesion (arrow) in the subchondral aspect of the glenoid fossa. Given the CT findings and the solitary nature of this uptake in a patient with no additional extraprostatic findings (not shown), the lesion was believed to represent a geode or other benign entity. This was confirmed at review of prior imaging findings, which indicated long-term stability in the absence of prior therapy.

Figure 16b. Primary prostate cancer (Gleason score, 8; PSA level, 11 ng/mL) in a 69-year-old man. **(a)** Coronal MIP image shows a focus of moderately intense radiotracer uptake (oval) in the left shoulder region. **(b)** Axial fused PET/CT image reveals that the uptake corresponds to the scapula (green arrowhead), with an adjacent focus of moderate inflammatory uptake (yellow arrowhead) involving the rotator cuff. **(c)** Axial CT image shows a morphologically benign, circumscribed, mixed (lytic and sclerotic) lesion (arrow) in the subchondral aspect of the glenoid fossa. Given the CT findings and the solitary nature of this uptake in a patient with no additional extraprostatic findings (not shown), the lesion was believed to represent a geode or other benign entity. This was confirmed at review of prior imaging findings, which indicated long-term stability in the absence of prior therapy.

Figure 16c. Primary prostate cancer (Gleason score, 8; PSA level, 11 ng/mL) in a 69-year-old man. **(a)** Coronal MIP image shows a focus of moderately intense radiotracer uptake (oval) in the left shoulder region. **(b)** Axial fused PET/CT image reveals that the uptake corresponds to the scapula (green arrowhead), with an adjacent focus of moderate inflammatory uptake (yellow arrowhead) involving the rotator cuff. **(c)** Axial CT image shows a morphologically benign, circumscribed, mixed (lytic and sclerotic) lesion (arrow) in the subchondral aspect of the glenoid fossa. Given the CT findings and the solitary nature of this uptake in a patient with no additional extraprostatic findings (not shown), the lesion was believed to represent a geode or other benign entity. This was confirmed at review of prior imaging findings, which indicated long-term stability in the absence of prior therapy.

Intense but benign activity within a joint or at a muscular insertion also has been observed occasionally. Increased muscle uptake of FACBC is often seen following exercise (Fig 17).

Figure 17a. Biochemical recurrence of prostate cancer in a 59-year-old man. **(a)** Coronal MIP image obtained at FACBC PET/CT shows two fusiform sites of abnormal radiotracer uptake (arrows) in the medial thighs. **(b)** Axial fused PET/CT image shows that the increased avidity (arrowheads) corresponds to morphologically normal adductor longus muscles. Physiologic muscle uptake is typically more diffuse and is seen most frequently in the upper torso and extremities, as caudal-to-cranial PET image acquisition facilitates a greater accumulation of radiotracer in these areas. In this case, the isolated nature of the uptake, which involves only the adductor longus muscles and is greater than that of more cranial muscles, makes this FACBC avidity typical of exercise- or injury-induced inflammation.

Figure 17b. Biochemical recurrence of prostate cancer in a 59-year-old man. **(a)** Coronal MIP image obtained at FACBC PET/CT shows two fusiform sites of abnormal radiotracer uptake (arrows) in the medial thighs. **(b)** Axial fused PET/CT image shows that the increased avidity (arrowheads) corresponds to morphologically normal adductor longus muscles. Physiologic muscle uptake is typically more diffuse and is seen most frequently in the upper torso and extremities, as caudal-to-cranial PET image acquisition facilitates a greater accumulation of radiotracer in these areas. In this case, the isolated nature of the uptake, which involves only the adductor longus muscles and is greater than that of more cranial muscles, makes this FACBC avidity typical of exercise- or injury-induced inflammation.

Solid Viscera

In contrast to the renal excretion of FDG, there is minimal renal excretion of FACBC at the time of scanning. This may be due to the recommended protocol of imaging at 3–5 minutes after the injection in contrast to imaging at 60 minutes after the injection of FDG or other PSMA tracers. Therefore, the kidneys have no significant avidity on scans of normal findings. If renal masses are present, then any focal uptake associated with these lesions should be considered suspicious for malignancy. Schuster et al (23) studied the FACBC PET findings in a small number of patients who had clear cell (n = 4) or papillary (n = 2) renal cell carcinoma that was subsequently determined at histologic analysis. They noted the FACBC uptake in the papillary lesions to be increased relative to that in the renal parenchyma and the uptake in the clear cell lesions to be equal to or less than that in the renal parenchyma (23).

