Somatostatin Receptor-Mediated ～(90)Y-DOTA-Tyr～3-octreotide [～(90)Y-DOTATATE] Targeting Internal Radiotherapy And /or Not Conventional External Radiotherapy In Hepatocellular Carcinoma Bearing BABL/c Nude Mice

Hepatocellular carcinoma (HCC) is the third most common cancers in China, with a worldwide incidence between 250,000 and 1,000,000 new cases per year, and there are many difficulties in treatment of HCC. Surgical resection is generally accepted as the first choice of treatment for HCC, but only a small proportion of patients are candidate for radical resection at the time of diagnosis. Recent advances of surgical technique and perioperative care have resulted in a reduction in operative morbidity and mortality even in cirrhotic patients and a 5-year survival rate of 40% can be achieved. However, due to its multifocal nature and association with cirrhosis at a rate of more than 80%, only about 20% of all patients with HCC are considered resectable at initial presentation. For most non-resectable patients the need of an elective non-surgical treatment, like radiotherapy, transcatheter arterial chemoembolization (TACE), hormonal and radiofrequency therapy are obvious. In general, transcatheter arterial chemoembolization (TACE) is generally considered to be an effective treatment mondality for non-resectable patients with HCC, and 1- to 5-year survival rates were 51%, 28%, 13%, 8%, and 6%, respectively. Although radiotherapy is one of important method and the most effective modalities for treating malignant neoplasms of various sittes, it is used infrequently to treat primary hepatocellular carcinoma (HCC). Conventional external radiotherapy has an unlimited factor of anatomic site and multi-or permeates tumors focal for treating HCC. However, radiotherapy has a very limited role in thetreatment of HCC owing to liver cancer is insensitive tissue of irradiation and results in radioactivity hepatitis in patients with HCC, which the local control of tumor was required high radiation dose and clearly exceeded the tolerance dose of intact liver tissues as radical cure dosage at least considered need for 60Gy for HCC. Conventional external radiotherapy has only a role of appeasement in HCC. The roles of somatostatin analogues, especially radioactive isotopes labelled octreotide (a somatostatin analogue) have more and more pay close attention to treating HCC.It is one of hotspot that targeting therapy by radioactive isotopes labelled octreotide (a somatostatin analogue) in oncology. Targeting therapy was defined that using the molecule with special affinity to certain histiocyte of neoplasm as the carrier, and then medicament coupled should thereof directive feed to acting target organ foci region. This method of treatment was applied by the radioactive medicament which as high selectivity, specificity, and high affinity to receptor (somatotropin receptor. The superiority of radioactive medicament is easy synthesize, small molecular weight (1000kd or so), so it have fast blood clear up, strong penetrating, best targetting, and long maintenance at tumour tissue. 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. A previously experiment shown that high expression SSTR₂ and (125)^I lablled octreotide have got sharp upstake in HCC tissues. Although a previously study confirmed that nonlablled octreotide could treat HCC in 1990s, radiolabeled somatostatin analogues used treating HCC have not developed at all times. In addition, radiolabeled somatostatin analogues (octreotide) are testing, so there are many questions on the stability and tissues distribution of the radiochemic drug in the air when targeting internal radiotherapy. In this background, we have developed targeted radiotherapy using radionuclead 90-yttrium conjugated bifunctional chelators (BFCs) based on tetraazacyclododecanetetraacetic acid (DOTA) and targeted internal radiotherapy plus synchro-conventional external radiotherapy for treatment of primary carcinoma of liver in bea...