Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

Miao, Yubin; Fisher, Darrell R.; Quinn, Thomas P.

doi:10.1016/j.nucmedbio.2006.06.005

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 723-733, August 2006

Reducing renal uptake of ⁹⁰Y- and ¹⁷⁷Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

Yubin Miao
- Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211, USA
- Department of Dermatology, University of Missouri-Columbia, Columbia, MO 65211, USA
- Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201, USA
- Corresponding author. Departments of Internal Medicine and Dermatology, A051 VA Research Service, University of Missouri-Columbia, Columbia, MO 65211, USA. Tel.: +1 573 814 6000x3681; fax: +1 573 814 6551.
- Current address: 2502 Marble NE, MSC09 5360, College of Pharmacy, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA. Tel.: +1 505 925 4437; fax: +1 505 272 6749.
Darrell R. Fisher
- Pacific Northwest National Laboratory, Richland, WA 99352, USA
Thomas P. Quinn
- Harry S. Truman Memorial Veteran Hospital, Columbia, MO 65201, USA
- Department of Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA
- Department of Radiology, University of Missouri-Columbia, Columbia, MO 65211, USA

Received 2 May 2006; received in revised form 2 June 2006; accepted 15 June 2006.

Abstract

Objective

The purpose of this study was to improve the tumor-to-kidney uptake ratios of ⁹⁰Y- and ¹⁷⁷Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys^3,4,10, d-Phe⁷, Arg¹¹]α-melanocyte stimulating hormone_3–13 {DOTA-Re(Arg¹¹)CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence.

Methods

A new peptide of DOTA-Re(Glu², Arg¹¹)CCMSH was designed, synthesized and labeled with ⁹⁰Y and ¹⁷⁷Lu. Pharmacokinetics of ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice.

Results

⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH exhibited significantly (P<.05) less renal uptake values than ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH were 28.16% and 28.81% of those of ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH, respectively, at 4 h postinjection. ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH displayed higher tumor-to-kidney uptake ratios than ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH was 2.28 and 1.69 times of ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Arg¹¹)CCMSH, respectively, at 4 h postinjection. The ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH activity accumulation was low in normal organs except for kidney.

Conclusions

Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of ⁹⁰Y- and ¹⁷⁷Lu-DOTA-Re(Glu², Arg¹¹)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

Keywords: Alpha-melanocyte stimulating hormone, Radiolabeled peptide, Renal uptake, Radionuclide therapy of melanoma