99mTc-Duramycin imaging of high-dose ionizing irradiation-induced tissue injuries

Objectives Ionizing irradiation at sufficiently high dosages can cause injuries in susceptible tissues. The goal of this study was a proof-of-concept by imaging the temporal and spatial distribution of tissue induced by high-dose radiation exposure, using 99mTc-Duramycin as a phosphatidylethanolamine (PE)-binding radiopharmaceutical.

Methods Total body X-ray irradiation (15 Gy) was administered to a rat model. Planar whole-body 99mTc-Duramycin scans were conducted at 1, 2 and 3 days post irradiation using a clinical gamma camera. Additionally, micro-SPECT data were acquired with control and at 6 and 24 hours post irradiation. Imaging data were validated by gamma counting and histology.

Results Prominent focal uptake was detected in the thymus as early as 6 hours post-irradiation. This was followed by a gradual decline in 99mTc-Duramycin binding. Early (6-24 hour) radioactivity uptake in the gastrointestinal region was detected. Significant signal was seen in major bones in a slightly delayed fashion, at 24 hours, which persisted for at least 2 days. The kidneys, spleen and liver also had elevated signals. The imaging results were validated with ex vivo gamma counting results and histology.

Conclusions Our data demonstrated that the temporal and spatial dynamics of tissue injuries, as induced by high-dose ionizing irradiation, can be noninvasively imaged in a whole-body fashion. The results indicate that 99mTc-Duramycin is suitable for survey scans that can potentially be used in a broad range of imaging applications by detecting PE externalization as a surrogate marker for tissue injuries.

Research Support National Institute of Health (1R01HL102085)