© 2004 by Society
© 2004 by the Society forNeuro-Oncology
Comparative pharmacokinetics of 14C-sucrose in RG-2 ratgliomas after intravenous and convection-enhanced delivery
Northwestern University Institute for Neuroscience(M.V., E.W.-Y.K., Y.N., A.E., D.R.G.) and Departmentof Neurobiology and Physiology (M.V., E.W.-Y.K., D.R.G.), NorthwesternUniversity, Evanston, IL 60208; and Department ofNeurology, Northwestern University Medical School, Evanston NorthwesternHealthcare, Evanston, IL 60201 (M.J.A., C.V.A., D.R.G.); USA
2 Send correspondence to Dennis R. Groothuis, Department of Neurology, EvanstonNorthwestern Healthcare, 2650 Ridge Avenue, Evanston, IL 60201, USA(drgroothuis{at}northwestern.edu).
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Abstract |
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We compared tissue and plasma pharmacokinetics of 14C-sucrose insubcutaneous RG-2 rat gliomas after administration by 3 routes, intravenousbolus (IV-B; 50 µCi over 30 s), continuous IV infusion (IV-C, 50 µCi ata constant rate), and convection-enhanced delivery (CED, 5 µCi infused at arate of 0.5 µl/min), and for 3 experimental durations, 0.5, 2, and 4 h.Plasma, tumor, and other tissue samples were obtained to measure tissueradioactivity. Plasma radioactivity in the CED group increased exponentiallyand lagged only slightly behind the IV-C group. After 90 min, plasma valueswere similar in all. Mean tumor radioactivity was 100 to 500 times higher inthe CED group at each time point than in the IV-B and IV-C groups. Tumorradioactivity was homogeneous in the IV groups at 0.5 h and inhomogeneous at 1and 2 h. In CED, radioactivity distribution was inhomogeneous at all 3 timepoints; highest concentrations were in tissue around tumor and in necrosis,while viable tumor contained the lowest and sometimes negligible amounts ofisotope. Systemic tissue radioactivity values were similar in all groups.Efflux of 14C-sucrose from tumors was evaluated in intracerebraltumors (at 0.5, 1, 2, and 4 h) and subcutaneous tumors (at 0 to 0.5 h). Lessthan 5% of 14C activity remained in intracerebral tumors at eachtime point. The efflux half-time from the subcutaneous tumors was 7.3 ±0.7 min. These results indicate rapid efflux of drug from brain tumor andmarked heterogeneity of drug distribution within tumor after CEDadministration, both of which may be potentially limiting factors in drugdelivery by this method.
Received August 5, 2003; Accepted October 28, 2003
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