In another study, Schuster et al (11) noted that 10%–15% of patients had unilateral or bilateral adrenal uptake, even when there was no apparent anatomic correlate. Adrenal adenomas may demonstrate mildly to moderately increased FACBC avidity (Fig 18). CT images and comparison studies are helpful for characterizing these lesions as benign adrenal tumors rather than adrenal metastases, which typically demonstrate intense uptake (Fig 19).

Figure 18a. Imaging findings in a 62-year-old man with increased PSA levels detected after prostatectomy. **(a)** Axial PET image shows a focus of mild FACBC uptake (arrowhead) between the superior pole of the right kidney and the posterior margin of the liver. **(b)** Axial fused PET/CT image shows avidity (arrowhead) localized to the right adrenal gland, with no uptake seen in the left adrenal gland (oval). **(c)** Axial CT image reveals a small nodule (arrow) in the right adrenal gland. Review of prior imaging findings (not shown) revealed long-term lesion stability, consistent with a benign adenoma. The nonavid left adrenal gland (oval) has normal morphology.

Figure 18b. Imaging findings in a 62-year-old man with increased PSA levels detected after prostatectomy. **(a)** Axial PET image shows a focus of mild FACBC uptake (arrowhead) between the superior pole of the right kidney and the posterior margin of the liver. **(b)** Axial fused PET/CT image shows avidity (arrowhead) localized to the right adrenal gland, with no uptake seen in the left adrenal gland (oval). **(c)** Axial CT image reveals a small nodule (arrow) in the right adrenal gland. Review of prior imaging findings (not shown) revealed long-term lesion stability, consistent with a benign adenoma. The nonavid left adrenal gland (oval) has normal morphology.

Figure 18c. Imaging findings in a 62-year-old man with increased PSA levels detected after prostatectomy. **(a)** Axial PET image shows a focus of mild FACBC uptake (arrowhead) between the superior pole of the right kidney and the posterior margin of the liver. **(b)** Axial fused PET/CT image shows avidity (arrowhead) localized to the right adrenal gland, with no uptake seen in the left adrenal gland (oval). **(c)** Axial CT image reveals a small nodule (arrow) in the right adrenal gland. Review of prior imaging findings (not shown) revealed long-term lesion stability, consistent with a benign adenoma. The nonavid left adrenal gland (oval) has normal morphology.

Figure 19a. Recurrent prostate cancer in a 63-year-old man. **(a)** Coronal MIP image shows focal intensely avid uptake (arrow) in the left middle region of the abdomen, as well as multifocal increased patchy uptake throughout the axial skeleton. **(b, c)** Axial fused PET/CT **(b)** and CT **(c)** images show that the intense avidity seen in a corresponds to a soft-tissue–attenuation nodule (arrowhead) in the left adrenal gland. Given the intensity of the avidity and the setting of widespread metastatic disease, this nodule was believed to represent a metastatic adrenal lesion.

Figure 19b. Recurrent prostate cancer in a 63-year-old man. **(a)** Coronal MIP image shows focal intensely avid uptake (arrow) in the left middle region of the abdomen, as well as multifocal increased patchy uptake throughout the axial skeleton. **(b, c)** Axial fused PET/CT **(b)** and CT **(c)** images show that the intense avidity seen in a corresponds to a soft-tissue–attenuation nodule (arrowhead) in the left adrenal gland. Given the intensity of the avidity and the setting of widespread metastatic disease, this nodule was believed to represent a metastatic adrenal lesion.

Figure 19c. Recurrent prostate cancer in a 63-year-old man. **(a)** Coronal MIP image shows focal intensely avid uptake (arrow) in the left middle region of the abdomen, as well as multifocal increased patchy uptake throughout the axial skeleton. **(b, c)** Axial fused PET/CT **(b)** and CT **(c)** images show that the intense avidity seen in a corresponds to a soft-tissue–attenuation nodule (arrowhead) in the left adrenal gland. Given the intensity of the avidity and the setting of widespread metastatic disease, this nodule was believed to represent a metastatic adrenal lesion.

