PET imaging in prostate cancer: focus on prostate-specific membrane antigen

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. Positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease, detection of metastatic lesions and, ultimately, for predicting the aggressiveness of disease. Prostate-specific membrane antigen (PSMA) is a well-characterized imaging biomarker of PCa. Because PSMA levels are directly related to androgen independence, metastasis and progression, PSMA could prove an important target for the development of new radiopharmaceuticals for PET. Preclinical data for new PSMA-based radiotracers are discussed and include new (89)Zr- and (64)Cu-labeled anti-PSMA antibodies and antibody fragments, (64)Cu-labeled aptamers, and (11)C-, (18)F-, (68)Ga-, (64)Cu-, and (86)Y-labeled low molecular weight inhibitors of PSMA. Several of these agents, namely (68)Ga- HBED-CC conjugate 15, (18)F-DCFBC 8, and BAY1075553 are particularly promising, each having detected sites of PCa in initial clinical studies. These early clinical results suggest that PET/CT using PSMA-targeted agents, especially with compounds of low molecular weight, will make valuable contributions to the management of PCa.

Fig. 1

PET agents derived from 2-PMPA.

Fig. 2

Cysteine-glutamate- and lysine-glutamate-urea-based PET radiotracers.

Fig. 3

Radiometal-labeled lysine-glutamate-urea PET radiotracers.

Fig. 4

⁶⁸Ga-labeled HBED-CC conjugates of lysine-glutamate-urea.

Fig. 5

¹⁸F-labeled DUPA analogs.

Fig. 6

¹⁸F-DCFBC PET, CT and bone scan of a patient with suspected bone metastases in the sacrum (A and B) and right and left ischium (C and D). Bone metastasis in the sacrum is located by the black arrow in A (PET) and confirmed by the arrow in E (bone scan). Bone metastasis in the right ischium is located by the bold arrow in C (PET), and E (bone scan). A smaller focus of radioactivity in the left ischium is located by the black arrow in C (PET), but is not visible on the bone scan. The arrow head in C and D denotes bladder radioactivity.

Fig. 7

¹⁸F-DCFBC PET and CT scans of a subcentimeter left common iliac lymph node. The lymph node is indicated by the bold arrow on the PET image. The lymph node is clearly discernible from urinary radioactivity in the left ureter (thin arrows on images).