American Chemical Society
bc5b00679_si_001.pdf (346.75 kB)

Preclinical Comparative Study of 68Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA

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journal contribution
posted on 2016-04-14, 00:00 authored by Sangeeta Ray Banerjee, Zhengping Chen, Mrudula Pullambhatla, Ala Lisok, Jian Chen, Ronnie C. Mease, Martin G. Pomper
68Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: 68Ga-1, using DOTA-monoamide as the chelating agent; 68Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and 68Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC. The PSMA-targeting scaffold for all three agents utilized a similar Glu-urea-Lys-linker construct. Each radiotracer enabled visualization of PSMA+ PC3 PIP tumor, kidney, and urinary bladder as early as 15 min post-injection using small animal PET/computed tomography (PET/CT). 68Ga-2 demonstrated the fastest rate of clearance from all tissues in this series and displayed higher uptake in PSMA+ PC3 PIP tumor compared to 68Ga-1 at 1 h post-injection. There was no significant difference in PSMA+ PC3 PIP tumor uptake for the three agents at 2 and 3 h post-injection. 68Ga-DKFZ-PSMA-11 demonstrated the highest uptake and retention in normal tissues, including kidney, blood, spleen, and salivary glands and PSMA-negative PC3 flu tumors up to 3 h post-injection. In this preclinical evaluation 68Ga-2 had the most advantageous characteristics for PSMA-targeted PET imaging.