Pictorial essay: incidental findings on 18F-Fluciclovine PET/CT scan

Abstract Introduction Fluorine-18 (18F) Fluciclovine (anti-1-amino-3-18F-fluorocyclobutane- 1-carboxylic acid [FACBC]) is a synthetic amino acid labeled with 18F, currently used as PET radiopharmaceutical to investigating prostate cancer, namely in the recurrent setting. Fluciclovine is transported to cell membranes by amino acid transporters, such as LAT1 and ASCT2. The upregulation of LAT-1 and ASCT2 activities is typical of prostate cancer but is also present in other pathological conditions such as non-prostatic neoplasms (e.g., lung cancer) and in benign inflammatory process (e.g., benign prostatic hyperplasia, chronic prostatitis, high-grade prostatic hyperplasia intraepithelial). Methods In this short essay we present a retrospective FACBC PET/CT analysis consisting of a selection of the five most relevant cases of patients referred in our centre to FACBC PET/CT for prostate cancer, with concomitant FACBC uptake in sites atyipical for prostate cancer. Results These five selected cases demonstrate FACBC uptake at the level of the pancreatic head, adrenal incidentalomas, pulmonary nodules, mediastinal lymph nodes and neoformative tissue of the rectal wall. Discussion Clinical cases selected in this pictorial essay have demonstrated that Fluciclovine is not an exclusive and specific radiotracer for prostate cancer and, therefore, can induce misdiagnosis. In fact, incidental benign and malignant uptake might occur and should be further evaluated with clinical correlation or other imaging.

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Accumulation of Trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Prostate Cancer due to Androgen-Induced Expression of Amino Acid Transporters

Molecular Imaging and Biology ◽

10.1007/s11307-014-0756-x ◽

2014 ◽

Vol 16 (6) ◽

pp. 756-764 ◽

Cited By ~ 19

Author(s):

Hiroyuki Okudaira ◽

Shuntaro Oka ◽

Masahiro Ono ◽

Takeo Nakanishi ◽

David M. Schuster ◽

...

Keyword(s):

Prostate Cancer ◽

Amino Acid ◽

Amino Acid Transporters ◽

Induced Expression

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Current evaluation of the clinical utility of Fluoromethylcholine-(18F) PET/CT in Prostate Cancer

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132008000700012 ◽

2008 ◽

Vol 51 (spe) ◽

pp. 71-75

Author(s):

Jean-Nöel Talbot ◽

Yanna-Marina Chevalme

Keyword(s):

Prostate Cancer ◽

False Negative ◽

Distant Metastases ◽

Short Review ◽

Current Status ◽

Current Evidence ◽

Cancer Tissue ◽

Negative Results ◽

Pet Ct ◽

Pet Radiopharmaceutical

This short review is dedicated to the current status of the assessment of a new PET radiopharmaceutical, fluoromethylcholine-(18F) or FCH, which is taken-up by prostate cancer tissue, in contrary to fluorodeoxyglucose-(18F) or FDG. It seems that FCH could become "the FDG of prostate cancer", with the same type of achievements (detection of distant metastases and of occult recurrences, restaging prior to invasive treatments), and the same drawbacks (false negative results in case of small lesions, in particular lymph nodes metastases, and false positive results in case of infection/inflammation, in particular prostatitis). Current evidence is summarised and discussed for each of the potential settings of FCH PET/CT imaging in prostate cancer. The perspectives for granting a marketing authorisation to a FCH preparation are briefly analysed.

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Understanding and Improving 18F-Fluciclovine PET/CT Reports: A Guide for Physicians Treating Patients with Biochemical Recurrence of Prostate Cancer

Prostate Cancer ◽

10.1155/2020/1929565 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Benjamin H. Lowentritt ◽

Michael S. Kipper

Keyword(s):

