Effect of molecular charges on renal uptake of 111In-DTPA-conjugated peptides

Hiromichi Akizawa, Yasushi Arano, Masaki Mifune, Akimasa Iwado, Yutaka Saito, Takahiro Mukai, Tomoya Uehara, Masahiro Ono, Yasushi Fujioka, Kazuma Ogawa, Yoshiaki Kiso, Hideo Saji

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


The effect of molecular charges on renal accumulation of 111In-DTPA-labeled low molecular weight (LMW) peptides was investigated using 111In-DTPA-octreotide derivatives as models to design radiolabeled peptides that are taken up less by renal cells. The N-terminal D-phenylalanine (Phe) of 111In-DTPA-D-Phe1-octreotide was replaced with L-aspartic acid (Asp), L-lysine (Lys), L-methionine (Met) or L-Phe. Cellulose acetate electrophoresis indicated that both 111In-DTPA-L-Phe1-octreotide and 111In-DTPA-L-Met1-octreotide showed similar net charges, whereas 111In-DTPA-L-αLys1-octreotide and 111In-DTPA-L-Asp1-octreotide had more positive and negative charges, respectively, at pH values similar to those in blood and glomerular filtrate. When injected into mice, significant differences were observed in the renal radioactivity levels. 111In-DTPA-L-αLys1-octreotide showed the highest radioactivity levels from 10 min to 6 h postinjection, whereas the lowest radioactivity levels were observed with 111In-DTPA-L-Asp1-octreotide at all the postinjection intervals. These findings indicated that the replacement of only one amino acid in 111In-DTPA-D-Phe1-octreotide significantly altered net molecular charges of the resulting peptides and that the net charges of the 111In-DTPA-octreotide derivatives significantly affected their renal uptake. Thus, an increase of negative charges in peptide molecules may constitute a strategy for designing 111In-DTPA-conjugated LMW peptides with low renal radioactivity levels.

Original languageEnglish
Pages (from-to)761-768
Number of pages8
JournalNuclear Medicine and Biology
Issue number7
Publication statusPublished - 2001
Externally publishedYes


  • In-DTPA-peptide
  • Molecular charge
  • Octreotide
  • Re-absorption
  • Renal radioactivity localization

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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