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Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates: potential peptide radiotherapeutics for somatostatin receptor-positive cancers.

Publication ,  Journal Article
Vaidyanathan, G; Boskovitz, A; Shankar, S; Zalutsky, MR
Published in: Peptides
December 2004

Derivatives of the somatostatin analogues octreotide and octreotate labeled with radioiosotopes are used in the diagnosis and therapy of somatostatin receptor (SSTR)-positive tumors. A method has been devised to synthesize {N-(4-guanidinomethyl-3-iodobenzoyl)-Phe1-octreotate (GMIBO). Receptor binding assay and scatchard analysis yielded a Kd of 4.83 +/- 0.19 nM for this peptide. Derivatives of this peptide labeled with radioiodine ([*I]GMIBO) and the alpha-particle-emitting radiohalogen 211At N-(3-[211At]astato-4-guanidinomethylbenzoyl)-Phe1-octreotate; [211At]AGMBO} were prepared in a single step from a tin precursor in radiochemical yields of 30-35% and 15-20%, respectively. Paired-label internalization assays performed with the SSTR-positive D341 Med human medulloblastoma cell line demonstrated that [125I]GMIBO and [211At]AGMBO were specifically internalized 20-40% more than Nalpha-(1-deoxy-D-fructosyl)-[131I]I-Tyr3-octreotate ([131I]I-Glu-TOCA), the radioiodinated octreotide derivative previously shown to exhibit maximum internalization in this cell line. Uptake of [131I]GMIBO in D341 Med subcutaneous xenografts in a murine model (8.34 +/- 1.82 versus 8.10 +/- 2.23% ID/g at 1h) and SSTR-expressing normal tissues was comparable to that of [125I]I-Glu-TOCA and was shown to be specific. However, the uptake of [131I]GMIBO also was substantially higher in liver (16.9 +/- 3.15 versus 1.39 +/- 0.45% ID/g at 1 h) and in kidneys (44.33 +/- 6.47 versus 3.44 +/- 0.68% ID/g at 1h) compared to that of [125I]I-Glu-TOCA. These data suggest that these novel peptide conjugates retain their specificity for SSTR both in vitro and in vivo; however, because of their higher accumulation in normal tissues they would be best applied in settings amenable to loco-regional administration such as medulloblastoma neoplastic meningitis.

Duke Scholars

Published In

Peptides

DOI

ISSN

0196-9781

Publication Date

December 2004

Volume

25

Issue

12

Start / End Page

2087 / 2097

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Distribution
  • Receptors, Somatostatin
  • Rats
  • Peptides, Cyclic
  • Pancreatic Neoplasms
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • Medulloblastoma
 

Citation

APA
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ICMJE
MLA
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Vaidyanathan, G., Boskovitz, A., Shankar, S., & Zalutsky, M. R. (2004). Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates: potential peptide radiotherapeutics for somatostatin receptor-positive cancers. Peptides, 25(12), 2087–2097. https://doi.org/10.1016/j.peptides.2004.08.018
Vaidyanathan, Ganesan, Abraham Boskovitz, Sriram Shankar, and Michael R. Zalutsky. “Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates: potential peptide radiotherapeutics for somatostatin receptor-positive cancers.Peptides 25, no. 12 (December 2004): 2087–97. https://doi.org/10.1016/j.peptides.2004.08.018.
Vaidyanathan, Ganesan, et al. “Radioiodine and 211At-labeled guanidinomethyl halobenzoyl octreotate conjugates: potential peptide radiotherapeutics for somatostatin receptor-positive cancers.Peptides, vol. 25, no. 12, Dec. 2004, pp. 2087–97. Pubmed, doi:10.1016/j.peptides.2004.08.018.
Journal cover image

Published In

Peptides

DOI

ISSN

0196-9781

Publication Date

December 2004

Volume

25

Issue

12

Start / End Page

2087 / 2097

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Distribution
  • Receptors, Somatostatin
  • Rats
  • Peptides, Cyclic
  • Pancreatic Neoplasms
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • Medulloblastoma