Dual optical and nuclear imaging in human melanoma xenografts using a single targeted imaging probe.
BACKGROUND
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 alphavbeta3. 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 alphavbeta3-positive M21 melanoma than in alphavbeta3-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 alphavbeta3-positive tumors, with optical images providing improved resolution and sensitive detection of the superficial lesions and gamma images providing sensitive detection of deeper structures.


CONCLUSIONS
The dual-labeled imaging probe 111In-DTPA-Lys(IRDye800)-c(KRGDf) was found to specifically bind to alphavbeta3 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.
Li
Chun
C
Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. cli@di.mdacc.tmc.edu
Wang
Wei
W
Wu
Qingping
Q
Ke
Shi
S
Houston
Jessica
J
Sevick-Muraca
Eva
E
Dong
Liang
L
Chow
Diana
D
Charnsangavej
Chusilp
C
Gelovani
Juri G
JG
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes; D007211:Indoles; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D015336:Molecular Probe Techniques; D009842:Oligopeptides / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000737:chemistry*; D049268:Positron-Emission Tomography; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
D005456:Fluorescent Dyes; C427728:IRDye800; D007205:Indium Radioisotopes; D007211:Indoles; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D004369:Pentetic Acid