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Radionuclide-based Diagnosis and Therapy of Prostate Cancer
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Sven-Erik Strand, Mohamed Altai, Joanna Strand, David Ulmert
Amino acids are essential to cell metabolism and growth. Several amino acid transporter systems are overexpressed in PCa. Anti-1-amino-3-[18F]Flurocyclobutane-1-carboxylic acid (18F-fluciclovine-FACBC) is a non-naturally occurring amino acid, and its transport is primarily mediated by sodium-dependent amino acid transporters. Because the amino acid transporters that are most involved in 18F-fluciclovine transport mediate influx and efflux of amino acids, washout of the radiotracer occurs over time. The specificity of 18F-fluciclovine for PCa relies on altered metabolic pathways overexpressed in PCa. Studies have shown a detection rate of 40 per cent for patients with biochemical recurrence and a PSA level of 0.79 ng/mL or less. Direct comparison between 18F-fluciclovine and 11C-choline PET/CT has demonstrated overall superior imaging performance for 18F-fluciclovine in biochemically recurrent PCa. A good overview of 18F-Fluciclovine is found in Parent and Schuster and colleagues [71].
Urinary Symptoms and Investigations
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Choline PET/CT using either 11C-choline or 18F-choline as the radiotracer have been increasingly used, especially in the assessment of metastatic disease in men with prostate cancer who have failed primary treatment and may be candidates for salvage therapy (Figure75.26). A new radiotracer for PET/CT, 18F-fluciclovine, was approved by the Food and Drug Administration (FDA) in May 2016 for the diagnosis of suspected prostate cancer recurrence after primary therapy.
Non-FDG radionuclide imaging and targeted therapies
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Luigi Aloj, Ferdia A Gallagher
Radiolabelled amino acids have been used in brain tumours for the differential diagnosis of brain tumours, delineation of tumour extent, differentiation between progression and recurrence, and for response monitoring (62). These agents can significantly enhance the diagnostic value of magnetic resonance imaging (MRI). Grey-matter uptake of amino acids is relatively low, whereas tumour cells have increased demand for amino acids due to high protein synthesis and proliferation. 11C-labelled methionine was the first tracer utilized in this category (63) and is currently used in several centres for identifying active tumour versus radionecrosis. The drawback of the use of 11C-methionine is its short half-life (20 min) and limited availability as discussed previously. Tracers labelled with the longer-lived 18F (109 minute half-life) have therefore gained interest for imaging glioma more recently. 18F-labelled fluoroethyl tyrosine (18F-FET) and fluorodihydroxyphenylalanine (18F-DOPA) are both L-amino acid transporter (LAT) substrates (64) which have been successfully utilized for imaging and detecting recurrent glioma and pituitary tumours and may be utilized for guiding biopsy and radiotherapy (65). An example of the use of 11C-L-methionine in glioma is shown in Figure 44.6. Amino acid transport/metabolism has also been targeted in tumours with lower glucose metabolic rates such as prostate cancer. Recently, an amino acid-derived PET radiotracer, anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC or 18F-fluciclovine) has undergone promising translation to human use and was approved by the FDA in 2016 for imaging patients with suspected recurrence of prostate cancer (66).
Addressing the need for more therapeutic options in neuroendocrine prostate cancer
Published in Expert Review of Anticancer Therapy, 2023
Jayson Kemble, Eugene D. Kwon, R. Jeffrey Karnes
PET/CT imaging has been shown to be superior to other imaging modalities for the detection of metastatic PC [38,39]. It provides an earlier depiction of disease and is capable of identifying recurrent PC at PSA <0.1 ng/ml [40]. PET/CT imaging can be divided into two categories, metabolic and marker targeted, both involving positron emitting radiolabels that can be detected through positron decay [41]. Metabolic PET/CT scans used in PC include 11-C Choline and 18-F Fluciclovine. 11-C Choline is a quaternary ammonium base that is metabolized into the phospholipid phosphatidylcholine and integrated into the cell membrane, with increased choline uptake suggestive of accelerated cell membrane proliferation [42,43]. 18-F Fluciclovine is an analog of levorotatory leucine and has the highest uptake in tissues that actively produce proteins or process amino acids, as seen in many carcinomas [44]. Marker targeted PET/CT imaging targets antigens preferentially expressed on PC cells such as PSMA, with 68 Ga-PSMA-11 being the first PSMA PET/CT approved by the FDA in December 2020. 68 Ga-PSMA PET has a high diagnostic yield for detecting pelvic lymph node and distant metastases in patients with biochemically recurrent PC, even at low PSA levels [45–52]. PSMA-PET/CT has a higher sensitivity and specificity in detecting PC bone metastases than non-PSMA PET scans [38]. Unfortunately, NEPC typically loses expression of PSMA, which can make detection with PSMA PET/CT scans difficult as known lesions may not have any PSMA uptake [53].
Piflufolastat F-18 (18F-DCFPyL) for PSMA PET imaging in prostate cancer
Published in Expert Review of Anticancer Therapy, 2022
Andrew F. Voter, Rudolf A. Werner, Kenneth J. Pienta, Michael A. Gorin, Martin G. Pomper, Lilja B. Solnes, Steven P. Rowe
Direct detection of malignant cells would allow for more sensitive imaging modalities since such modalities would not rely on morphologic changes to anatomic structures. To this end, a variety of imaging agents exploiting the overcharged metabolism of prostate cancer cells have been developed. The first, 11C-choline, incorporates into the cellular membranes of rapidly dividing cells. It is more sensitive for the detection of bony metastases than bone scintigraphy, especially at lower PSA levels, but remains quite insensitive with PSA levels lower than 2 ng/mL [13–15]. 18F-Fluciclovine, a lysine analog, is taken up by amino acid transporters upregulated in metabolically active metastases and has low excretion into the urinary system. While more sensitive than the non-PET imaging modalities, it too is limited by poor sensitivity at lower PSA levels [16–18]. Another radiotracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG), is used in a variety of non-prostate oncologic applications, but prostate cancer tends to have limited accumulation of FDG, possibly due to reduced reliance on glycolytic metabolism relative to other cancers. This has limited its use for imaging of prostate cancer [19], although there may be a role for FDG in the detection of metastatic castration-resistant prostate cancer with diminished PSMA expression [20].
Non-metastatic castration-resistant prostate cancer: current status and future directions
Published in Expert Review of Anticancer Therapy, 2020
Ruby Gupta, Iris Y Sheng, Pedro C. Barata, Jorge A. Garcia
18F-fluciclovine PET-CT was recently approved by FDA for the detection of metastatic disease in prostate cancer patients who had definitive treatment and now have a rising PSA [31]. It uses the increased activity of the ASCT 2 and LAT 1 amino acid transporters that are upregulated in prostate cancer [32,33]. The approval was based on two prospective studies comparing 18F-fluciclovine PET-CT with histopathology results and with 11C-choline PET in patients with biochemical recurrent prostate cancer [34–36]. These studies revealed that 18F-fluciclovine PET-CT performed much better in terms of the rate of lesion detection for patients with low, intermediate, and high PSA levels, with higher sensitivity than that noted for 11C-choline PET.