TY - JOUR
T1 - Effect of molecular charges on renal uptake of 111In-DTPA-conjugated peptides
AU - Akizawa, Hiromichi
AU - Arano, Yasushi
AU - Mifune, Masaki
AU - Iwado, Akimasa
AU - Saito, Yutaka
AU - Mukai, Takahiro
AU - Uehara, Tomoya
AU - Ono, Masahiro
AU - Fujioka, Yasushi
AU - Ogawa, Kazuma
AU - Kiso, Yoshiaki
AU - Saji, Hideo
N1 - Funding Information:
The authors thank Mr. Shinsaku Nakayama and Mr. Naozumi Ohnishi for their technical support. This work was supported in part by a Grant from Association for Nuclear Technology in Medicine, Japan.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - In-DTPA-peptide
KW - Molecular charge
KW - Octreotide
KW - Re-absorption
KW - Renal radioactivity localization
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U2 - 10.1016/S0969-8051(01)00241-4
DO - 10.1016/S0969-8051(01)00241-4
M3 - Article
C2 - 11578896
AN - SCOPUS:0034802793
VL - 28
SP - 761
EP - 768
JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
SN - 0969-8051
IS - 7
ER -