Evaluation of 111In-labeled Anginex as Potential SPECT Tracer for Imaging of Tumor Angiogenesis.
Angiogenesis is a prerequisite for solid tumors to grow and metastasize, providing oxygen and nutrients to the tumor site. The protein galectin-1 has been identified to be overexpressed on tumor vasculature and represents an interesting target for anti-angiogenic therapy, as well as in molecular imaging. Therefore, the galectin-1-binding peptide Anginex was modified for radiolabeling using (111)In. In vitro, (111)In-Ax showed significantly more binding to galectin-1-positive EC-RF24 and MDA-MB-231-LITG cells than to galectin-1-negative LS174T cells and association with EC-RF24 cells was reduced in the presence of excess native Anginex. However, ex vivo biodistribution profiles showed little tumor uptake of (111)In-Ax and extensive accumulation in non-target organs. Although this study shows the ease of modification of the therapeutic peptide Anginex and favorable characteristics in vitro, in vivo assessment of the tracer revealed negligible tumor targeting. Hence, the strategy we employed lends little support for successful non-invasive imaging of tumor angiogenesis using this peptide.
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Tiemen R
TR
Van Mourik
Oncology Solutions, Philips Research, Eindhoven, the Netherlands.
Tilman
T
Läppchen
Oncology Solutions, Philips Research, Eindhoven, the Netherlands Tagworks Pharmaceuticals, Eindhoven, the Netherlands.
Raffaella
R
Rossin
Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
Judy R
JR
Van Beijnum
PepTx, Inc., Excelsior, Minnesota, MN, U.S.A.
John R
JR
Macdonald
Department of Biochemistry, University of Minnesota, Minneapolis, MN, U.S.A.
Kevin H
KH
Mayo
Angiogenesis Laboratory, Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
Arjan W
AW
Griffioen
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Klaas
K
Nicolay
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands Oncology Solutions, Philips Research, Eindhoven, the Netherlands h.gruell@tue.nl.
Holger
H
Grüll
D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D037483:Galectin 1 / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D010455:Peptides / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D037483:Galectin 1; D007205:Indium Radioisotopes; D010455:Peptides; D011849:Radioactive Tracers; C558923:anginex peptide
Anginex; cancer; galectin-1; indium-111; tumor angiogenesis