Initial Evaluation of [(18)F]DCFPyL for Prostate-Specific Membrane Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer

Abstract

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 [(18)F]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 (SUVmax up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [(18)F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi).

Conclusions: [(18)F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [(18)F]DCFPyL is similar to that from other PET radiotracers.

Fig. 1

Chemical structure of [¹⁸F]DCFPyL.

Fig. 2

Maximum intensity projection (MIP) PET image sequence in patient # 3. This patient demonstrated physiologic tracer uptake in the salivary glands, lacrimal glands, kidneys, liver, spleen, small intestine, and urinary excretion. There was uptake also in a histologically confirmed metastatic lesion involving the rectal wall.

Fig. 3

Time-activity curves in selected organs expressed as percent of injected dose per gram tissue (%ID/g) as a function of time (in minutes) post-injection. Organs of low and high radiotracer uptake are shown in the left set and right set of time-activity curves, respectively.

Fig. 4

Maximum intensity (MIP) PET image sequence in subject # 4. This patient demonstrated radiotracer binding in a large number of metastatic lesions involving multiple bones and lymph nodes. Physiologic biodistribution was the same as in the patient with minimal disease shown in Fig. 2.

Fig. 5

Average blood activity, plasma activity, and red cell activity of [¹⁸F]DCFPyL measured in nine subjects at 25, 86, and 150 min post-radiotracer administration.

Fig. 6

HPLC curves of the plasma radiotracer (“radioactivity”) in a subject at 34 and 173 min post-injection in comparison with the reference standard ligand (“UV”).

Fig. 7

Time course of tumor uptake values and tumor-to-background ratios. The time sequence of tumor uptake is expressed in SUV_max normalized to lean body mass (left upper corner). Tumor-to-blood ratios (T:B), tumor-to-muscle (T:M) ratios and tumor-to-liver (T:L) ratios are expressed in tumor SUV_max/reference tissue SUV_mean. The graphs show separately the average results from prostate bed lesions, lymph node metastases, and bone metastases (the hottest lesions from each patient were selected for this analysis, up to five lesions per patient).