In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma

Beau Ballard, Zewei Jiang, Clifford E. Soll, Ekaterina Revskaya, Cathy S. Cutler, Ekaterina Dadachova, Lynn C. Francesconi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Melanoma is a malignancy with increasing incidence. Although primary tumors that are localized to the skin can be successfully treated by surgical removal, there is no satisfactory treatment for metastatic melanoma, a condition that has currently an estimated 5-year survival of just 6%. During the last decade, β-or α-emitter-radiolabeled peptides that bind to different receptors on a variety of tumors have been investigated as potential therapeutic agents in both the preclinical and clinical settings with encouraging results. A recent study demonstrated that 188-Rhenium ( 188Re)-labeled, via HYNIC ligand, fungal melanin-binding decapeptide 4B4 was effective against experimental MNT1 human melanoma and was safe to normal melanized tissues. The availability of radiolanthanides with diverse nuclear emission schemes and half-lives provides an opportunity to expand the repertoire of peptides for radionuclide therapy of melanoma. The melanin-binding decapeptide 4B4 was radiolabeled with 177Lu, 166Ho, and 153Sm via a DO3A chelate. The stability studies of Ln*-DO3A-4B4 in phosphate-buffered saline, serum, and a hydroxyapatite assay demonstrated that 177Lu-labeled peptide was more stable than 166Ho-and 153Sm-labeled peptides, most likely because of the smallest ionic radius of the former allowing for better complexation with DO3A. Binding of Ln*-DO3A-4B4 to the lysed highly melanized MNT1 melanoma cells demonstrated the specificity of peptides binding to melanin. In vivo biodistribution data for 177Lu-DO3A-4B4 given by intraperitoneal administration to lightly pigmented human metastatic A2058 melanoma-bearing mice demonstrated very high uptake in the kidneys and low tumor uptake. Intravenous administration did not improve the tumor uptake. The plausible explanation of low tumor uptake of 177Lu-DO3A-4B4 could be its decreased ability to bind to melanin during in vitro binding studies in comparison with 188Re-HYNIC-4B4, exacerbated by the very fast clearance from the blood and the kidneys "sink" effect.

Original languageEnglish (US)
Pages (from-to)547-556
Number of pages10
JournalCancer Biotherapy and Radiopharmaceuticals
Issue number5
StatePublished - Oct 1 2011


  • cancer
  • melanoma
  • radioimmunotherapy
  • radiopharmaceuticals
  • targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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