Intracranial Structures

Primary brain tumors and brain metastases have variable FACBC uptake that is usually greater than that in the brain parenchyma, which has less uptake than the blood pool. Gliomas and meningiomas with FACBC uptake have been described (Fig 20). The normal pituitary gland demonstrates moderate FACBC uptake in the majority of patients (Fig 21); however, uptake in pituitary adenomas also has been reported (Fig 22) (11). Some investigators have also reported mild uptake in the choroid plexus (24).

Figure 20a. Biochemical recurrence of prostate cancer in a 71-year-old man. **(a)** Axial fused PET/CT image shows intense FACBC avidity (arrow) anterior to the pons. **(b)** Corresponding axial CT image shows a discoid high-attenuation lesion (arrow), representing a previously undetected meningioma, in the cerebrospinal fluid space.

Figure 20b. Biochemical recurrence of prostate cancer in a 71-year-old man. **(a)** Axial fused PET/CT image shows intense FACBC avidity (arrow) anterior to the pons. **(b)** Corresponding axial CT image shows a discoid high-attenuation lesion (arrow), representing a previously undetected meningioma, in the cerebrospinal fluid space.

Figure 21a. Suspected biochemical recurrence of prostate cancer in a 56-year-old man with a PSA level of 0.5 ng/mL. **(a)** Oblique-sagittal MIP image shows a mild to moderate focus of radiotracer uptake (arrow) in the central skull base. **(b)** Axial fused PET/CT image shows avidity (arrow) localized to the normal pituitary gland. A normal pituitary gland was confirmed by means of retrospective review of a previously obtained brain MR image.

Figure 21b. Suspected biochemical recurrence of prostate cancer in a 56-year-old man with a PSA level of 0.5 ng/mL. **(a)** Oblique-sagittal MIP image shows a mild to moderate focus of radiotracer uptake (arrow) in the central skull base. **(b)** Axial fused PET/CT image shows avidity (arrow) localized to the normal pituitary gland. A normal pituitary gland was confirmed by means of retrospective review of a previously obtained brain MR image.

Figure 22a. Findings in an 81-year-old man who underwent FACBC PET/CT for therapy guidance. **(a)** Coronal MIP image shows extensive metastatic prostate cancer, as well as an intense focus of uptake (arrow) in the region of the skull base. **(b)** Sagittal fused PET/CT image shows avidity localized to the pituitary gland, which contains a previously demonstrated macroadenoma (arrow).

Figure 22b. Findings in an 81-year-old man who underwent FACBC PET/CT for therapy guidance. **(a)** Coronal MIP image shows extensive metastatic prostate cancer, as well as an intense focus of uptake (arrow) in the region of the skull base. **(b)** Sagittal fused PET/CT image shows avidity localized to the pituitary gland, which contains a previously demonstrated macroadenoma (arrow).

Infection and Inflammation

Infectious and inflammatory processes may result in increased FACBC uptake. The data on this subject are still fairly anecdotal. We have seen cases in which pneumonia caused moderately intense FACBC uptake (Fig 23). Amzat et al (25) characterized their experience with two inflammatory pulmonary lesions, which had FACBC SUVs that were lower than those of several neoplastic lesions (n = 9) but higher than the SUV of a single pulmonary carcinoid tumor.

Figure 23a. Findings in a 62-year-old man with a high PSA level detected after prior prostatectomy. **(a)** Axial fused PET/CT image shows abnormal wedge-shaped FACBC uptake (green arrowhead) in the anterior left lung base. An additional round focus of uptake (yellow arrowhead) is present in the right lung base. **(b)** Axial CT image shows that the avidity (arrow) on the left side corresponds to ground-glass lingular airspace disease. This patient had been seen in the emergency department the prior evening for a cough and was diagnosed with pneumonia. No abnormality in the right lung base is seen on the CT image; the uptake seen in a represents misregistration artifact from the liver dome and from respiratory motion during PET image acquisition.

Figure 23b. Findings in a 62-year-old man with a high PSA level detected after prior prostatectomy. **(a)** Axial fused PET/CT image shows abnormal wedge-shaped FACBC uptake (green arrowhead) in the anterior left lung base. An additional round focus of uptake (yellow arrowhead) is present in the right lung base. **(b)** Axial CT image shows that the avidity (arrow) on the left side corresponds to ground-glass lingular airspace disease. This patient had been seen in the emergency department the prior evening for a cough and was diagnosed with pneumonia. No abnormality in the right lung base is seen on the CT image; the uptake seen in a represents misregistration artifact from the liver dome and from respiratory motion during PET image acquisition.

