Characterization, biodistribution and small-animal SPECT of I-125-labeled c-Met binding peptide in mice bearing c-Met receptor tyrosine kinase-positive tumor xenografts.
c-Met is a receptor tyrosine kinase involved in tumor cell growth, invasion, metastases and angiogenesis. Overexpression of c-Met is frequently observed in several tumor types. Here, we report the in vitro cell-binding properties and biodistribution and SPECT/CT imaging in glioma (U87MG) xenograft-bearing mice of (125)I-labeled c-Met-binding peptides (cMBPs) including analogs conjugated to amino acid and aliphatic carbon linkers. In vitro assays showed that the peptide without any linker and those with GGG and 8-aminooctanoic acid linkers had low cellular internalization and that IC(50) values of peptides were 1.5 microM, 65 nM and 85.3 nM, respectively. Biodistribution studies showed the GGG-containing peptide had higher tumor uptake and a higher tumor-to-blood activity concentration ratio than other receptor-binding ligands. SPECT/CT studies with a dedicated small-animal imaging system were performed in U87MG-bearing athymic mice. Although U87MG tumor xenografts could be visualized by SPECT/micro-CT using the various (125)I labeled cMBPs, image contrast and overall quality were unremarkable.
Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju-si, Jeonbuk 561-712, Republic of Korea.
Eun-Mi
EM
Kim
Eun-Hye
EH
Park
Su-Jin
SJ
Cheong
Chang-Moon
CM
Lee
Dong Wook
DW
Kim
Hwan-Jeong
HJ
Jeong
Seok Tae
ST
Lim
Myung-Hee
MH
Sohn
Kisu
K
Kim
Junho
J
Chung
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D015153:Blotting, Western; D002210:Caprylates / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000601:surgery; D005998:Glycine / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous
D002210:Caprylates; D007457:Iodine Radioisotopes; D010455:Peptides; C046323:omega-aminocaprylic acid; D019859:Proto-Oncogene Proteins c-met; D005998:Glycine