(C-11)-thymidine PET imaging as a measure of DNA synthesis rate: A preliminary quantitative study of human brain glioblastoma
- Johns Hopkins Medical Inst., Baltimore, MD (United States); and others
(C-11)-Thymidine (TdR) PET imaging can potentially be used to measure the tumor proliferation in-vivo and monitor treatment. Twenty-four stereotactic brain biopsies (SBB) following in-vivo bromodeoxyuridine (BUDR) under MRI guidance were obtained to correlate with TdR PET imaging of primary glioblastoma in human brain. Following data acquisition, standard 4 by 4 pixel (2mm/pixel) regions of interest (ROIs) were placed over the tumor site based on SBB and the corresponding homologous region of contralateral normal cortices. After correcting input function for major metabolites and subtracting TdR activity in the normal side from the tumor side of the brain, 2- and 3- compartmental analysis was performed for all the ROIs. Akaike :(AIC) and Bayes (BIC) information criteria was calculated to compare these 2 kinetic models for differentiating pure blood pool effects from TdR incorporation into DNA. Of 24 SBB regions, 20 non-overlapping and corresponding ROIs in PET were identified and quantified. Eight ROIs were selected based on the AIC, BIC and root-mean-square errors (RMSE < 0.1) (4 couldn`t be modelled and 8 most likely represented blood flow effects). The percentage (%) of BUDR per high power field area %BUDR labelling. The k3, the forward phosphorylation rate (hence an index of DNA synthesis), was categorized into 2 groups according to a threshold value of %BUDR/hpfa - 5%. The tumor regions with low proliferative index (%BUDR/hpfa<5%) have significantly lower k3 than those with high proliferative index (p<0.005). We also find that k4 is at least an order less than k3, suggesting minimal effects of dephosphorylation and efflux of metabolites. We conclude that 3-compartmental, 4-parameter modeling is adequate for TdR PET studies and k3 correlates with DNA synthesis rate.
- OSTI ID:
- 197890
- Report Number(s):
- CONF-940605-; ISSN 0161-5505; TRN: 95:007029-0013
- Journal Information:
- Journal of Nuclear Medicine, Vol. 35, Issue Suppl.5; Conference: 41. annual meeting of the Society of Nuclear Medicine, Orlando, FL (United States), 5-8 Jun 1994; Other Information: PBD: May 1994
- Country of Publication:
- United States
- Language:
- English
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