Dual optical and nuclear imaging in human melanoma xenografts using a single targeted imaging probe

Introduction: Dual-labeled imaging agents that allow both nuclear and optical imaging after a single injection would be advantageous in certain applications. In this study, we synthesized and characterized a dual-labeled RGD (Arg-Gly-Asp) peptide and compared nuclear and optical images obtained with this agent. Methods: In-111-DTPA-Lys(IRDye800)-c(KRGDt) composed of both the In-111 chelator diethylenetriaminepentaacetic acid (DTPA) and the near-infrared (NIR) fluorescent dye IRDye800 (excitation/emission, 765/792 nm) was synthesized. The probe was characterized with regard to in vitro biological activity and in vivo pharmacokinetics and the ability to target integrin alpha v beta 3. Tumors of mice injected with the dual-labeled probe were imaged both by gamma scintigraphy and NIR fluorescence optical camera. Results: DTPA-Lys(IRDye800)-c(KRGDf), DTPA-Lys-c(KRGDf) and c(KRGDf) inhibited the adhesion of melanoma M21 cells to vitronectin-coated surface with the similar biological activity. Both In-111-DTPA-Lys(IRDye800)-c(KRGDf) and In-111-DTPA-Lys-c(KRGDf) had significantly higher uptakes in alpha v beta 3-positive M21 melanoma than in alpha v beta 3-negative M21-L melanoma at 4-48 11 after their injection. Side-by-side comparison of images obtained using In-111-DTPA-Lys(IRDyc800)-c(KRGDf) revealed that in living mice, both optical imaging and gamma scintigraphy enabled noninvasive detection of the bound probe to alpha v beta 3-positive tumors, with optical images providing improved resolution and sensitive detection of the superficial lesions and gamma images providing sensitive detection of deeper structures. Conclusion: The dual-labeled imaging probe In-111-DTPA-Lys(IRDye800)-c(KRGDf) was found to specifically bind to alpha v beta 3 in melanoma tumor cells. Employing both nuclear and optical imaging with a single imaging probe may facilitate translation of NIR fluorescence optical imaging into clinical applications. (c) 2006 Elsevier Inc. All rights reserved.