Moderate to intense FACBC uptake in inflammatory skin lesions and in sites of infection such as those with ringworm has been reported. In addition, we frequently see mild to moderate uptake at sites of subcutaneous injections (Fig 24).

Figure 24a. Findings in a 55-year-old man with prostate cancer recurrence. **(a)** Sagittal MIP image shows an abnormal accumulation of radiotracer (arrow) along the anterior abdominal wall. **(b)** Axial PET image shows two similar foci (arrowheads) in the superficial aspect of the left and right lower quadrants. **(c)** Corresponding axial CT image reveals the foci in b to be subcutaneous fat (arrowheads) of increased density corresponding to sites of insulin injections, which were part of a diabetes treatment regimen.

Figure 24b. Findings in a 55-year-old man with prostate cancer recurrence. **(a)** Sagittal MIP image shows an abnormal accumulation of radiotracer (arrow) along the anterior abdominal wall. **(b)** Axial PET image shows two similar foci (arrowheads) in the superficial aspect of the left and right lower quadrants. **(c)** Corresponding axial CT image reveals the foci in b to be subcutaneous fat (arrowheads) of increased density corresponding to sites of insulin injections, which were part of a diabetes treatment regimen.

Figure 24c. Findings in a 55-year-old man with prostate cancer recurrence. **(a)** Sagittal MIP image shows an abnormal accumulation of radiotracer (arrow) along the anterior abdominal wall. **(b)** Axial PET image shows two similar foci (arrowheads) in the superficial aspect of the left and right lower quadrants. **(c)** Corresponding axial CT image reveals the foci in b to be subcutaneous fat (arrowheads) of increased density corresponding to sites of insulin injections, which were part of a diabetes treatment regimen.

Schuster et al (11) reviewed the FACBC scans obtained in 598 subjects and noted mild to moderate linear esophageal uptake (Fig 25) in more than 50% of these subjects. The uptake tended to be most prominent in the distal esophagus and mimicked that seen with inflammatory reflux at FDG PET. Although FACBC uptake was not formally correlated with reflux esophagitis, the cause of this uptake was presumed to be based on the established relationship at FDG PET.

Figure 25. Sagittal MIP image obtained in a 59-year-old man shows a long segment of linear FACBC accumulation (arrowheads) in the posterior mediastinum, similar to a common finding seen at FDG PET/CT. This linear accumulation represents benign physiologic avidity rather than inflammatory avidity.

Anatomic Variants

Anatomic variants are most relevant in the head and neck. The salivary glands demonstrate moderate FACBC uptake, and accessory parotid glands are seen in up to 15% of the general population (Fig 26), with an additional 30%–35% of the general population demonstrating a prominent anterior facial process of the parotid gland (at CT) (26). These processes typically are seen lateral to the masseter muscle and anterior to the bulk of the parotid gland. Thyroid tissue demonstrates only mild activity (11). The lymphoid tissue in the Waldeyer throat ring also demonstrates moderate uptake, which may be prominent in some patients (11). Although it has not been specifically reported, we believe that it is possible for lingual thyroid tissue to demonstrate similar uptake.

Figure 26a. Findings in a 59-year-old man with biochemical recurrence. **(a)** Oblique-sagittal MIP image shows an unexpected focus of FACBC uptake (arrow) in the face. **(b)** Axial fused PET/CT image shows the uptake (green arrowhead) localized to the right cheek. Moderate physiologic uptake (yellow arrowhead) is present in the parotid gland, just posterior to the uptake in the cheek. **(c)** Axial coned-down CT image shows that the avidity in the cheek (arrow) correlates with soft tissue that has attenuation similar to that of the parotid gland and represents a benign accessory gland.

Figure 26b. Findings in a 59-year-old man with biochemical recurrence. **(a)** Oblique-sagittal MIP image shows an unexpected focus of FACBC uptake (arrow) in the face. **(b)** Axial fused PET/CT image shows the uptake (green arrowhead) localized to the right cheek. Moderate physiologic uptake (yellow arrowhead) is present in the parotid gland, just posterior to the uptake in the cheek. **(c)** Axial coned-down CT image shows that the avidity in the cheek (arrow) correlates with soft tissue that has attenuation similar to that of the parotid gland and represents a benign accessory gland.

