Positron emission tomography imaging of prostate cancer

Abstract

Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Positron emission tomography (PET), a non-invasive, sensitive, and quantitative imaging technique, can facilitate personalized management of PCa patients. There are two critical needs for PET imaging of PCa, early detection of primary lesions and accurate imaging of PCa bone metastasis, the predominant cause of death in PCa. Because the most widely used PET tracer in the clinic, (18)F-fluoro-2-deoxy-2-D-glucose ((18)F-FDG), does not meet these needs, a wide variety of PET tracers have been developed for PCa imaging that span an enormous size range from small molecules to intact antibodies. In this review, we will first summarize small-molecule-based PET tracers for PCa imaging, which measure certain biological events, such as cell membrane metabolism, fatty acid synthesis, and receptor expression. Next, we will discuss radiolabeled amino acid derivatives (e.g. methionine, leucine, tryptophan, and cysteine analogs), which are primarily based on the increased amino acid transport of PCa cells. Peptide-based tracers for PET imaging of PCa, mostly based on the bombesin peptide and its derivatives which bind to the gastrin-releasing peptide receptor, will then be presented in detail. We will also cover radiolabeled antibodies and antibody fragments (e.g. diabodies and minibodies) for PET imaging of PCa, targeting integrin alpha(v)beta(3), EphA2, the epidermal growth factor receptor, or the prostate stem cell antigen. Lastly, we will identify future directions for the development of novel PET tracers for PCa imaging, which may eventually lead to personalized management of PCa patients.

Fig. 1

Representative small molecule-based PET tracers for PCa imaging

Fig. 2

Representative radiolabeled amino acid derivatives for PET imaging of PCa

Fig. 3

PET imaging of PCa with ¹⁸F-FACBC. Axial PET (a) and PET/CT (b) images of a PCa patient, after injection with ¹⁸F-FACBC, revealed intense activity in the left external iliac node (black arrow in a). SPECT/CT with ¹¹¹In-capromab-pendetide (c & d) exhibited no significant radioactivity in this region (white arrow in c). Adapted from (Schuster et al. 2007)

Fig. 4

Serial PET images of mice bearing both PSMA-positive and PSMA-negative tumors after intravenous injection of ¹⁸F-DCFBC. L: Liver; K: kidney; B: bladder. Adapted from (Mease et al. 2008)

Fig. 5

Chemical structures of BBN (a) and its truncated derivative, BBN(7–14) (b)

Fig. 6

PET imaging of GRPR expression in PCa models. (a) Left: A coronal PET image of a PC-3 and CWR22 tumor-bearing mouse at 1 hour post-injection of ⁶⁴Cu-DOTA-[Lys³]BBN. Right: Digital autoradiograph of the mouse tissue section containing the tumors. (b) Decay-corrected whole-body coronal PET images of PC-3 tumor-bearing mice at 30 minutes post-injection of ¹⁸F-FB-BBN-RGD, ¹⁸F-BBN, or ¹⁸F-RGD. Tumors are indicated by arrowheads. Adapted from (Chen et al. 2004; Li et al. 2008)

Fig. 7

Quantitative PET imaging of EGFR expression in various tumor models including PCa. (a) Small-animal PET images of seven xenograft tumor models at 48 hours post-injection of ⁶⁴Cu-DOTA-cetuximab. Decay-corrected whole body coronal images are shown and the tumors are indicated by arrowheads. (b) Correlation of EGFR expression level (measured by Western blotting) and the %ID/g values (measured by microPET scans) of different tumors at 48 hours post-injection. Adapted from (Cai et al. 2007a)

Fig. 8

PET imaging of PSCA expression with engineered antibody fragments. (a) Serial coronal small-animal PET projections of a mouse bearing a PCa xenograft (indicated by “+”) injected with a ¹²⁴I-labeled anti-PSCA minibody. B: bladder. (b) Serial coronal small-animal PET images of PCa tumor-bearing mice after administration of a ¹²⁴I-labeled anti-PSCA diabody. +: PSCA-positive tumor;−: PSCA-negative tumor. Adapted from (Leyton et al. 2008a; Leyton et al. 2008b)