posted on 2016-04-14, 00:00authored bySangeeta 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.