Comparison of two peptide radiotracers for prostate carcinoma targeting

Abstract

OBJECTIVES:Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid.METHODS:The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors.RESULTS:The radiochemical purity of both radiotracers was greater than 95%. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32% of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP-1 and the bombesin radiotracer primarily targeted the pancreas.CONCLUSION:Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.

Cell-Penetrating Peptides Derived from Animal Venoms and Toxins

“…Reportedly, bombesin binds with high affinity to the gastrin-releasing peptide receptor (GRPR) of target cells and the short C-terminal fragments (residues 7 to 14, WAVGHLMH-amide), sharing identity with gastrin-releasing peptide (GRP), was found to be crucial and sufficient for receptor binding, as well as the biological activity of bombesin-like peptides [ 118 ]. The bombesin/GRP receptor subtype 2 is known to be overexpressed in diverse cancer types, allowing the application of radiolabeled bombesin-like peptide analogs as tracers for the detection and/or treatment of G-protein-coupled receptor (GPCR)-positive tumors [ 121 , 122 ]. For instance, short bombesin-like peptide analogs with natural and non-natural amino acids have been synthesized and labeled with radionuclides (99 mTc, 111In, 90Y, 64Cu, 177Lu, 68Ga or 18F) and evaluated in vivo and in vitro in animal models and humans to detect GPCR-overexpressing tumors [ 121 , 123 ].…”

Peptides Identified Through Phage Display for Prostate Cancer Imaging and Therapy

“…Besides these imaging methods, many investigations have been conducted using diagnostic radiotracer specific for prostate cancer imaging. Based on phage-displayed peptide contrast agents, Faintuch et al compared two peptide radiotracers for prostate carcinoma targeting and imaging and demonstrated that peptide radiotracers are promising for prostate cancer imaging [20].…”