A peptide targeted contrast agent specific to fibrin-fibronectin complexes for cancer molecular imaging with MRI.
A peptide targeted contrast agent, CLT1-(Gd-DTPA), was synthesized for molecular imaging of fibronectin-fibrin complexes in tumor tissue with magnetic resonance imaging (MRI). The T(1) and T(2) relaxivities of CLT1-(Gd-DTPA) were 4.22 and 4.45 mM(-1) s(-1) at 3 T, respectively. The targeted contrast agent specifically bound to tumor tissue and resulted in significant tumor contrast enhancement at a dose of 0.1 mmol Gd/kg for at least 60 min in mice bearing HT-29 human colon carcinoma xenografts as shown in dynamic MR images. In contrast, a control nontargeted contrast agent, Gd(DTPA-BMA), was cleared rapidly with little tumor enhancement 60 min postinjection. Tumor enhancement with CLT1-(Gd-DTPA) was significantly reduced after coinjection with a 3-fold excess of free CLT1 peptide. The preliminary study has shown that CLT1-(Gd-DTPA) can specifically bind to the fibrin-fibronectin complexes in tumor tissues, resulting in significant tumor enhancement. The targeted contrast agent has a potential for cancer molecular imaging with MRI.
Ye
Furong
F
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, and Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
Wu
Xueming
X
Jeong
Eun-Kee
EK
Jia
Zhanjun
Z
Yang
Tianxin
T
Parker
Denis
D
Lu
Zheng-Rong
ZR
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D019786:Gadolinium DTPA / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D003287:Contrast Media; D005353:Fibronectins; D010456:Peptides, Cyclic; D005337:Fibrin; D019786:Gadolinium DTPA