A non-invasive technique to image tumor cell proliferation would have immedicate clinical utility. It would be used in the evaluation of tumor growth potential and grade of malignancy; it would identify the most rapidly proliferating regions of the tumor and provide spatial information for radiation treatment planning and stereotactic biopsies and surgical resections; and it would provide a new and more relevant measure of treatment response which could identify treatment 'success' or 'failure' much earlier than changes in tumor size or volume identified with CT or MR, or changes in glucose metabolism identified with positron emission tomography (PET). The potential for obtaining functional images of DNA synthesis using radiolabeled pyrimidine nucleosides and PET or SPECT has been recognized for some time. Two limitations have been recognized in these studies: 1)low incorporation of radiolabeled precursors into DNA of dividing cells; and 2) the presence of radiolabeled metabolites that can confound the interpretation of the images. This proposal addresses both issues by using a long-lived radioisotope ([124I], t1/2=4 days)to label the precursor molecule (iododeoxyuridine; IudR), and highly efficient PET imaging (positron emission tomography; septa-out) 24 hours after [124]-IUdR administration to allow for 'washout' of radiolabeled metabolites prior to imaging. We have demonstrated for the first time that good quality PET images of [124]-IUdR uptake and retention can be obtained in patients with brain tumors, and that the location of high [124]-IUdR uptake in malignant brain tumors does not necessarily correspond to the lcation of high glucose metabolic activity measured with [18F]-fluorodeoxyglucose ([18F]-FDG) in the same tumor. This proposal seeks to validate that tumor proliferation can be reliably imaged with [124]-IUdR and PET.
Aim 1 seeks to determine dosimetry to critical tissues and organs, to evaluate the 'washout strategy' in order to determine the optimal time post injection at which to image.
Aim 2 seeks to confirm that the activity measured by PET after the washout period is predominantly due to [124]-IUdR incorporated into DNA, and that the level of this activity correlates with other measures of tumor proliferation and patient survival.
Aim 3 seeks to compare the pattern and magnitude of [124]-IUdR uptake in malignant brain tumors with that of [18F]-FDG and also to directly compare the degree of correlation of the IudR and FDG results with tumor grade and patient survival.
