Radiology, Johns Hopkins University School of Medicine.
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 as well as 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 PC3 PSMA+ and PSMA- xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0.
RESULTS: DCFPyL displays a Ki value of 1.1 ± 0.1 nM 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/mu mol, n = 3). In an immunocompromised mouse model [18F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 h post-injection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PIP tumor, with a ratio of 358:1 of uptake within PIP to PSMA- PC3 flu tumor placed in the opposite flank. At or after 1 h post-injection, minimal non-target 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.
Written by:
Chen Y, Pullambhatla M, Byun Y, Foss CA, Nimmagadda S, Senthamizhchelvan S, Sgouros G, Mease RC, Pomper MG. Are you the author?
Reference: Clin Cancer Res. 2011 Oct 31. Epub ahead of print.
PubMed Abstract
PMID: 22042970
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