In Vivo Anti-carcinoma Effect Of ～(90)Y-DOTATATE And Its Influence On The Expression Of Apoptosis Inhibitor Survivin

Primary hepatocellular carcinoma (HCC) is a malignant tumor of digestion system,which incidence is the 3rd high of all the malignancy.It is lack of a efficient treatment of HCC exept for surgery.However,HCC that can receive surgery resect is less than 25% due to the factors such as indications of surgery and stages of the tumor. Conventional external radiotherapy, one of important method in treatment hepatocellular carcinoma, has not a limited factor owing to the confine of free from anatomic site, and no suffer multi-or permeate tumors focal confine either. However, radiotherapy has a very limited role in the treatment of HCC because of the accompanying liver tissue, due to liver cancer is insensitive tumors and radical cure dosage at least considered need for 60Gy, leading to hepatic fibrosis. The local control of tumor was required high radiation dose. However, the irradiated dosage have clearly exceeded the tolerance dose of intact liver tissues, moreover, majorityclinic patients have the hepatocirrhosis and sometimes staging late, so hold large-volume high dose of treatment easy bring radioactivity hepatitis. Seeing intact liver tolerance dose confine, conventional external radiotherapy has only a role of restrain timorous appeasement in HCC.A better way to treat HCC with irradiation,at least theoretically,is to use targeted internal radiation therapy. Radionuclead labeled ligand (include hormone, neurotransmitter and receptor excitant or blocking agent), which possess high specificity, high selectivity and high affinity while combine with receptor as the targeting medicament, could exert internal radiation on the tumour with high density expressive homologize receptor. Targeted therapy has shown huge vitality and become a soprano behalf by some biological active peptide receptor mediated the targeting medication since nineties. There are tens of species somatostatin analogues, like octreotide and RC-160, have synthesized for the moment. It has been widely reported the growth suppressing function of somatostatin and its analogs on many tumors. Like most neuroendocrine tumors, adenocarcinomas originating in the breast, colon, or pancreatic tumor, as well as meningiomas, express somatostatin receptors, and the majority of these tumors express the somatostatin receptor subtype2. Many test recently manifested that radiolabeled somatostatin analogues could prominently suppress proliferation of somatostatin receptor-positive tumors, like neuroendocrine tumour, prostatic cancer,cancer of pancreas, breast cancer and small-cell carcinoma of the lung, and have opened new prospects in nuclear oncology for diagnosis and therapy.Yttrium 90 is a sort of radionuclide by ⁹⁰Sr-⁹⁰Y radionuclide generators systems. Thereof half life for 64.0 hour, the average energy for 0, 9314mev of the beta particle, maximal organize penetrating power less than 1cm, average penetrating power for 0.25cm beta particle, ceiling energy to 2.27Mev. Due to ⁹⁰Y possess feasible half life, without gamma ray, labeled stabilize, and moderate energy beta ray as well, in addition, ⁹⁰Y fit labeled to bifunctional chelators (BFCs)diethylenetriaminepentaacetic acid ( DTPA ) and tetraazacyclodo-decanetetraacetic acid (DOTA) became the stable chelate, hence, in recent years people have usually used ⁹⁰Y for labeled somatostatin analogues for targeted internal radiotherapy. Meanwhile, it has been demonstrated previously that ⁹⁰Y labeled somatostatin analogue significantly inhibited the growth of somatostatin receptor-positive tumors in many in vivo trials.Survivin, a novel IAP (inhibitor of apoptosis IAP) , was discovered recently by the hybridization screening of human genomic libraries with the cDNA of a factor Xa receptor, effector cell protease receptor-1 (EPR-1). Overexpression of survivin was observed in all the most common human cancers by analysis of its transcript and protein. Survivin,compared with other members of the IAP family, is characterized by a unique structure, by its involvement in the regulation of the cell cycle, and by th...