Figure 26c. Findings in a 59-year-old man with biochemical recurrence. **(a)** Oblique-sagittal MIP image shows an unexpected focus of FACBC uptake (arrow) in the face. **(b)** Axial fused PET/CT image shows the uptake (green arrowhead) localized to the right cheek. Moderate physiologic uptake (yellow arrowhead) is present in the parotid gland, just posterior to the uptake in the cheek. **(c)** Axial coned-down CT image shows that the avidity in the cheek (arrow) correlates with soft tissue that has attenuation similar to that of the parotid gland and represents a benign accessory gland.

Future Directions

Primary Prostate Cancer Staging

Given the imaging characteristics of FACBC, there is reason to explore its use in the primary staging of prostate cancer. It seems that prostate MRI outperforms FACBC PET/CT in the characterization of prostate lesions (27). However, CT and MRI are not sufficiently sensitive in the detection of nodal disease (28). FACBC stands out in the characterization of invasive prostate disease and detection of early or distant nodal disease at the time of the diagnosis (Figs 27, 28). These features drive treatment change by enabling clinicians to define targets for surgical and radiation therapy (29). We expect future studies to help clinicians better characterize the magnitude of associated survival benefits of such treatment plan changes.

Figure 27. Newly diagnosed prostate cancer (Gleason score, 3 + 4) in a 55-year-old man with extensive disease. Coronal MIP image obtained at FACBC PET/CT before treatment shows the primary lesion (red arrow) in the right prostate lobe. Ipsilateral nodal spread is seen in the proximal external iliac chain (black arrow), common iliac region (red arrowhead), and distal para-aortic station (black arrowhead).

Figure 28. Prostate cancer (Gleason score, 4 + 4; PSA level, 30 ng/mL) in a 66-year-old man. Coronal MIP image shows bilateral multifocal disease (circle) in the prostate glands and a solitary bone metastasis lesion (arrow) in the left ilium, with no FACBC-avid nodal disease.

Imaging of Other Cancers

Many ¹⁸F-labeled amino acid analogs are being studied for possible use in PET of a variety of neoplasms (23,30,31). The most promising work has been in the field of breast cancer (30,32). In a study involving 27 women with locally advanced invasive ductal or invasive lobular carcinomas (33), FACBC PET/CT depicted local disease, biopsy-proven axillary nodal metastases, and even two previously unsuspected internal mammary nodes.

Conclusion

FACBC is the only ¹⁸F-based radiotracer that the FDA has approved for molecular imaging in patients suspected of having recurrent prostate cancer. The sensitivity of this radiotracer for the detection of recurrent and metastatic disease is higher than that of other nuclear medicine and CT agents. Physician and technologist familiarity with the FACBC imaging protocol is essential to the successful integration of this examination into existing FDG PET/CT techniques. In addition, having well-rounded knowledge of the common patterns of prostate cancer recurrence and a proper awareness of the associated image interpretation criteria is critical to maximizing the use of this new molecular imaging tool.

Acknowledgment

The authors are grateful to Erica L. Vasquez of the Brooke Army Medical Center Electronic Multimedia Image Center for creating the illustrations in Figures 1 and 4.

Recipient of a Certificate of Merit award at the 2017 RSNA Annual Meeting.

For this journal-based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant relationships.

The views expressed are those of the authors and do not reflect the official views or policies of the Department of Defense or its components.

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Article History

Received: Apr 6 2018
Revision requested: May 30 2018
Revision received: June 23 2018
Accepted: July 13 2018
Published online: May 06 2019
Published in print: May 2019

Vol. 39, No. 3

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Abbreviations

Abbreviations:
FACBC	anti-1-amino-3–¹⁸F-fluorocyclobutane-1-carboxylic acid
FDA	U.S. Food and Drug Administration
FDG	fluorine 18 fluorodeoxyglucose
MIP	maximum intensity projection
PSA	prostate-specific antigen
PSMA	prostate-specific membrane antigen
SUV	standardized uptake value

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Review of 18F-Fluciclovine PET for Detection of Recurrent Prostate Cancer