Assessment of Treatment Response by Autoradiography with 14C-Aminocyclopentane Carboxylic Acid, 67Ga-DTPA, and 18F-FDG in a Herpes Simplex Virus Thymidine Kinase/Ganciclovir Brain Tumor Model

摘要: Assessments of herpes simplex virus 1 thymidine kinase (HSVtk)/ganciclovir (GCV) treatment response, early in the course therapy, are important evaluation and clinical management patients. This study addresses whether imaging amino acid transport, glucose utilization, passive vascular permeability provides an indication response can predict long-term outcome. Methods: Fischer 344 rats with intracerebral HSV-tk transduced RG2TK xenografts were studied. GCV-treated (50 mg/kg twice daily) saline-treated control animals compared; triple-label quantitative autoradiography was performed 3 d after initiating treatment, survival determined. Autoradiograms 18F-FDG, 67Ga-diethylenetriaminepentaacetic (67Ga-DTPA), 14Caminocyclopentane carboxylic ( 14 C-ACPC) obtained; measurements 14C-ACPC 67Ga-DTPA plasma clearance (K1), C-ACPC transport relative utililization (R), normalized radioactivity (% dose/g) obtained tumor brain tissues. Adjacent sections stained to detect apoptotic cells, microvessels, type L neutral transporter normal brain. Results: GCV reduced K1 % dose/g 30% that nontreated (from 34 9 [mean SD] 9.5 2.7 L/min/g from 0.28 0.09 0.11 0.04 dose/g, respectively). had a significant but substantially smaller effect than toxicity on utilization little or no xenografts. These differences could not be explained by concentration at time study. Histology revealed large fraction dead cells only sparse distribution tumors. Many CD34-positive endothelial tumors showed weak marginal LAT1 staining, whereas CD98 staining remained unchanged. Survival significantly increased 18 4t o 56 17 d. Conclusion: influx, ACPC , facilitated good indicators HSV-tk/GCV gene therapy. The parametric images changes substantial better corresponding measures same tissue (tumor) regions 67 Ga-DTPA F-FDG. Amino may surrogate paradigm monitor