Tc-99m-labeled RGD-conjugated Alpha-melanocyte Stimulating Hormone Hybrid Peptides with Reduced Renal Uptake

Overview

Journal Amino Acids

Specialty Biochemistry

Date 2015 Jan 6

PMID 25557051

Citations 3

Authors

Jianquan Yang

Chien-An A Hu

Yubin Miao

Affiliations

Soon will be listed here.

Abstract

The purpose of this study was to examine whether the replacement of the positively-charged Lys or Arg linker with a neutral linker could reduce the renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), D-Phe(7), Arg(11)]α-MSH3-13 {(Arg(11))CCMSH} through the neutral βAla or Ahx {aminohexanoic acid} linker (replacing the Lys or Arg linker) to generate novel RGD-βAla-(Arg(11))CCMSH and RGD-Ahx-(Arg(11))CCMSH hybrid peptides. The receptor-binding affinity and cytotoxicity of RGD-βAla-(Arg(11))CCMSH and RGD-Ahx-(Arg(11))CCMSH were determined in B16/F1 melanoma cells. The melanoma targeting and imaging properties of (99m)Tc-RGD-βAla-(Arg(11))CCMSH and (99m)Tc-RGD-Ahx-(Arg(11))CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The replacement of the Lys or Arg linker with the βAla or Ahx linker retained nanomolar receptor-binding affinities and remarkable cytotoxicity of RGD-βAla-(Arg(11))CCMSH and RGD-Ahx-(Arg(11))CCMSH. The receptor-binding affinities of RGD-βAla-(Arg(11))CCMSH and RGD-Ahx-(Arg(11))CCMSH were 0.8 ± 0.05 and 1.3 ± 0.1 nM. Three-hour incubation with 0.1 µM of RGD-βAla-(Arg(11))CCMSH and RGD-Ahx-(Arg(11))CCMSH decreased the survival percentages of B16/F1 cells by 71 and 67 % as compared to the untreated control cells 5 days post the treatment. The replacement of the Arg linker with the βAla or Ahx linker reduced the non-specific renal uptake of (99m)Tc-RGD-βAla-(Arg(11))CCMSH and (99m)Tc-RGD-Ahx-(Arg(11))CCMSH by 62 and 61 % at 2 h post-injection. (99m)Tc-RGD-βAla-(Arg(11))CCMSH displayed higher melanoma uptake than (99m)Tc-RGD-Ahx-(Arg(11))CCMSH at 0.5, 2, 4, and 24 h post-injection. Enhanced tumor to kidney uptake ratio of (99m)Tc-RGD-βAla-(Arg(11))CCMSH warranted the further evaluation of (188)Re-labeled RGD-βAla-(Arg(11))CCMSH as a novel MC1 receptor-targeting therapeutic peptide for melanoma treatment in the future.

Citing Articles

Elevating theranostics: The emergence and promise of radiopharmaceutical cell-targeting heterodimers in human cancers.

Chambers C, Chitwood B, Smith C, Miao Y iRadiology. 2024; 2(2):128-155.

PMID: 38708130 PMC: 11067702. DOI: 10.1002/ird3.62.

Ga-DOTA-GGNle-CycMSH targets the melanocortin-1 receptor for melanoma imaging.

Yang J, Xu J, Gonzalez R, Lindner T, Kratochwil C, Miao Y Sci Transl Med. 2018; 10(466).

PMID: 30404861 PMC: 6383514. DOI: 10.1126/scitranslmed.aau4445.

PET and SPECT imaging of melanoma: the state of the art.

Wei W, Ehlerding E, Lan X, Luo Q, Cai W Eur J Nucl Med Mol Imaging. 2017; 45(1):132-150.

PMID: 29085965 PMC: 5700861. DOI: 10.1007/s00259-017-3839-5.

References

Rolleman E, Krenning E, van Gameren A, Bernard B, de Jong M . Uptake of [111In-DTPA0]octreotide in the rat kidney is inhibited by colchicine and not by fructose. J Nucl Med. 2004; 45(4):709-13. View

Miao Y, Owen N, Fisher D, Hoffman T, Quinn T . Therapeutic efficacy of a 188Re-labeled alpha-melanocyte-stimulating hormone peptide analog in murine and human melanoma-bearing mouse models. J Nucl Med. 2005; 46(1):121-9. View

Maack T, Johnson V, Kau S, Figueiredo J, Sigulem D . Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review. Kidney Int. 1979; 16(3):251-70. DOI: 10.1038/ki.1979.128. View

Froidevaux S, Calame-Christe M, Tanner H, Eberle A . Melanoma targeting with DOTA-alpha-melanocyte-stimulating hormone analogs: structural parameters affecting tumor uptake and kidney uptake. J Nucl Med. 2005; 46(5):887-95. View

