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

Li, Chun; Wang, Wei; Wu, Qingping; Ke, Shi; Houston, Jessica; Sevick-Muraca, Eva; Dong, Liang; Chow, Diana; Charnsangavej, Chusilp; Gelovani, Juri G.

doi:10.1016/j.nucmedbio.2006.01.001

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 349-358, April 2006

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

Chun Li
- Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
- Corresponding author. Tel.: +1 713 792 5182; fax: +1 713 794 5456.
Wei Wang
- Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
Qingping Wu
- Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
Shi Ke
- Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
Jessica Houston
- Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA
Eva Sevick-Muraca
- Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA
Liang Dong
- Department of Pharmaceutical Sciences, Texas Southern University, Houston, TX 77030, USA
Diana Chow
- Department of Pharmacology and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77030, USA
Chusilp Charnsangavej
- Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
Juri G. Gelovani
- Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA

Received 10 December 2005; received in revised form 2 January 2006; accepted 3 January 2006.

Abstract

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

¹¹¹In-DTPA-Lys(IRDye800)-c(KRGDf) composed of both the ¹¹¹In 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 αvβ3. 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 ¹¹¹In-DTPA-Lys(IRDye800)-c(KRGDf) and ¹¹¹In-DTPA-Lys-c(KRGDf) had significantly higher uptakes in αvβ3-positive M21 melanoma than in αvβ3-negative M21-L melanoma at 4–48 h after their injection. Side-by-side comparison of images obtained using ¹¹¹In-DTPA-Lys(IRDye800)-c(KRGDf) revealed that in living mice, both optical imaging and gamma scintigraphy enabled noninvasive detection of the bound probe to αvβ3-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 ¹¹¹In-DTPA-Lys(IRDye800)-c(KRGDf) was found to specifically bind to αvβ3 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.

Keywords: Optical imaging, Nuclear imaging, Integrins, Dual modality, Melanoma, Peptide