Monitoring early tumor response to radiotherapy using ^99mTc-duramycin

Objectives Apoptosis induces phosphatidylethanolamine (PE) externalization. Duramycin is a peptide that recognizes cell death by binding to externalized PE with high affinity and specificity. Moreover, ^99mTc-duramycin uptake was demonstrated to be dependent on PE exposure. The aim of this work was to evaluate the usefulness of ^99mTc-duramycin for imaging of radiotherapy induced cell death.

Methods A subcutaneous mouse model of colorectal cancer was created using Colo205 cells. Tumor growth was monitored using caliper measurements, before and after single tumor irradiation (4.5 Gy), repeated tumor irradiation (2 times 4.5 Gy; 24 h interval), repeated tumor irradiation (2 times 4.5 Gy; 24 h interval) combined with 80 mg/kg irinotecan or in controls (n=5-6/group). ^99mTc-Duramycin (0.94 ± 0.09 mCi) was intravenously injected 24 h after treatment. Static SPECT-CT images were acquired 4 h post-radiotracer injection. Afterwards mice were sacrificed for biodistribution, autoradiography and immunohistochemistry (IHC) of tumors (TUNEL and cleaved caspase-3 staining).

Results All treatments significantly inhibited tumor growth when compared to controls. SPECT-CT imaging did not show significant differences in tumor ^99mTc-duramycin uptake after treatment. However, γ-counting of the tumors showed higher ^99mTc-duramycin uptake in treated tumors. Regional tracer uptake was visible on autoradiography. Correlation between ^99mTc-duramycin uptake and apoptosis is currently being evaluated by IHC.

Conclusions In conclusion, ^99mTc-duramycin specifically accumulates in tumors responding to therapy. It might therefore be a promising tracer for early evaluation of tumor response to therapy.

Research Support University of Antwerp (GOA BOF grant)