Study Of The Relevance Of Uptake Of ⁹⁹Tc^m-HL91 Organization, HIF-1α Expression And Apoptosis Status Of Mouse Tumor Tissue

Objective: By analyzing the relevance of uptake of ⁹⁹Tc^m-HL91 in, HIF-1αexpression and apoptosis of mouse tumor tissue between before and after of a single chemotherapy. To explore the feasibility of using of ⁹⁹Tc^m-HL91 imaging to evaluate early apoptosis state of tumor cells after early chemotherapy .Methods: Adopt HL9l as direct labeling ⁹⁹Tc^m radionuclide tracer imaging hypoxia. Divided 20 female mice of 615 with Ca761 breast cancer into two groups randomly : the control group and the chemotherapy group, 10 in each group. Mice in chemotherapy group accept a one-time docetaxel (docetaxcel) intraperitoneal injection, a dose of 5mg/kg (0.4mg/1ml); control group of mice by intraperitoneal injection of the same volume of normal saline. 24h later, the two groups of mice have injection 37MBq (0.1ml) ⁹⁹Tc^m-HL91 by the mouse tail vein at the same time; the control group have anterior and posterior body planar imaging in 1,2,4,6,8h after injection, and chemotherapy group have imaging in 4h after injection. Calculate the radioactive ratio (T/NT) of tumor tissue (T) and corresponding contralateral site (NT) by interest Regions technology. Put all mice to death immediately after Imaging, ablate tumor tissue completely, then put the tumor tissue in formalin solution to immersion, fixed, reserved for DNA fragments in situ end labeling (TUNEL) assay of apoptosis in tumor tissue and immune histochemical detection of hypoxia-inducible factor-1α(hypoxia-inducible factor-1α, HIF-1α).Results: The two groups of mice on the tumor tissue have a better ⁹⁹Tc^m-HL91 uptake and retention, the corresponding contralateral tumor site and have a higher ratio of radioactive counts.The T/NT values 1,2,4,6,8 h in control group of mice were 1.394±0.074,1.651±0.214,2.310±0.306, 1.947±0.250, 1.749±0.400. The T/TN value (4h)of chemotherapy group were 2.018±0.189,T/TN value (4h) of two groups of compared with significant difference (t = 3.199, P = 0.024); The number of apoptotic cells, HIF-1αdetection value (the average optical density) of Control group of were 4.500±0.926, 0.010±0.004; the number of chemotherapy group were 8.900±2.132, 0.005±0.001. HIF-1αdetection values of two groups with significant difference (t = 3.199, P = 0.013); the number of apoptotic cells between two groups with a significant difference (t =- 5.871, P = 0.000). Correlation study: The detection of HIF-1αvalues with ⁹⁹Tc^m-HL91 uptake was positively correlated in control group, (r = 0.856, P = 0.007), and the number of apoptotic cells was negatively correlated (r =- 0.807, P = 0.015); and there is no clear correlation between ⁹⁹Tc^m-HL91 uptake and the number of apoptotic cells (r =- 0.572, P = 0.138). Chemotherapy group of HIF-1αdetection value of ⁹⁹Tc^m-HL91 uptake was positively correlated (r = 0.811, P = 0.004), and the number of apoptotic cells was negatively correlated (r =- 0.916, P = 0.000); ⁹⁹Tc^m-HL91 uptake and the number of apoptotic cells was negatively correlated (r = -0.682, P = 0.030).Conclusion:1. Single docetaxel chemotherapy, not only inducing a large number of tumor cells apoptosis, but also reduce the tumor tissue uptake of ⁹⁹Tc^m-HL91 and expression of HIF-1αat the same time.2. It could reflecte the HIF-1αprotein expression distribution in tumor through quantitative ⁹⁹Tc^m-HL91 in tumor tissues indirectly.3. High expression of HIF-1αmay inhibit tumor cell apoptosis.4. The use of ⁹⁹Tc^m-HL91 imaging can evaluate the tumor cells after chemotherapy in the early state of apoptosis indirectly.