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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

The Effect of A Hexanoic Acid Linker Insertion on the Pharmacokinetics and Tumor Targeting Properties of the Melanoma Imaging Agent 99mTc-HYNIC-cycMSH

Author(s): Vania Teixeira, Marcelo Fernández, Natalia Oddone, Xiuli Zhang, Fabio Gallazzi, Hugo Cerecetto, Juan Pablo Gambini, Williams Porcal, Pablo Cabral* and Thomas P. Quinn

Volume 17, Issue 8, 2017

Page: [1144 - 1152] Pages: 9

DOI: 10.2174/1871520616666161206144414

Price: $65


Background: Lactam cyclized alpha-melanocyte stimulating hormone (α-MSH) analogues exhibit high stability and affinity for the MC1-R receptors over expressed in melanoma cells. Recently, we reported a novel 99mTc-HYNIC-cycMSH4-13 analogue with the HYNIC chelator directly attached to the lactam cyclized ring.

Objective: In this study we proposed the introduction of a 6-aminohexanoic acid (Ahx) linker between the HYNIC chelator and lactam cyclized peptide cycMSH4-13 to reduce steric hindrance and improve the melanoma targeting and imaging proprieties of the radiolabeled peptide.

Method: HYNIC-Ahx-cycMSH4-13 peptide was synthesized on an automated peptide synthesizer and displayed an IC50 of 0.3 nM using B16/F1 cells. The 99mTc/tricine radiolabeled peptide was examined for radiochemical purity, stability and cell binding. In vivo, biodistribution and planar gamma imaging studies were performed in B16/F1 melanoma tumor bearing C57BK mice.

Results: 99mTc-HYNIC-Ahx-cycMSH4-13 was obtained with a radiochemical purity >95%, was stable up to 24 h at room temperature and exhibited high binding and rapid internalization in B16/F1 cells. In vivo biodistribution studies showed a tumor uptake of 4.92 ± 0.92 % ID/g and 2.78 ± 1.48 % ID/g at 2 h and 4 h post injection, respectively. Whole-body clearance was rapid through urinary excretion. The melanoma tumors were clearly visualized by planar gamma imaging.

Conclusion: 99mTc-HYNIC-Ahx-cycMSH4-13was shown radiochemically stability and exhibited rapid and selective uptake in melanoma cells and tumors. Imaging studies yielded promising preclinical results, warranting further evaluation of 99mTc-HYNIC-cycMSH analogs as melanoma specific imaging agents.

Keywords: HYNIC, α-MSH, 99mTc, melanoma, Ahx, tumor.

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