Imaging Prostate Cancer Microenvironment by Collagen Hybridization
Technical Report,30 Sep 2015,29 Sep 2016
University of Utah Salt Lake City United States
Pagination or Media Count:
In order to find out why our CMP based imaging agent produced weak signals in vivo, we performed to serum stability test. Here, we report the serum stability of a series of monomeric CMP derivatives and establish how peptide length, amino acid composition, terminal modification, and linker chemistry influence their availability in serum. We show that monomeric CMPs comprised of the collagen-like Gly-Pro-Hyp motif are resistant to common serum proteinases and that their stability can be further increased by simple N-terminal labeling which negates CMPs susceptibility to proline-specific exopeptidases. When fluorescent dyes are conjugated to CMP via maleimide-thiol reaction, the dye can transfer from CMP onto serum proteins e.g. albumin resulting in an unexpected drop in signal during serum stability assays and off-target accumulation during in vivo tests. This work is the crucial first step toward understanding the pharmacokinetic behavior of CMPs which can facilitate thedevelopment of CHP-based diagnostics.
- Medicine and Medical Research