alexa Investigation Of Folate Receptor Targeted Imaging Of Ovarian Cancer With Newly 68Ga-labelled Folate Dimer: 68Ga-DOTA-FA2
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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4th World Congress on Cancer Science & Therapy
October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Guoqiang Shao
ScientificTracks Abstracts: J Cancer Sci Ther
DOI: 10.4172/1948-5956.S1.033
Backgroud and Aim: Ovarian cancer is the leading cause of death among women with gynecologic malignancies. The survival rate has remained low largely because of difficulties of an early diagnosis. The high-affinity folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates because of its frequent over expression in ovarian cancer but limited expression in normal human tissues and organs. Folate monomer, commonly used for folate receptor targeted imaging, demonstrate relatively low tumor uptake and high kidney accumulatioin. We prepared 68Ga-DOTA-FA2 with the aim to optimize its biodistribution and increase tumor uptake. Methods: 68Ga-DOTA-FA2 was synthesised straightforward and its stability experiments were conducted in plasma. Cell uptake studies were performed on FR-positive SKOV3 Ovarian cancer cells. Biodistribution studies were performed in nude mice bearing SKOV3 ovarian tumors 1, 2, 4h after administration of 68Ga-DOTA-FA2 or 68Ga-DOTA-FA monomer. MicroPET-CT imaging were carried out in nude mice bearing SKOV3 ovarian tumors or FR-negative A549 lung cancer 2h after tail vein injection of 68Ga-DOTA-FA2. All animals accepted folate-free diet for 2 weeks. Results: 68Ga-DOTA-FA2 was synthesised at a specific activity of 25MBq/nmol, a radiochemical yield of more than 95%. It was stable with radioactive purity of (96.3?1.5) over 4h in plasma. SKOV3 cells uptake and internalization of 68Ga-DOTA-FA2 was FR specific. This is confirmed by the biodistribution data. In biodistribution studies tumor uptake of 68Ga-DOTA-FA2 in SKOV3 group was (11.07?1.83)%ID/g at 2h and (12.19?1.72)%ID/g at 4h. They were higher than that of 68Ga-DOTAFA (7.36?1.28)%ID/g at 2h and (9.72?2.04)%ID/g at 4h. Retention of 68Ga-DOTA-FA2 in kidneys at 4h after injection (49.3?11.02%)ID/g was lower than that of 68Ga-DOTA-FA (78.5?18.33)%ID/g. MicroPET-CT imaging demonstrated significantly higher tumor accumulation of 68Ga-DOTA-FA2 in SKOV3 ovarian tumors (10.18?1.52)%ID/g than that in A549 lung cancer (2.25?0.92)%ID/g. Conclusions: 68Ga-DOTA-FA2, with higher tumor uptake and less undesired accumulation in kidneys than FA monomer, was potential for targeted imaging of FR-positive ovarian tumors.
Guoqiang Shao completed his PhD in Nanjing Medical University from 2009 to 2012. He further studied in Shuang Liu`s Lab in Purdue University as visiting Scholar from May 2011 to March 2012. He took part in several research project in targeted brachytherpy with biodegradable seeds encapsulating 32P-Chromic phophate. His interest focused on integrin αvβ3, folate and prostate specific membrane antigen receptor targeted tumor imaging and therapy. Two of his grants were funded by the Natural Science Foundation of China (NSFC) and of Jiangsu Province.
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