⁹⁹tc^m-dota-noc As A New Radiolabeling Ssta For The Detection Breast Cancer In Nude Mice Tumor Model And Correlation With Sstr Expression

Objective Radionuclide labeling low molecular weight polypeptide is hotspot for the diagnosis and treatment of malignant tumor. The purpose of this work is to study a ⁹⁹Tc_m labeling method for the third-generation somatostatin analogue DOTA-NOC and evaluate the radiochemical purity and stability of ⁹⁹Tc_m-DOTA-NOC, observe its biodistribution and metabolism in mice, observe the tumor uptake of ⁹⁹Tc_m-DOTA-NOC, and evaluate the correlation between the expression of somatostatin receptor (SSTR) in tumor and the ⁹⁹Tc_m-DOTA-NOC scintigtaphy of breast cancer.Metheds Employing the parallel peptide synthesis approach by further exchanging the amino acid in position 3 of octreotide and coupling the macrocyclic chelator DOTA(1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) to these peptides for labelling with radiometal -s ⁹⁹Tc_m. The labeled product was identified with high performance liquid chromatography (HPLC) and the labeling yield an radiochemical purify were measured by paper chromatography(PC). Kill the mice at differents time , determine the radiocounting of blood and organs, and take out the %ID/g and studied the biodistribution and metabolism. Nude mice bearing human MDA-MB-435 breast cancer model was established, ⁹⁹Tc_m-DOTA-NOC imaging was performaed, and the ratio of tumor to normal tissue (T/NT) was calculated over ROI to observe the radioactive uptake. The biodistribution was studied. The mRNA expression of SSTR in tumor tissue was detected by RT-PCR to evaluate the correlation between the expression of SSTR in tumor tissue and the ⁹⁹Tc_m- DOTA- NOC scintigraphy of breast cancer.Results The reaction condition of ⁹⁹Tc_m-DOTA-NOC is pH 4.1,0.2mol/L 115μl of Acetate buffer,DOTA-NOC5μl(5μg),⁹⁹Tc_mO4100μl(148MBq),SnCl2·Hcl30μl(30μg),temperature is 50℃and reaction time is 45min, The instant radiochemical purity was 95%,and the radiochemical purity was remaind 90% after 6h. Results of biodistribution in normal Kunming mice studies shown that the highest radioactively levels were in the liver and kidneys [(12.41±1.42)%ID/g and (5.15±054)%ID/g, respectively]. The distribution in human breast tumor-bearing mice was similar to it in normal Kunming mice. Static planar imaging showed that the tumor had focal uptake of ⁹⁹Tc_m-DOTA-NOC. Four hours after ⁹⁹Tc_m-DOTA-NOC administration, the T/NT ratio was 2.41±0.21. The biodistribution showed high uptake of the tracer in tumor; high expression of SSTR3 and SSTR2 in breast cancer, epecially SSTR3. Positive correlation were obtained between the T/NT ratio and the expression of SSTR3 and SSTR2 mRNA (r=0.94, r=0.81, respectly, P<0.05).Conclusion The third-generation somatostatin analogue DOTA-NOC could be labeled effectively with ⁹⁹Tc_m by the method presented in this paper, with good yield, radiochemical purity and stabilit. ⁹⁹Tc_m-DOTA-NOC could induce tumor apoptosis and inhibit the tumor cell of breast cancer cell. There is a significant correlation between the tumor uptake of ^99mTc-DOTA-NOC and SSTR3 and SSTR2 mRNA expression. This approach may provide a basis for SSTR targeted and therapy of human breast cancer.