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U.S. Department of Energy
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Targeted Therapy for Melanoma

Technical Report ·
DOI:https://doi.org/10.2172/1334319· OSTI ID:1334319
 [1];  [2]
  1. Alphamed, Jackson, TN (United States); University of Missouri
  2. Alphamed, Jackson, TN (United States)

The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

Research Organization:
Alphamed, Jackson, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Contributing Organization:
Univ. of Missouri, Columbia, MO (United States)
DOE Contract Number:
SC0005738
OSTI ID:
1334319
Report Number(s):
DOE-Alphamed--sc0005738
Country of Publication:
United States
Language:
English

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