Imaging of Melanoma Using 64Cu− and 86Y−DOTA−ReCCMSH(Arg11), a Cyclized Peptide Analogue of α-MSH

Paul McQuade,† Yubin Miao,‡ Jeongsoo Yoo,† Thomas P. Quinn,‡ Michael J. Welch,†§ and Jason S. Lewis*†§
Division of Radiological Sciences, Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110, and Department of Biochemistry, University of MissouriColumbia, Columbia, Missouri 65212
J. Med. Chem., 2005, 48 (8), pp 2985–2992
DOI: 10.1021/jm0490282
Publication Date (Web): March 8, 2005
Copyright © 2005 American Chemical Society
†

 Mallinckrodt Institute of Radiology, Washington University School of Medicine.

,
‡

 University of MissouriColumbia.

,
§

 Alvin J. Siteman Cancer Center, Washington University School of Medicine.

,
*

 Corresponding author. Phone:  (314) 362−4696. Fax:  (314) 362−9940. E-mail:  LewisJas@mir.wustl.edu.

Abstract

Abstract Image

Early detection of melanoma is essential, since a patient's prognosis with metastatic melanoma is poor. Previous studies showed that 111In−DOTA−ReCCMSH(Arg11), a cyclic analogue of α-melanocyte stimulating hormone (α-MSH), exhibited high tumor concentration and rapid clearance from nontarget tissue. The goal of this current study was to label DOTA−ReCCMSH(Arg11) with β+-emitting radionuclides, to determine if the high sensitivity of positron emission tomography (PET) imaging would aid in the detection of malignant melanoma. DOTA−ReCCMSH(Arg11) was labeled with 64Cu and 86Y. Biodistribution and small animal PET imaging were carried out in mice implanted with B16/F1 murine melanoma tumor and compared with data obtained in the same animal model with [18F]FDG. In both cases a subset of animals were co-injected with 20 μg of DOTA−ReCCMSH(Arg11) to determine if tumor concentration was receptor mediated. Tumor concentration for both the 86Y- and 64Cu-complexes reached a maximum at 30 min, while coadministering 20 μg of unlabeled complex reduced tumor uptake significantly. Nontarget organ concentration was considerably lower with 86Y−DOTA−ReCCMSH(Arg11) than its 64Cu analogue, except in the kidneys, where the 64Cu complex had lower accumulation at all time points. Small animal PET images for both complexes showed the tumor could be visualized after 30 min, with the standardized uptake value (SUV) analysis following a similar trend as the biodistribution data. The data obtained suggests that DOTA−ReCCMSH(Arg11), when labeled with β+-emitting radionuclides, has the potential for early detection of malignant melanoma by exploiting the sensitivity and high resolution of PET.

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History

  • Published In Issue April 21, 2005
  • Received November 30, 2004

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