Assessment of radiopharmaceuticals to determine hypoxia in cells and tumors of B16F10 murine melanoma

• Grant number: 11/10565-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2011
• End date: July 31, 2013
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Carlos Alberto Buchpiguel
• Grantee: Carlos Alberto Buchpiguel
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Fabio Luiz Navarro Marques ; Roger Chammas

Abstract

The low oxigenation (hypoxia) drastically changes the cell metabolism and the production way of ATP, changing various intracell parameters. Due the tumor growing and the formation of aberrant vessels, there are a vicious cicle of hypoxia-normoxia to order to suply nutritional needs of the cells; this phenomenon calls "intermittent hypoxia". This stimulates and allows cells to develop leakage, adaptation and resistance mechanisms, contributing not only to a malignat and agressive behaviour by these cells, but also giving them some resistance to a chemotherapeutic and radiotherapeutic treatments. Detection of hypoxia areas in tumoral cells can be realized with a differents radiopharmaceuticals, some them developed to be uptaken or metabolized due to some of these changings in hypoxic cells. The proposal of this work is to prepare and evaluate the behaviour of the radiopharmaceuticals (18F)FAZA, [[99mTc](O)HL91] and [[99mTc]glucarato]- on B16F10 murine melanoma. Radiopharmaceuticals will have the cellular uptake assessed after incubation of them with these cell line in culture, and, later will be used to detection of hypoxic areas in tumours, implanted on mouses, through the image formation by a PET/SPECT/CT device. The uptake rate measured by imaging techniques will be correlated with biochemistry (pH, lactic acid), immunohistochemical (HIF1, Glut1, etc) and histo pathological data (vascularization on uptaken area and cell changing, resulting from oxygen deprivation). At the end of this project, we hope to correlate the radiopharmaceuticals uptake rate and the changes seen in cells, through the different techniques. Establishing, thus, new guidelines and procedures for further studies and development of new radiopharmaceuticals. (AU)