Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex


Evaluation of Tricine and EDDA as Co-ligands for 99mTc-Labeled HYNIC-MSH Analogs for Melanoma Imaging

Author(s): Maria Fernanda Garcia, Xiuli Zhang, Fabio Gallazzi, Marcelo Fernandez, Maria Moreno, Juan Pablo Gambini, Williams Porcal, Pablo Cabral, Thomas P. Quinn.

Graphical Abstract:


Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with 99m via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with 99mTc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that 99mTc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than 99mTc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of 99mTc labeled lactam cyclized MSH molecules as melanoma imaging agents.

Keywords: HYNIC, melanoma imaging, MSH analogs, 99mTc.

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Article Details

Page: [122 - 130]
Pages: 9
DOI: 10.2174/1871520614666140825123150