RT Journal Article SR Electronic T1 Imaging Taxane-Induced Tumor Apoptosis Using PEGylated, 111In-Labeled Annexin V JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 108 OP 115 VO 45 IS 1 A1 Shi Ke A1 Xiaoxia Wen A1 Qing-Ping Wu A1 Sidney Wallace A1 Chusilp Charnsangavej A1 Anne M. Stachowiak A1 Clifton L. Stephens A1 James L. Abbruzzese A1 Donald A. Podoloff A1 Chun Li YR 2004 UL http://jnm.snmjournals.org/content/45/1/108.abstract AB 99mTc-Labeled annexin V has been used for the imaging of tumor apoptosis induced by chemotherapy. However, owing to the short half-life of annexin V, multiple injections of the radiotracer are necessary to capture the peak apoptotic activity. In this study, we evaluated the imaging properties of an 111In-labeled, long-circulating annexin V. Methods: Both polyethylene glycol (PEG) and the metal chelator diethylenetriaminepentaacetic acid (DTPA) were simultaneously introduced to annexin V or ovalbumin through the use of a heterofunctional PEG precursor. Imaging studies were performed in mice bearing subcutaneously inoculated human mammary MDA-MB-468 tumors. The mice were treated with poly(l-glutamic acid)-paclitaxel, monoclonal antibody C225, or a combination of poly(l-glutamic acid)-paclitaxel and C225, followed by intravenous injection of 111In-DTPA-PEG-annexin V. Images were acquired 48 h after the injection of the radiotracer. Autoradiography and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) staining were performed on adjacent tumor slices for the localization of apoptotic cells. The imaging properties of unPEGylated annexin V and PEGylated ovalbumin were also determined to permit assessment of the specificity of 111In-DTPA-PEG-annexin V. Results: Tumor apoptotic index increased from 1.67% ± 0.31% at baseline to 7.60% ± 0.72% and 11.07% ± 1.81%, respectively, 4 d after treatment with poly(l-glutamic acid)-paclitaxel or combined poly(l-glutamic acid)-paclitaxel and C225. Tumor uptake (percentage of injected dose per gram of tumor [%ID/g]) of PEGylated 111In-DTPA-PEG-annexin 4 d after treatment was significantly higher in tumors treated with poly(l-glutamic acid)-paclitaxel (10.76 ± 1.38 %ID/g; P = 0.001) and with combined poly(l-glutamic acid)-paclitaxel and C225 (9.84 ± 2.51 %ID/g; P = 0.029) than in nontreated tumors (6.14 ± 0.67 %ID/g), resulting in enhanced visualization of treated tumors. 111In-DTPA-PEG-annexin V distributed into the central zone of tumors, whereas 111In-DTPA-annexin V was largely confined to the tumor periphery. Furthermore, uptake of 111In-DTPA-PEG-annexin V by tumors correlated with apoptotic index (r = 0.87, P = 0.02). Increase in tumor uptake of the nonspecific PEGylated protein 111In-DTPA-PEG-ovalbumin was also observed after poly(l-glutamic acid)-paclitaxel treatment (55.6%), although this increase was less than that observed for 111In-DTPA-PEG-annexin V (96.7%). Conclusion: Increased uptake of and improved visualization with 111In-DTPA-PEG-annexin V in solid tumors after chemotherapy are mediated through both specific binding to apoptotic cells and nonspecific retention of macromolecular contrast agents in the tumors. 111In-Labeled, PEGylated annexin V may be used to assess tumor response to chemotherapy.