RT Journal Article SR Electronic T1 Detection of Apoptotic Tumor Response In Vivo After a Single Dose of Chemotherapy with 99mTc-Annexin V JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 92 OP 97 VO 44 IS 1 A1 Takafumi Mochizuki A1 Yuji Kuge A1 Songji Zhao A1 Eriko Tsukamoto A1 Masuo Hosokawa A1 H. William Strauss A1 Francis G. Blankenberg A1 Jonathan F. Tait A1 Nagara Tamaki YR 2003 UL http://jnm.snmjournals.org/content/44/1/92.abstract AB Annexin V, a human protein with a high affinity for phosphatidylserine, has been labeled with 99mTc to detect apoptosis in vivo. To determine the effectiveness of imaging with this agent as a reflection of the degree of apoptosis after the first dose of chemotherapy, we studied rats with an engrafted hepatoma. Methods: Annexin V was labeled with 99mTc (specific activity, 3.0 MBq/μg protein). Eleven days after being inoculated with allogenic hepatoma cells (KDH-8) in the left calf muscle, the rats were randomized to receive a single dose of cyclophosphamide (150 mg/kg intraperitoneally) or to serve as controls. 99mTc-annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h after injection of 99mTc-annexin V. Tumor uptake of 14C-iodoanitpyrine was determined as a marker of tumor blood flow. Terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL) of tissue harvested at necropsy was performed to detect apoptosis in the tumor. Results: Cyclophosphamide treatment significantly increased the tumor uptake (percentage activity of injected dose per gram of tissue after normalization to the animal’s weight [%ID/g/kg]) of 99mTc-annexin V (0.070 ± 0.007 %ID/g/kg for treated rats and 0.046 ± 0.009 %ID/g/kg for controls, P < 0.001). 14C-iodoantipyrine uptake was similar in the treated and untreated groups. The number of TUNEL-positive cells in the tumor was significantly larger in the treated rats (297.70 ± 50.34 cells/mm2) than in the control rats (168.45 ± 23.60 cells/mm2, P < 0.001). Tumor uptake of 99mTc-annexin V correlated with the number of TUNEL-positive cells in the tumor (r = 0.712; P < 0.001). Conclusion: Tumor uptake of 99mTc-annexin V was significantly increased by a single dose of cyclophosphamide treatment, and the increase was concordant with the number of TUNEL-positive cells in the tumor. The current results are suggestive of the utility of 99mTc-annexin V as a noninvasive means to assess tumor response, although further testing, including clinical evaluation, is required.