Preclinical evaluation of the breast cancer cell-binding peptide, p160.
OBJECTIVE
Selective delivery of drugs into the target tissue is expected to result in high drug concentrations in the tissue of interest and therefore enhanced drug efficacy. To develop a peptide-based radiopharmaceutical, we investigated the properties of a peptide with affinity for human breast cancer, which has been selected through phage display.


METHODS
The bioactivity of the p160 peptide (VPWMEPAYQRFL) was evaluated in vitro and in vivo. The specific binding to human breast cancer MDA-MB-435 cells was confirmed in competition experiments. Internalization of the peptide was investigated with confocal microscopy. Furthermore, the biodistribution of (131)I-labeled p160 was studied in tumor-bearing mice. In vivo stability was evaluated at different periods after tracer administration using high-performance liquid chromatography analysis.


RESULTS
The binding of (125)I-labeled p160 was inhibited up to 95% by the unlabeled peptide with an IC(50) value of 0.6 micromol/L. In addition, 40% of the total bound activity was found to be internalized into the human breast cancer cells. Although a rapid degradation was seen, biodistribution studies in nude mice showed a higher uptake in tumor than in most of the organs. Perfusion of the animals caused a reduction of the radioligand accumulation in the healthy tissues, whereas the tumor uptake remained constant. A comparison of [(131)I]p160 with a (131)I-labeled Arg-Gly-Asp peptide revealed a higher tumor-to-organ ratio for [(131)I]p160.


CONCLUSIONS
p160 has properties that make it an attractive carrier for tumor imaging and the intracellular delivery of isotopes or chemotherapeutic drugs.
Askoxylakis
Vasileios
V
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, University of Heidelberg, Germany.
Zitzmann
Sabine
S
Mier
Walter
W
Graham
Keith
K
Krämer
Susanne
S
von Wegner
Frederic
F
Fink
Rainer H A
RH
Schwab
Manfred
M
Eisenhut
Michael
M
Haberkorn
Uwe
U
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000378:metabolism / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000378:metabolism* / Q000493:pharmacokinetics; D011869:Radioligand Assay; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D009842:Oligopeptides; D015282:Octreotide