Behe M, Kluge G, Becker W, Gotthardt M, Behr T . Use of polyglutamic acids to reduce uptake of radiometal-labeled minigastrin in the kidneys. J Nucl Med. 2005; 46(6):1012-5. View

Miao Y, Hylarides M, Fisher D, Shelton T, Moore H, Wester D . Melanoma therapy via peptide-targeted {alpha}-radiation. Clin Cancer Res. 2005; 11(15):5616-21. DOI: 10.1158/1078-0432.CCR-05-0619. View

de Jong M, Barone R, Krenning E, Bernard B, Melis M, Visser T . Megalin is essential for renal proximal tubule reabsorption of (111)In-DTPA-octreotide. J Nucl Med. 2005; 46(10):1696-700. View

Birn H, Christensen E . Renal albumin absorption in physiology and pathology. Kidney Int. 2006; 69(3):440-9. DOI: 10.1038/sj.ki.5000141. View

Wei L, Butcher C, Miao Y, Gallazzi F, Quinn T, Welch M . Synthesis and biologic evaluation of 64Cu-labeled rhenium-cyclized alpha-MSH peptide analog using a cross-bridged cyclam chelator. J Nucl Med. 2007; 48(1):64-72. View

10.

Miao Y, Benwell K, Quinn T . 99mTc- and 111In-labeled alpha-melanocyte-stimulating hormone peptides as imaging probes for primary and pulmonary metastatic melanoma detection. J Nucl Med. 2007; 48(1):73-80. View

11.

Miao Y, Gallazzi F, Guo H, Quinn T . 111In-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide analogues for melanoma imaging. Bioconjug Chem. 2008; 19(2):539-47. PMC: 3617549. DOI: 10.1021/bc700317w. View

12.

Cheng Z, Xiong Z, Subbarayan M, Chen X, Gambhir S . 64Cu-labeled alpha-melanocyte-stimulating hormone analog for microPET imaging of melanocortin 1 receptor expression. Bioconjug Chem. 2007; 18(3):765-72. PMC: 4143155. DOI: 10.1021/bc060306g. View

13.

Gotthardt M, van Eerd-Vismale J, Oyen W, de Jong M, Zhang H, Rolleman E . Indication for different mechanisms of kidney uptake of radiolabeled peptides. J Nucl Med. 2007; 48(4):596-601. DOI: 10.2967/jnumed.106.036020. View

14.

Garrison J, Rold T, Sieckman G, Naz F, Sublett S, Figueroa S . Evaluation of the pharmacokinetic effects of various linking group using the 111In-DOTA-X-BBN(7-14)NH2 structural paradigm in a prostate cancer model. Bioconjug Chem. 2008; 19(9):1803-12. PMC: 2647743. DOI: 10.1021/bc8001375. View

15.

Guo H, Shenoy N, Gershman B, Yang J, Sklar L, Miao Y . Metastatic melanoma imaging with an (111)In-labeled lactam bridge-cyclized alpha-melanocyte-stimulating hormone peptide. Nucl Med Biol. 2009; 36(3):267-76. PMC: 2685149. DOI: 10.1016/j.nucmedbio.2009.01.003. View

16.

Guo H, Yang J, Gallazzi F, Prossnitz E, Sklar L, Miao Y . Effect of DOTA position on melanoma targeting and pharmacokinetic properties of 111In-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide. Bioconjug Chem. 2009; 20(11):2162-8. PMC: 2786309. DOI: 10.1021/bc9003475. View

17.

Guo H, Yang J, Shenoy N, Miao Y . Gallium-67-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide for primary and metastatic melanoma imaging. Bioconjug Chem. 2009; 20(12):2356-63. PMC: 3009454. DOI: 10.1021/bc900428x. View

18.

Vegt E, Eek A, Oyen W, de Jong M, Gotthardt M, Boerman O . Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides. Eur J Nucl Med Mol Imaging. 2009; 37(2):226-34. PMC: 2816240. DOI: 10.1007/s00259-009-1239-1. View

19.

Guo H, Yang J, Gallazzi F, Miao Y . Reduction of the ring size of radiolabeled lactam bridge-cyclized alpha-MSH peptide, resulting in enhanced melanoma uptake. J Nucl Med. 2010; 51(3):418-26. PMC: 2998183. DOI: 10.2967/jnumed.109.071787. View

20.

Yang J, Guo H, Padilla R, Berwick M, Miao Y . Replacement of the Lys linker with an Arg linker resulting in improved melanoma uptake and reduced renal uptake of Tc-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptide. Bioorg Med Chem. 2010; 18(18):6695-700. PMC: 2947842. DOI: 10.1016/j.bmc.2010.07.061. View