Imaging of therapy-induced apoptosis using (99m)Tc-HYNIC-annexin V in thymoma tumor-bearing mice.

The primary focus of this study was to assess the potential of (99m)Tc-HYNIC-Annexin V for in vivo imaging of apoptosis after systemic chemotherapy and "more localized" radiotherapy in nude mice bearing thymoma tumors and correlating it with TUNEL staining. (99m)Tc-HYNIC-Annexin V was administered intravenously to tumor-bearing mice (n = 25) before and after therapy. Mice were then imaged at 4 hours postinjection, and the animals were subsequently sacrificed. Tumor uptake increased significantly in response to treatment [chemotherapy (n = 8): 1.80 +/- 0.52 %ID/g, p < 0.009; radiotherapy (n = 7): 0.81 +/- 0.07 %ID/g, p < 0.02], compared to the control group (n = 10) (0.57 +/- 0.05 %ID/g). Tumor-to-muscle (T:M) and tumor-to-blood (T:B) ratios were significantly higher in both chemotherapy-treated (p < 0.02 and p < 0.01) and radiotherapy-treated cohorts (p < 0.05 and p < 0.03), compared to the control cohorts at 4 hours postinjection of (99m)Tc-Annxin V. In the post-therapy cohorts, the immunohistochemistry studies indicated a statistically significant correlation between tumor uptake of (99m)Tc-HYNIC-Annexin V and the extent of apoptosis detected by TUNEL-positive staining (r(2) = 0.41). The physiologic localization of the agent was found mainly in the kidneys (34%), liver (11%), and urine (22%). The results suggest that (99m)Tc-HYNIC-Annexin V may be an ideal agent for imaging apoptosis in response to treatment in a thymoma tumor bearing mouse model.

Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate.

BACKGROUND: There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. METHODS: (99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM. RESULTS: Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 +/- 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of (99m)Tc-PAM increased after 24 h of application to 2.4 +/- 0.15, 1.53 +/- 0.09, 7.94 +/- 0.99, and 13.2 +/- 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 +/- 0.03 and 0.22 +/- 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 +/- 0.07 and 0.16 +/- 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h. CONCLUSIONS: The results indicate that the bone uptake of (99m)Tc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.