Therapeutic efficacy of a 188Re-labeled alpha-melanocyte-stimulating hormone peptide analog in murine and human melanoma-bearing mouse models.

Abstract

UNLABELLED:

The purpose of this study was to examine the therapeutic efficacy of (188)Re-(Arg(11))[Cys(3,4,10),d-Phe(7)]alpha-melanocyte-stimulating hormone(3-13) (CCMSH) in the B16/F1 murine melanoma- and TXM13 human melanoma-bearing mouse models.

METHODS:

(Arg(11))CCMSH was synthesized and labeled with (188)Re to form (188)Re-(Arg(11))CCMSH. B16/F1 melanoma-bearing mice were administrated 7.4 MBq, 22.2 MBq, and 2 x 14.8 MBq of (188)Re-(Arg(11))CCMSH via the tail vein. TXM13 melanoma-bearing mice were separately injected with 22.2 MBq, 2 x 14.8 MBq, and 37.0 MBq of (188)Re-(Arg(11))CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls.

RESULTS:

In contrast to the untreated control group, (188)Re-(Arg(11))CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2 x 14.8 MBq of (188)Re-(Arg(11))CCMSH significantly extended the mean life of B16/F1 tumor mice (P < 0.05), whereas the mean life of TXM13 tumor mice was significantly prolonged after treatment with 22.2-MBq and 37.0- MBq doses of (188)Re-(Arg(11))CCMSH (P < 0.05). High-dose (188)Re-(Arg(11))CCMSH produced no observed normal tissue toxicity.

CONCLUSION:

The therapy study results revealed that (188)Re-(Arg(11))CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma- and TXM13 human melanoma-bearing mouse models. (188)Re-(Arg(11))CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

• Authors: Yubin Miao, Nellie K Owen, Darrell R Fisher, Timothy J Hoffman, Thomas P Quinn
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 46 Issue 1 Pg. 121-9 (Jan 2005) ISSN: 0161-5505 [Print] United States
• PMID: 15632042 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Radioisotopes
• Radiopharmaceuticals
• alpha-MSH
• Rhenium

Topics

• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Drug Delivery Systems (methods)
• Humans
• Melanoma (metabolism, radiotherapy)
• Metabolic Clearance Rate
• Mice
• Mice, Inbred C57BL
• Organ Specificity
• Radioisotopes (pharmacokinetics, therapeutic use)
• Radiopharmaceuticals (therapeutic use)
• Radiotherapy Dosage
• Rhenium (pharmacokinetics, therapeutic use)
• Survival Analysis
• Tissue Distribution
• Treatment Outcome
• alpha-MSH (pharmacokinetics, therapeutic use)