203Pb-labeled alpha-melanocyte-stimulating hormone peptide as an imaging probe for melanoma detection.

Abstract

UNLABELLED:

Peptide-targeted alpha-therapy with 7.4 MBq of (212)Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13) ((212)Pb-DOTA-Re(Arg(11))CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient-specific dosimetry and to monitor the tumor response to (212)Pb-DOTA-Re(Arg(11))CCMSH therapy. The purpose of this study was to evaluate the potential of (203)Pb-DOTA-Re(Arg(11))CCMSH as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH.

METHODS:

DOTA-Re(Arg(11))CCMSH was labeled with (203)Pb in 0.5 M NH(4)OAc buffer at pH 5.4. The internalization and efflux of (203)Pb-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of (203)Pb-DOTA-Re(Arg(11))CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with (203)Pb-DOTA-Re(Arg(11))CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection.

RESULTS:

(203)Pb-DOTA-Re(Arg(11))CCMSH was easily prepared in NH(4)OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). (203)Pb-DOTA-Re(Arg(11))CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of (203)Pb-DOTA-Re(Arg(11))CCMSH activity internalized after a 20-min incubation at 25 degrees C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a biodistribution pattern similar to that of (212)Pb-DOTA-Re(Arg(11))CCMSH in B16/F1 melanoma-bearing mice. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor uptake of 12.00+/-3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43+/-1.12 %ID/g at 48 h after injection. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of (203)Pb-DOTA-Re(Arg(11))CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. (203)Pb showed 1.6-mm SPECT resolution, which was comparable to (99m)Tc. Melanoma lesions were visualized through SPECT/CT images of (203)Pb-DOTA-Re(Arg(11))CCMSH at 2 h after injection.

CONCLUSION:

(203)Pb-DOTA-Re(Arg(11))CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH melanoma treatment.

• Authors: Yubin Miao, Said D Figueroa, Darrell R Fisher, Herbert A Moore, Richard F Testa, Timothy J Hoffman, Thomas P Quinn
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 49 Issue 5 Pg. 823-9 (May 2008) ISSN: 0161-5505 [Print] United States
• PMID: 18413404 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ac-Cys-Cys-Glu-His-D-Phe-Arg-Trp-Cys-Lys-Pro-Val-NH2
• Heterocyclic Compounds, 1-Ring
• Lead Radioisotopes
• Organotechnetium Compounds
• Peptide Fragments
• Receptor, Melanocortin, Type 1
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• alpha-MSH

Topics

• Amino Acid Sequence
• Animals
• Cell Line, Tumor
• Heterocyclic Compounds, 1-Ring (chemistry)
• Lead Radioisotopes
• Melanoma (diagnostic imaging, metabolism)
• Mice
• Organotechnetium Compounds
• Peptide Fragments (chemistry)
• Phantoms, Imaging
• Receptor, Melanocortin, Type 1 (metabolism)
• Tomography, Emission-Computed, Single-Photon (methods)
• alpha-MSH (chemistry, metabolism)