Research Articles: Therapeutics, Targets, and Development

In vivo optical imaging of human lymphoma xenograft using a library-derived peptidomimetic against 41 integrin

¹ Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis Cancer Center, Sacramento, California

^* To whom correspondence should be addressed. E-mail: Kit.Lam{at}ucdmc.ucdavis.edu.

	Abstract

Increasing literature suggests that cell adhesion molecule 41 integrin plays a pivotal role in autoimmune diseases and cancer development. Noninvasive visualization of 41 integrin in vivo will facilitate the understanding of its involvement in disease progression and development of targeted therapies. Due to the lack of high-affinity targeting ligands, molecular imaging of 41 integrin is much less explored than that of v3 and v5 integrins. We have recently reported using the one bead–one compound combinatorial library method to identify a peptidomimetic, LLP2A, that preferentially binds to activated 41 integrin. Here, we described the use of LLP2A-Cy5.5 conjugate as an in vivo optical imaging probe in a human lymphoma xenograft model. This univalent LLP2A-Cy5.5 conjugate retained the binding activity and specificity to 41 integrin as shown by cell binding assays using 41-positive Molt-4 T-leukemia cells. The subcutaneous Molt-4 tumor was clearly visualized from 1 to 24 h after tail vein injection of the conjugate. Direct imaging and confocal microscopic examination of excised tumors and organs confirmed the accumulation of LLP2A in tumors and revealed very little or no uptake in normal organs except for lymph nodes. Kidney uptake was high when the whole organ was scanned but it was negative when examined microscopically, suggesting that LLP2A bound to the renal tubules loosely. Tumor uptake of LLP2A-Cy5.5 conjugate was blocked by excess unlabeled LLP2A. This study showed that the combinatorial chemical library-derived peptidomimetic LLP2A can be easily developed into an optical imaging probe for noninvasively monitoring of activated 41 integrin in vivo. [Mol Cancer Ther 2008;7(2):OF1–6]

Key Words: 41 integrin, NIR fluorescence imaging, tumor targeting, optical imaging, combinatorial chemistry library, one bead–one compound combinatorial chemistry