Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with 99mTc-annexin V

J Nucl Med. 2003 Jan;44(1):92-7.

Abstract

Annexin V, a human protein with a high affinity for phosphatidylserine, has been labeled with (99m)Tc 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 (99m)Tc (specific activity, 3.0 MBq/ micro g 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. (99m)Tc-annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h after injection of (99m)Tc-annexin V. Tumor uptake of (14)C-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 (99m)Tc-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). (14)C-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/mm(2)) than in the control rats (168.45 +/- 23.60 cells/mm(2), P < 0.001). Tumor uptake of (99m)Tc-annexin V correlated with the number of TUNEL-positive cells in the tumor (r = 0.712; P < 0.001).

Conclusion: Tumor uptake of (99m)Tc-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 (99m)Tc-annexin V as a noninvasive means to assess tumor response, although further testing, including clinical evaluation, is required.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A5 / pharmacokinetics*
  • Apoptosis / drug effects*
  • Cyclophosphamide / therapeutic use*
  • Dose-Response Relationship, Drug
  • In Situ Nick-End Labeling
  • Liver Neoplasms, Experimental / diagnostic imaging
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Neoplasm Transplantation
  • Organotechnetium Compounds / pharmacokinetics*
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Reference Values
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • Treatment Outcome
  • Tumor Cells, Cultured

Substances

  • Annexin A5
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium Tc 99m annexin V
  • Cyclophosphamide