PSMA‐targeted imaging of prostate cancer: the best is yet to come (2016)

In recent years there has been increasing interest in imaging recurrent or metastatic prostate cancer with positron-emission tomography (PET) radiotracers targeting prostate-specific membrane antigen (PSMA 1). The majority of this work has been performed using urea-based small molecules labelled with gallium-68 (68Ga). Within this class of radiotracers, 68Ga-PSMA-11 (also known as 68Ga-PSMA-HBED-CC) has been the most widely studied. In this month's edition of BJUI, van Leeuwen et al. 2 report on the clinical utility of 68Ga-PSMA-11 PET/CT in men with rising PSA levels after radical prostatectomy being considered for salvage radiation therapy. In their study, 70 patients with negative conventional imaging findings and a median PSA of 0.2 ng/mL (all <1 ng/mL) were imaged with 68Ga-PSMA-11 PET/CT prior to initiating treatment. On PSMA-targeted PET/CT, 53 lesions were detected in 38 (54%) patients. Perhaps most significant among their findings was that 28.6% of men had radiotracer uptake outside of the prostatic fossa leading to a major change in clinical management. In total, these data demonstrate the great potential of PSMA-targeted imaging, particularly in men with biochemically recurrent prostate cancer. While a great deal of encouraging data with 68Ga-PSMA-11 has appeared in the medical literature, it is worth noting that several other small molecules that offer potential advantages over this agent have seen early clinical development. For example, PSMA-617 makes use of the DOTA chelation moiety in place of HBED-CC, allowing for a scaffold that can accommodate both diagnostic 68Ga and therapeutic lutetium-177 (177Lu) 3. Additionally, our group has focused on fluorine-18 (18F)-labelled urea-based small molecules targeting PSMA, most recently 18F-DCFPyL 4. 18F-labelled small molecules offer several potential advantages over those labelled with 68Ga. These include more favourable dosimetry allowing for higher injected radiotracer doses and lower-energy emitted positrons that have shorter path lengths to annihilation and therefore higher intrinsic spatial resolution 5. Notably, a recent direct comparison of 68Ga-PSMA-11 and 18F-DCFPyL performed by Dietlein et al. 6 seems to confirm these advantages, having observed a higher rate of lesion detection as well as superior mean tumour-to-background ratios with the radiofluorinated compound. An additional advantage of 18F-labelled compounds is related to their longer half-life for radionuclide decay (109 vs 68 min for 68Ga). Given this difference, agents incorporating 68Ga typically require an on-site generator for radiotracer production, whereas 18F-based radiotracers can be produced en masse at a central site with a cyclotron and then delivered to remote locations via pre-existing distribution infrastructure (e.g. PETNET in the USA). Table 1 summarizes several relevant differences in the physical properties of 68Ga and 18F. In summary, these are exceptionally exciting times for the study of PSMA-targeted imaging of prostate cancer. With continued radiotracer development and accompanying well-designed clinical trials, there is no doubt we can drastically improve the care of men with prostate cancer. Martin G. Pomper is a co-inventor on a US Patent covering 18F-DCFPyL and, as such, is entitled to a portion of any licensing fees and royalties generated by this technology. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The remaining authors have no conflicts of interest to declare.