Purpose Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [¹⁸F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Procedures Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. Results No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUV_max up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [¹⁸F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi). Conclusions [¹⁸F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [¹⁸F]DCFPyL is similar to that from other PET radiotracers.

Purpose: We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[¹⁸F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [¹⁸F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors. Experimental Design: [¹⁸F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[¹⁸F]fluoronicotinic acid tetrafluorophenyl ester ([¹⁸F]F-Py-TFP) for introduction of ¹⁸F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA- PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0. Results: DCFPyL displays a K_i value of 1.1 ± 0.1 nmol/L for PSMA. [¹⁸F]DCFPyL was produced in radiochemical yields of 36%–53% (decay corrected) and specific radioactivities of 340–480 Ci/mmol (12.6–17.8 GBq/μmol, n = 3). In an immunocompromised mouse model [¹⁸F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA− PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [¹⁸F]DCFPyL was observed. The bladder wall is the dose-limiting organ. Conclusions: These data suggest [¹⁸F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues. Clin Cancer Res; 17(24); 7645–53. ©2011 AACR.

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high‐throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full‐blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging—particularly when combined with liquid biopsy for screening purposes—promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near‐term challenges and opportunities in oncology.

Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-¹⁸F-fluorobenzyl-l-cysteine (¹⁸F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of ¹⁸F-DCFBC in men with metastatic PCa. Methods: Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of ¹⁸F-DCFBC. Serial PET was performed until 2 h after administration. Time–activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results: Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radioactivity (μGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 μSv/MBq (mean ± SD). Conclusion: Although further studies are needed for validation, our findings demonstrate the potential of ¹⁸F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for ¹⁸F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as ¹⁸F-FDG.