Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs

Abstract

Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids. The tumor imaging features of this last class of radiotracers mirror the upregulation of transmembrane amino acid transport that is necessary in carcinomas because of increased amino acid use for energy requirements and protein synthesis. Natural and synthetic amino acids radiolabeled for PET imaging have been investigated in prostate cancer patients. Early work with naturally occurring amino acid-derived radiotracers, such as L-11 C-methionine and L-1-11 C-5-hydroxytryptophan, demonstrated promising results, including greater sensitivity than 18 F-FDG for intraprostatic and extraprostatic cancer detection. However, limitations with naturally occurring amino acid-derived compounds, including metabolism of the radiotracer itself, led to the development of synthetic amino acid radiotracers, which are not metabolized and therefore more accurately reflect transmembrane amino acid transport. Of the synthetic amino acid-derived PET radiotracers, anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid ( 18 F-FACBC or 18 F-fluciclovine) has undergone the most promising translation to human use, including the availability of simplified radiosynthesis. Several studies have indicated advantageous biodistribution in the abdomen and pelvis with little renal excretion and bladder activity-characteristics beneficial for prostate cancer imaging. Studies have demonstrated improved lesion detection and diagnostic performance of 18 F-fluciclovine in comparison with conventional imaging, especially for recurrent prostate cancer, although issues with nonspecific uptake limit the potential role of 18 F-fluciclovine in the diagnosis of primary prostate cancer. Although work is ongoing, recently published intrapatient comparisons of 18 F-fluciclovine with 11 C-choline reported higher overall diagnostic performance of the former, especially for the detection of disease relapse. This review is aimed at providing a detailed overview of amino acid-derived PET compounds that have been studied for use in prostate cancer imaging.

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

“…Physicians may find it helpful to be aware of six key features of PET/CT with 18 F-fluciclovine. First, as a radiolabeled synthetic amino acid, 18 F-fluciclovine targets the amino acid transporters ASCT2 and LAT1 on cell surfaces [11,12]. ese transporters are overexpressed in prostate cancer and certain other malignancies and are ubiquitous throughout the body.…”

Radiotheranostics in Prostate Cancer: Introduction and Overview

“…Over the past few years, there have been major exciting developments in the synthesis and evaluation of PET radiotracers based on other biologic targets in prostate cancer. David Schuster from Emory University in Atlanta is the lead author on an article on the use of radiolabeled amino acids, in particular, anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid (fluciclovine), which received approval from the U.S. Food and Drug administration on May 27, 2016, for PET imaging in men with biochemical recurrence after definitive treatment for primary prostate cancer (11). The 4-author team of investigators from Germany, Japan, and Stanford present the next paper, which is on the potential clinical utility of radiotracers targeted to the gastrin-releasing peptide receptors (12).…”

Positron Emission Tomography Imaging of Prostate Cancer with Ga-68-Labeled Gastrin-Releasing Peptide Receptor Agonist BBN7–14 and Antagonist RM26

“…The classical 2-deoxy-2- 18 F-fluoro- d -glucose ( 18 F-FDG) has been used for evaluating late-stage or recurrent PCa but is not particularly avid. 8,9 Other promising agents targeting metabolites such as fatty acids and amino acids (e.g., 11 C- and 18 F-choline, 11 C-acetate, and 18 F-FACBC) have been further introduced 3,10 as well as agents targeting specific PCa antigens such as prostate-specific membrane antigen (PSMA). 11,12 These tracers are proven beneficial for recurrent PC diagnosis and staging.…”