Factors affecting tumor (18) F-FDG uptake in longitudinal mouse PET studies

BACKGROUND: Many biological factors of 2-[(18) F]fluoro-2-deoxy-d-glucose ((18) F-FDG) in blood can affect (18) F-FDG uptake in tumors. In this study, longitudinal (18) F-FDG positron emission tomography (PET) studies were performed on tumor-bearing mice to investigate the effect of blood glucose level and tumor size on (18) F-FDG uptake in tumors. METHODS: Six- to eight-week-old severe combined immunodeficiency mice were implanted with glioblastoma U87 (n = 8) or adenocarcinoma MDA-MB-231 (MDA) (n = 11) in the shoulder. When the tumor diameter was approximately 2.5 mm, a 60-min dynamic (18) F-FDG PET scan was performed weekly until the tumor diameter reached 10 mm. Regions of interests were defined in major organs and tumor. A plasma curve was derived based on a modeling method that utilizes the early heart time-activity curve and a late-time blood sample. The (18) F-FDG uptake constant K(i) was calculated using Patlak analysis on the tumors without an apparent necrotic center shown in the PET images. For each tumor type, the measured K(i) was corrected for partial volume (PV), and multivariate regression analysis was performed to examine the effects of blood glucose level ([Glc]) and tumor growth. Corrected Akaike's information criterion was used to determine the best model. RESULTS: The regression model that best fit the PV-corrected K(i) for U87 data was K(i)/RC = (1/[Glc]) × (0.27 ± 0.027) mL/min/mL (where [Glc] is in mmol/L), and for MDA, it was K(i)/RC = (0.04 ± 0.005) mL/min/mL, where K(i)/RC denotes the PV-corrected K(i) using an individual recovery coefficient (RC). The results indicated that (18) F-FDG K(i)/RC for U87 was inversely related to [Glc], while [Glc] had no effect on (18) F-FDG K(i)/RC of MDA. After the effects of PV and [Glc] were accounted for, the data did not support any increase of (18) F-FDG K(i) as the tumor (of either type) grew larger in size. CONCLUSIONS: The effect of [Glc] on the tumor (18) F-FDG K(i) was tumor-dependent. PV- and [Glc]-corrected (18) F-FDG K(i) did not show significant increase as the tumor of either type grew in size.