Prostate Cancer ◽

Amino Acid ◽

Biochemical Recurrence ◽

Specific Antigen ◽

The Body ◽

Bone Lesions ◽

Detection Rates ◽

Pet Ct ◽

Management Plans ◽

Referring Physicians

The positron emission tomography (PET) tracer 18F-fluciclovine has seen increasing use to localize disease in men with biochemical recurrence of prostate cancer, i.e., elevated prostate-specific antigen (PSA) levels post-treatment. 18F-Fluciclovine PET/computed tomography (CT) imaging reports now play central roles in many physician-patient discussions. However, because no standardized grading system or templates yet exist for 18F-fluciclovine image assessment, reports vary in format, comprehensiveness, and terminology and may be challenging to fully understand. To better utilize these documents, referring physicians should be aware of six key features of 18F-fluciclovine PET/CT. First, 18F-fluciclovine is a radiolabeled synthetic amino acid targeting the amino acid transporters ASCT2 and LAT1, which are ubiquitous throughout the body, but overexpressed in prostate cancer. Second, 18F-fluciclovine image interpretation is predominantly visual/qualitative: radiotracer uptake in suspicious lesions is compared with uptake in bone marrow or blood pool. Location of 18F-fluciclovine-avid lesions relative to typical recurrence sites and findings elsewhere in the patient are considered when evaluating lesions’ probability of malignancy, as is visibility on maximum intensity projection images when assessing bone lesions. Third, 18F-fluciclovine PET/CT detection rates increase as PSA levels rise. Fourth, detection rates may differ among centers, possibly due to equipment and reader experience. Fifth, since no diagnostic test is 100% accurate, scan data should not be used in isolation. Lastly, 18F-fluciclovine PET/CT findings frequently induce changes in disease management plans. In the prospective multicenter LOCATE and FALCON studies, scans altered management plans in 59% (126/213) and 64% (66/104) of patients, respectively; 78% (98/126) and 65% (43/66) of changes, respectively, involved modality switches. Referring physicians and imagers should collaborate to improve scan reports. Referrers should clearly convey critical information, including prescan PSA levels, and open clinical questions. Imagers should produce reports that read like consultations, avoid leaving open questions, and if needed, provide thoughts on next diagnostic steps.

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Preclinical Evaluation of 11 C-Sarcosine as a Substrate of Proton-Coupled Amino Acid Transporters and First Human Application in Prostate Cancer

Journal of Nuclear Medicine ◽

10.2967/jnumed.116.173179 ◽

2017 ◽

Vol 58 (8) ◽

pp. 1216-1223 ◽

Cited By ~ 7

Author(s):

Morand Piert ◽

Xia Shao ◽

David Raffel ◽

Mathew S. Davenport ◽

Jeffrey Montgomery ◽

...

Keyword(s):

Prostate Cancer ◽

Amino Acid ◽

Amino Acid Transporters ◽

Preclinical Evaluation

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Combined Intravenous Urogram and 68Ga-PSMA PET/ CT for Improved Staging and Restaging of Prostate Cancer

Journal of Clinical Imaging Science ◽

10.25259/jcis_88_2020 ◽

2020 ◽

Vol 10 ◽

pp. 67

Author(s):

Rhiannon McBean ◽

Anisa Kumari ◽

Louise McEwan ◽

James Walters ◽

David Wong

Keyword(s):

Prostate Cancer ◽

Imaging Protocol ◽

Intravenous Urogram ◽

Positron Emission ◽

Psma Pet ◽

Pet Ct ◽

Imaging Approach ◽

Pictorial Essay ◽

Gallium 68 ◽

Specific Membrane

Staging/restaging of prostate cancer utilizing Gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in combination with an intravenous urogram allows improved discrimination between radiotracer activity in the renal tract and small pelvic nodes or local recurrences. Within this pictorial essay, we describe the imaging protocol utilized at our institution and present cases which demonstrate the utility of this combined imaging approach.

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18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy

EJNMMI Research ◽

10.1186/s13550-020-00728-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Gaurav Malviya ◽

Rachana Patel ◽

Mark Salji ◽

Rafael S. Martinez ◽

Peter Repiscak ◽

...

