@article {Takei2083, author = {Toshiki Takei and Yuji Kuge and Songji Zhao and Masayuki Sato and H. William Strauss and Francis G. Blankenberg and Jonathan F. Tait and Nagara Tamaki}, title = {Time Course of Apoptotic Tumor Response After a Single Dose of Chemotherapy: Comparison with 99mTc-Annexin V Uptake and Histologic Findings in an Experimental Model }, volume = {45}, number = {12}, pages = {2083--2087}, year = {2004}, publisher = {Society of Nuclear Medicine}, abstract = {In tumors the process of apoptosis occurs over an interval of time after chemotherapy. To determine the best timing for detecting apoptosis in vivo with 99mTc-annexin V after chemotherapy, we examined the changes in 99mTc-annexin V accumulation over time in comparison with those of caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) expression level after cyclophosphamide treatment in an experimental model. Methods: Hydrazinonicotinamide (HYNIC)-annexin V was labeled with 99mTc (99mTc-annexin V). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after the inoculation, the rats were randomly divided into the group receiving a single dose of cyclophosphamide (150 mg/kg intraperitoneally) and the control group. 99mTc-Annexin V (18.5 MBq [0.5 mCi] per rat) was injected intravenously in the rats 4, 12, and 20 h after the treatment and also to the control rats (n = 5 in each group). Radioactivity in tissues was determined 6 h after 99mTc-annexin V injection. Immunostaining of caspase-3 and TUNEL were performed to detect apoptosis, and the rates of positively stained cells were calculated. Results: 99mTc-Annexin V accumulation in tumors significantly increased at 20 h (0.077 {\textpm} 0.007 [\%ID/g] {\texttimes} kg, where \%ID/g = percentage injected dose per gram) but not at 4 or 12 h (0.048 {\textpm} 0.008 and 0.052 {\textpm} 0.014 [\%ID/g] {\texttimes} kg, respectively) after cyclophosphamide treatment. 99mTc-Annexin V accumulation in tumors and the rate of apoptotic cells determined by caspase-3 immunostaining and TUNEL were significantly higher in treated rats 20 h after cyclophosphamide treatment as compared with control rats. Conclusion: The effective detection of apoptotic tumor response with 99mTc-annexin V required 20 h after cyclophosphamide treatment in an experimental model. The present results provide an important basis for determining the best timing of annexin V imaging after the start of chemotherapy in a clinical setting.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/45/12/2083}, eprint = {https://jnm.snmjournals.org/content/45/12/2083.full.pdf}, journal = {Journal of Nuclear Medicine} }