Faculty Collaboration Database

Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery. Neuro Oncol 2004 Apr;6(2):104-12

Date

05/12/2004

Pubmed ID

15134624

Pubmed Central ID

PMC1871980

DOI

10.1215/s1152851703000449

Scopus ID

2-s2.0-1842588861 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

We compared tissue and plasma pharmacokinetics of 14C-sucrose in subcutaneous RG-2 rat gliomas after administration by 3 routes, intravenous bolus (i.v.-B; 50 microCi over 30 s), continuous i.v. infusion (i.v.-C, 50 microCi at a constant rate), and convection-enhanced delivery (CED, 5 microCi infused at a rate of 0.5 microl/min), and for 3 experimental durations, 0.5, 2, and 4 h. Plasma, tumor, and other tissue samples were obtained to measure tissue radioactivity. Plasma radioactivity in the CED group increased exponentially and lagged only slightly behind the IV-C group. After 90 min, plasma values were similar in all. Mean tumor radioactivity was 100 to 500 times higher in the CED group at each time point than in the i.v.-B and i.v.-C groups. Tumor radioactivity was homogeneous in the i.v. groups at 0.5 h and inhomogeneous at 1 and 2 h. In CED, radioactivity distribution was inhomogeneous at all 3 time points; highest concentrations were in tissue around tumor and in necrosis, while viable tumor contained the lowest and sometimes negligible amounts of isotope. Systemic tissue radioactivity values were similar in all groups. Efflux of 14C-sucrose from tumors was evaluated in intracerebral tumors (at 0.5, 1, 2, and 4 h) and subcutaneous tumors (at 0 to 0.5 h). Less than 5% of 14C activity remained in intracerebral tumors at each time 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 and marked heterogeneity of drug distribution within tumor after CED administration, both of which may be potentially limiting factors in drug delivery by this method.

Author List

Vavra M, Ali MJ, Kang EW, Navalitloha Y, Ebert A, Allen CV, Groothuis DR

Author

Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Brain Neoplasms
Carbon Radioisotopes
Drug Delivery Systems
Glioma
Infusions, Intravenous
Injections, Intravenous
Rats
Rats, Inbred F344
Sucrose
Tissue Distribution
Xenograft Model Antitumor Assays