Molecular Imaging of Prostate Cancer: Radiopharmaceuticals for Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT)

Abstract

Prostate cancer is characterized by evolution from a clinically localized hormone-naive state in the prostate gland to an eventually castration-resistant metastatic state. Clinical imaging tools employed in the diagnosis of prostate cancer include transrectal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and bone scans. Unfortunately, the likelihood of disease detection with these modalities is low. The structural imaging techniques such as CT and MRI provide details about the anatomy and anatomical relations such as size, local invasions, tumor borders, and anatomical distortions. In contrast, molecular imaging based on single-photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals is a type of medical imaging that provides detailed pictures of what is happening inside the body noninvasively at the molecular and cellular level and offers unique insights into the human body that enable physicians to personalize patient care. The molecular imaging radiopharmaceuticals target specifically biologically relevant molecules such as enzymes involved in the metabolism of glucose and fatty acids, receptors such as androgen receptors (AR), and antigens such as prostate-specific membrane antigen (PSMA). The current Food and Drug Administration (FDA)-approved molecular imaging radiopharmaceuticals include 99mTc-labeled bone imaging agents and 111In-labeled anti-PSMA antibody (ProstaScint™) for SPECT and [18F]fluorodeoxyglucose, [18F]sodium fluoride (NaF), and [11C]choline (CH) for PET. Emerging agents under clinical development include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as other small molecules more specifically targeting prostate cancer biomarkers including AR and PSMA. In the last 5 years, several small-molecule PSMA inhibitors labeled with 123I or 99mTc (for SPECT) and 18F or 68Ga (for PET) have been evaluated in phase I and II clinical studies and show significant diagnostic potential for molecular imaging studies of prostate cancer. As the management of prostate cancer becomes more personalized and new treatments become available, there is increasing clinical demand for molecular imaging for prostate cancer diagnosis. In this chapter, we have highlighted a great number and variety of emerging molecular imaging agents for prostate cancer diagnosis.