fluciclovine-f-18 and Prostatic-Neoplasms--Castration-Resistant

Prostate cancer is a very heterogeneous disease, and contemporary management is focused on identification and treatment of the prognostically adverse high-risk tumors while minimizing overtreatment of indolent, low-risk tumors. In recent years, imaging has gained increasing importance in the detection, staging, posttreatment assessment, and detection of recurrence of prostate cancer. Several imaging modalities including conventional and functional methods are used in different clinical scenarios with their very own advantages and limitations. This continuing medical education article provides an overview of available imaging modalities currently in use for prostate cancer followed by a more specific section on the value of these different imaging modalities in distinct clinical scenarios, ranging from initial diagnosis to advanced, metastatic castration-resistant prostate cancer. In addition to established imaging indications, we will highlight some potential future applications of contemporary imaging modalities in prostate cancer.

Topics: Aged; Antigens, Surface; Carboxylic Acids; Choline; Cyclobutanes; Disease Progression; Fluorodeoxyglucose F18; Glutamate Carboxypeptidase II; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Multiparametric Magnetic Resonance Imaging; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Radionuclide Imaging; Theranostic Nanomedicine; Tomography, X-Ray Computed; Whole Body Imaging

18F-Fluciclovine is an amino acid-based radiopharmaceutical used primarily for PET imaging of patients with biochemical recurrence of prostate cancer. We report a case of a 66-year-old man with recently diagnosed metastatic castrate-resistant prostate cancer and a left supraclavicular lymph node with incidental radiotracer uptake on 18F-fluciclovine PET/CT. Left neck core needle biopsy confirmed high-grade, poorly differentiated carcinoma with neuroendocrine features positive for synaptophysin and chromogranin, and negative for prostate markers.

Topics: Aged; Biological Transport; Carboxylic Acids; Cyclobutanes; Humans; Male; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant

A 66-year-old man was diagnosed with metastatic prostate cancer to the bones. The patient started Ra-dichloride (Xofigo) therapy in April 2019. Tc-MDP bone scan and F-fluciclovine (Axumin) PET/CT showed discordant but overall complementary findings that indicated disease progression after 5 doses of Xofigo therapy. The patient's prostate-specific antigen increased from 33.81 ng/mL at baseline before Xofigo therapy and up to 394.3 ng/mL after the fifth dose of Xofigo treatment. Because of disease progression, Xofigo therapy was discontinued.

Topics: Aged; Bone and Bones; Carboxylic Acids; Cyclobutanes; Humans; Male; Neoplasm Metastasis; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Radium

trans-1-Amino-3-[(18)F]fluorocyclobutanecarboxylic acid ([(18)F]fluciclovine, also known as anti-[(18)F]FACBC), is a tracer for positron emission tomography (PET) imaging for detection of tumors such as prostate cancer (PCa). Our previous study showed that ASCT2 (Na(+)-dependent amino acid transporter (AAT)) mediates fluciclovine uptake in androgen-dependent PCa cells; its expression is influenced by androgen, a key hormone in the progression of primary PCa and castration-resistant prostate cancer (CRPC). In this study, we investigated the uptake mechanisms and feasibility of [(18)F]fluciclovine for CRPC in the androgen-dependent PCa cell line LNCaP and LNCaP-derivatives LNCaP-SF and LN-REC4.. LNCaP-SF was established after long-term cultivation of LNCaP in steroid-free conditions, and LN-Pre and LN-REC4 were established from LNCaP inoculated in intact and castrated severe combined immunodeficient mice, respectively. Uptake and competitive inhibition experiments were performed with trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid ([(14)C]fluciclovine) to characterize the involvement of AATs in androgen-dependent PCa (LNCaP and LN-Pre) and CRPC-like (LNCaP-SF and LN-REC4) cell lines. AAT expression was analyzed by Western blotting, and [(14)C]fluciclovine uptake in androgen-dependent PCa and CRPC-like cell lines were investigated in the presence or absence of dihydrotestosterone (DHT).. The contribution of Na(+)-dependent AATs to [(14)C]fluciclovine uptake in all cell lines was 88-98%, and [(14)C]fluciclovine uptake was strongly inhibited by L-glutamine and L-serine, the substrates for Na(+)-dependent alanine-serine-cysteine (system ASC) AATs, in the presence of Na(+). DHT enhanced ASCT2 expression in LNCaP, LN-Pre, and LN-REC4, but not in LNCaP-SF, and the responses of ASCT2 expression to DHT correlated with [(14)C]fluciclovine uptake.. System ASC, especially ASCT2, could play a major role in [(14)C]fluciclovine uptake into CRPC-like and androgen-dependent PCa cells, suggesting [(18)F]fluciclovine-PET is applicable to the detection of CRPC as well as androgen-dependent PCa.. [(18)F]fluciclovine-PET may be applied for the detection of CRPC.. [(18)F]fluciclovine-PET may permit early intervention for CRPC treatment.

Topics: Amino Acid Transport System ASC; Androgens; Animals; Binding, Competitive; Biological Transport; Carboxylic Acids; Cell Line, Tumor; Cyclobutanes; Dihydrotestosterone; Feasibility Studies; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Minor Histocompatibility Antigens; Prostatic Neoplasms, Castration-Resistant

Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18) F]FACBC) are used for visualization of prostate cancer. We examined the effect of androgen on the expression of amino acid transporters related to anti-[(18)F]FACBC transport and uptake of trans-1-amino-3-fluoro-[1-(14)C]cyclobutanecarboxylic acid (anti-[(14)C]FACBC).. Expression of amino acid transporters and uptake of anti-[(14)C]FACBC in androgen receptor (AR)-positive LNCaP and AR-negative DU145 human prostate cancer cells cultured with/without 5α-dihydrotestosterone (DHT) and the effect of bicalutamide, an AR antagonist, on DHT-associated changes were investigated.. DHT stimulated the expression of amino acid transporters ASCT2, SNAT5, 4F2 heavy chain, and LAT3 in LNCaP but not in DU145 cells. Anti-[(14)C]FACBC uptake was enhanced, in a DHT-dependent manner, in LNCaP cells only.. DHT enhanced the expression of ASCT2, the transporter responsible for anti-[(18)F]FACBC uptake, thereby increasing anti-[(14)C]FACBC uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to the distinct anti-[(18)F]FACBC accumulation pattern in prostate cancer.

Topics: Amino Acid Transport Systems; Androgens; Anilides; Carboxylic Acids; Cell Line, Tumor; Cyclobutanes; Dihydrotestosterone; Fluorine Radioisotopes; Gene Expression Regulation, Neoplastic; Humans; Male; Nitriles; Prostatic Neoplasms, Castration-Resistant; Radioactive Tracers; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Androgen; Tosyl Compounds