Abstract
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Objectives The purpose is to test tumor specificity and gather preliminary biodistribution data on a new Tc99m labeled PSMA targeting tracer. RBI1033 is a high affinity 2-5A ligand which exhibits picomolar affinity toward PSMA. We have previously demonstrated that high affinity NIR fluorescent PSMA ligands can be designed by replacing the 2-5A nucleic acid moiety in RBI1033 with negatively charged amino acid residues such as glutamate. We continued the tracer development by replacing the NIR fluorophore with a N3S1 chelate for Tc99m.
Methods The peptide based tracer is synthesized using standard Fmoc solid phase peptide synthesis. The N3S1 chelate consists of gly-gly-gly-cys residues at the end of the peptide sequence. Affinity of the unlabeled ligand was measured with competitive binding assay using PC3-PIP cells. Tc99m labeling was performed at 100C for 1 hour. After SepPak cartridge purification, the labeled tracer was injected IV into two mice bearing PC3-PIP (PSMA+) and PC3-flu (PSMA-) xenographs. Whole body mouse SPECT/CT images were obtained at 4 hours using a 22-pinhole collimator insert developed in-house for clinical SPECT/CT detectors. At 5 hours, the mice were euthanized and biodistribution was measured.
Results The unlabeled peptide ligand demonstrated IC50 of 1.4nM while IC50 of ZJ24 in the same experiment was 5.1nM. Labeling efficiency of Tc99m was 95% by TLC. At four hours post injection, most injected tracer had been renally excreted to the bladder. On the 4 hour images, there was significant uptake in the tumor and renal parenchyma with minimal activity in the liver and bowel. At 5 hours post injection, the average PC3-PIP:PC3-flu ratio was 120:1. There was consistent renal uptake of 146%ID/g and 147%ID/g respectively in each mice. Minimal thyroid activity of 4.3%ID/g and 4.1%ID/g was noted.
Conclusions Tc99m labeled PSMA targeting tracer derived from RBI1033 demonstrated promising tumor targeting in this prelimnary biodistribution study.
Research Support DoD W81XWH-10-1-021