Keyword(s):

Prostate Cancer ◽

Amino Acid ◽

Cancer Cells ◽

Androgen Deprivation Therapy ◽

Metabolic Imaging ◽

Amino Acid Transporters ◽

Human Prostate Cancer ◽

Tumour Heterogeneity ◽

Castration Resistant

Abstract Background Prostate cancer is highly prevalent worldwide. Androgen deprivation therapy (ADT) remains the treatment of choice for incurable prostate cancer, but majority of patients develop disease recurrence following ADT. There is therefore an urgent need for early detection of treatment resistance. Methods Isogenic androgen-responsive (CWR22Res) and castration-resistant (22Rv1) human prostate cancer cells were implanted into the anterior lobes of the prostate in CD-1 Nu mice to generate prostate orthografts. Castrated mice bearing CWR22Res and 22Rv1 orthografts mimic clinical prostate cancer following acute and chronic ADT, respectively. 18F-Fluciclovine (1-amino-3-fluorocyclobutane-1-carboxylic acid) with a radiochemical purity of > 99% was produced on a FASTlab synthesiser. Ki67 staining in endpoint orthografts was studied. Western blot, quantitative RT-PCR and next-generation sequencing transcriptomic analyses were performed to assess the expression levels of amino acid transporters (including LAT1 and ASCT2, which have been implicated for Fluciclovine uptake). Longitudinal metabolic imaging with 18F-Fluciclovine-based positron emission tomography (PET) was performed to study tumour response following acute and chronic ADT. Results Both immunohistochemistry analysis of endpoint prostate tumours and longitudinal 18F-Fluciclovine imaging revealed tumour heterogeneity, particularly following ADT, with in vivo 18F-Fluciclovine uptake correlating to viable cancer cells in both androgen-proficient and castrated environment. Highlighting tumour subpopulation following ADT, both SUVpeak and coefficient of variation (CoV) values of 18F-Fluciclovine uptake are consistent with tumour heterogeneity revealed by immunohistochemistry. We studied the expression of amino acid transporters (AATs) for 18F-Fluciclovine, namely LAT1 (SLC7A5 and SLC3A2) and ASCT2 (SLC1A5). SLC7A5 and SLC3A2 were expressed at relatively high levels in 22Rv1 castration-resistant orthografts following chronic ADT (modelling clinical castration-resistant disease), while SLC1A5 was preferentially expression in CWR22Res tumours following acute ADT. Additional AATs such as SLC43A2 (LAT4) were shown to be upregulated following chronic ADT by transcriptomic analysis; their role in Fluciclovine uptake warrants investigation. Conclusion We studied in vivo 18F-Fluciclovine uptake in human prostate cancer orthograft models following acute and chronic ADT. 18F-Fluciclovine uptakes highlight tumour heterogeneity that may explain castration resistance and can be exploited as a clinical biomarker.

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Impact of PSMA PET/CT in prostate cancer patient’s clinical management: a pictorial essay of interesting cases with histologic confirmation

Clinical and Translational Imaging ◽

10.1007/s40336-020-00372-2 ◽

2020 ◽

Vol 8 (3) ◽

pp. 207-226

Author(s):

Sofia Carrilho Vaz ◽

Ângelo Silva ◽

Carla Oliveira ◽

Rita Marques ◽

António Galzerano ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Management ◽

Psma Pet ◽

Pet Ct ◽

Pictorial Essay

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Intra-patient comparison of physiologic 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia in prostate cancer patients: a pictorial essay

Cancer Imaging ◽

10.1186/s40644-021-00404-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Medhat M. Osman ◽

Amir Iravani ◽

Michael S. Hofman ◽

Rodney J. Hicks

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Metabolic Activity ◽

Pet Imaging ◽

Case Presentation ◽

Ct Examination ◽

Imaging Characteristics ◽

Pet Ct ◽

Pictorial Essay ◽

Anatomic Locations

Abstract Background Recent studies reported metabolic uptake in at least one of the evaluated ganglia in 98.5% of patients undergoing 68Ga -PSMA-11 and in 96.9% of patients undergoing 18F-DCFPyL PET/CT examination. We have observed different patterns of ganglion visualization with 18F-DCFPyL compared to 68Ga-PSMA-11. This includes more frequent visualization of cervical and sacral ganglia, which may be attributable to better imaging characteristics with 18F PET imaging. Case presentation This pictorial essay is to illustrate and compare, in the same patient, various representative cases of 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia at different anatomic locations, with different patterns and distribution of metabolic activity. Conclusion Reading physicians should be aware of the frequently encountered and occasionally different physiologic uptake of 68Ga-PSMA-11 and 18F DCFPyL in different ganglia.

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