Biokinetics of FDG after intrathecal administration

Objectives Intrathecal administration of therapeutics is promising for the treatment of diseases involving CNS and meninges. The potential of the method has not been fully realized, largely because there is still no clarity with respect to the mechanistic factors governing the biokinetics in the cerebrospinal fluid (CSF). One of the challenges relates to the difficulties in measuring the fraction of the administered drug that can be delivered into the brain from CSF through the periarterial spaces. The goal of the present study was to investigate the entrance and retention of ¹⁸FDG, an agent with excellent intracellular retention after the uptake, into the brain from the cerebrospinal fluid.

Methods Rhesus monkeys were anesthetized with isofluorane/N2O2 and positioned prone on the imaging bed of a custom Siemens focus 220 PET/CereTom CT system. Approximately 2.0 mCi of ¹⁸FDG was administered by direct injection into cisterna magna. Whole body images were acquired at 5 min per position at several time points. Images were reconstructed using the OSEM 3D/MAP algorithm and ROIs selected manually. The images and numerical data were compared with those for IV administration of 18FDG.

Results The data demonstrated ¹⁸FDG accumulation in the CNS, concurrently with exit from the CSF and accumulation in all organs and tissues, the latter as after IV administration. The patterns of FDG uptake after the IT and IV administration in CNS were similar, suggesting that a significant part of the CNS uptake was from the systemic circulation rather than from CSF. The kinetics of ¹⁸FDG exit to the system was in agreement with the rate of CSF replacement. The data were further processed to determine the fraction entering CNS from the CSF.

Conclusions ¹⁸FDG administration IT provides helpful data for understanding of the entrance of intrathecally administered drugs to CNS, and for the estimation of the maximal fraction of the administered drug that can be delivered to the brain by this route.

Research Support Shriners Hospital for Children