Octreotide Functionalized Nano-Contrast Agent for Targeted Magnetic Resonance Imaging

Reversible addition-fragmentation chain transfer (RAFT) polymerization has been employed to synthesize branched block copolymer nanoparticles possessing 1,4,7,10-tetraazacyclododecane-N,N,'N,″N,‴-tetraacetic acid (DO3A) macrocycles within their cores and octreotide (somatostatin mimic) cyclic peptides at their periphery. These polymeric nanoparticles have been chelated with Gd³⁺ and applied as magnetic resonance imaging (MRI) nanocontrast agents. This nanoparticle system has an r₁ relaxivity of 8.3 mM^-1 s^-1, which is 3 times the r₁ of commercial gadolinium-based contrast agents (GBCAs). The in vitro targeted binding efficiency of these nanoparticles shows 5 times greater affinity to somatostatin receptor type 2 (SSTR2) with K_i = 77 pM (compared to somatostatin with K_i = 0.385 nM). We have also evaluated the tumor targeting molecular imaging ability of these branched copolymer nanoparticle in vivo using nude/NCr mice bearing AR42J rat pancreatic tumor (SSTR2 positive) and A549 human lung carcinoma tumor (SSTR2 negative) xenografts.