Longitudinal microPET/CT imaging of brain tumor growth with ¹⁸F-FET

Objectives To non-invasively follow and characterize brain tumor growth by ¹⁸F-FET PET in a preclinical tumor model.

Methods In vivo uptake of ¹⁸F-FET was followed by weekly serial microPET imaging scans to follow incubation time and tumor growth as a function of time. Human glioblastoma cells (NGBM_CPH048p6, 10⁵ cells)¹, were injected orthotopic in athymic nude mice (n=20). Mice were followed 11 weeks after cell inoculation. Ten min static images were obtained at 20-30 min postinjection of approximately 10 MBq ¹⁸F-FET in the tail vein. Images were reconstructed using the maximum a posteriori (MAP) algorithm. Circular regions of interest were placed at the location of maximum tracer uptake in the tumor and in the contralateral hemisphere (reference region). Tracer uptake was expressed as tumor-to-brain ratio of SUV_max.

Results A tumor-to-brain ratio of 1.25 or above was found to be the cutoff value defining the shift from incubation period to exponential tumor growth. The incubation period ranged from 3-11 (n=16) weeks (median =6 weeks) and the tumor growth period ranged from 2-3 weeks (median=3 weeks) before mice were euthanized due to weight loss or other brain tumor symptoms. A statistically significant increase in the tumor-to-brain ratio was detected every week in the tumor growth period.

Conclusions This study demonstrates the feasibility of using ¹⁸F-FET microPET to follow tumor growth in a preclinical setting. The cutoff value defining the shift to exponential tumor growth can be used to decide when to include a specific mouse in a treatment study. Further investigations are necessary to elucidate if ¹⁸F-FET can be used for monitoring therapy efficacy in human glioblastoma xenografts.

Research Support This study was financially supported by the Danish Cancer Society.