TY - JOUR T1 - Favorable Biokinetic and Tumor-Targeting Properties of <sup>99m</sup>Tc-Labeled Glucosamino RGD and Effect of Paclitaxel Therapy JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 2000 LP - 2007 VL - 47 IS - 12 AU - Kyung-Ho Jung AU - Kyung-Han Lee AU - Jin-Young Paik AU - Bong-Ho Ko AU - Jun-Sang Bae AU - Byung Chul Lee AU - Hyun Ju Sung AU - Dong Hyun Kim AU - Yearn Seong Choe AU - Dae Yoon Chi Y1 - 2006/12/01 UR - http://jnm.snmjournals.org/content/47/12/2000.abstract N2 - Compared with the recent advancements in radiohalogenated Arg-Gly-Asp (RGD) peptides for αvβ3-targeted imaging, there has been limited success with 99mTc-labeled RGD compounds. In this article, we describe the favorable in vivo kinetics and tumor-imaging properties of a novel 99mTc-RGD compound that contains a glucosamine moiety. Methods: Glucosamino 99mTc-d-c(RGDfK) was prepared by incorporating 99mTc(CO)3 to the glucosamino peptide precursor in high radiochemical yield. Cell-binding characteristics were tested on human endothelial cells. Mice bearing RR1022 fibrosarcoma and Lewis lung carcinoma (LLC) tumors were used for in vivo biodistribution and blocking experiments and for imaging studies. Separate LLC-bearing mice underwent antiangiogenic therapy with 0, 20, or 40 mg of paclitaxel per kilogram of body weight every 2 d. Tumor volume was serially monitored, and tumor glucosamino 99mTc-d-c(RGDfK) uptake and Western blots of αv integrin expression were analyzed at day 14. Results: Glucosamino 99mTc-d-c(RGDfK) binding to endothelial cells was dose-dependently inhibited by excess RGD. Biodistribution in mice showed rapid blood clearance of glucosamino 99mTc-d-c(RGDfK), with substantially lower liver uptake and higher tumor uptake compared with 125I-c(RGD(I)yV). Tumor uptake was 1.03 ± 0.21 and 1.18 ± 0.26 %ID/g at 1 h and 0.85 ± 0.05 and 0.89 ± 0.28 %ID/g at 4 h for sarcomas and carcinomas, respectively. Excess RGD blocked uptake by 76.5% and 70.2% for the respective tumors. γ-Camera imaging allowed clear tumor visualization, with an increase of sarcoma-to-thigh count ratios from 5.5 ± 0.7 at 1 h to 10.1 ± 2.2 at 4 h and sustained carcinoma-to-thigh count ratios from 4 to 17 h. Pretreatment with excess cRGDyV significantly reduced tumor contrast on images. Paclitaxel therapy in LLC tumor–bearing mice significantly retarded tumor growth. This was accompanied by a corresponding reduction of tumor glucosamino 99mTc-d-c(RGDfK) uptake, which correlated significantly with tumor αv integrin expression levels. Conclusion: Glucosamino 99mTc-d-c(RGDfK) has favorable in vivo biokinetics and tumor-imaging properties and may be useful for noninvasive evaluation of tumor integrin expression and response to antiangiogenic therapeutics. Because of the wide accessibility of γ-cameras and high availability and excellent imaging characteristics of 99mTc, glucosamino 99mTc-d-c(RGDfK) may be an attractive alternative to radiohalogenated RGD peptides for angiogenesis-imaging research. ER -