The relationship between ~(99)Tc~m-MIBI uptake and cell death or proliferative activity after irradiation of tumor

Objective To evaluate the potential of 99 Tc m-MIBI imaging for monitoring cellular viability of tumor post-irradiation. Methods One hundred and five female Kunming mice bearing Ehrlich carcinoma in the left thigh were exposed to 60 Co at a single dose of 0, 5, 10, 15 and 20 Gy, respectively, and then the following protocols were performed at 6 h pre-irradiation and 24, 72, 144 h post-irradiation, respectively (every group with different irradiation dose or observation time consisted of six to eight mice): ① 99 Tc m-MIBI planer scintigraphy was performed, then the tumor sample was excised and its radioactivity was counted in a γ counter. Differential uptake ratio (DUR) and tumor-to- nontarget (T/NT) ratio were used to quantitate the MIBI uptake. ②Single-cell suspension of tumor was prepared and apoptosis index (AI) was measured by flow cytometry; meanwhile, paraffin sections were stained with HE or proliferating cell nuclear antigen (PCNA) immunohistochemistrily, then percentages of necrosis area (PNA) and PCNA integral absorbance (PCNA-IA) were measured with a HPIAS-1000 imaging analysis system. Results ①Compared with the group with 0 Gy, the DUR of the groups with 10, 15, 20 Gy decreased markedly starting from 24 h post-irradiation and the decrease of DUR in 5 Gy group was much milder. Within the groups with similar irradiation dose, DUR kept decreasing with the time past irradiation. At the same post-irradiation time point, DUR decreased with dose escalating. The change of T/NT was similar to DUR. There was a perfect linear correlation between DUR and T/NT ( n=105, r=0.976, P 0.01). ②Compared with the group with 0 Gy, at 24 h post-irradiation, the AI and PNA in other groups increased but PCNA-IA decreased with dose escalating. However, at 72 and 144 h post-irradiation, AI reversed to the same level as in 0 Gy group and PCNA-IA rose close to the level of 0 Gy group, but PNA increased continuously. At the same time point, PNA increased with dose escalating. ③At 24 h post-irradiation, DUR or T/NT was negatively correlated with AI or PNA ( n=33, r =-0.849, -0.829; -0.883, -0.855, respectively, P 0.01) and positively correlated with PCNA-IA ( n=33, r= 0.789, 0.742, respectively, P 0.01). At 72 and 144 h post-irradiation, DUR or T/NT was only negatively correlated with PNA ( n=33, r= -0.967, -0.956; -0.915, -0.886, respectively, P 0.01). Conclusions 99 Tc m-MIBI uptake of tumor cells correlated with the changes of cell viability after irradiation. 99 Tc m-MIBI imaging may be helpful to monitoring tumor cell viability or therapeutic response after irradiation.