Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer

David Croteau, Stuart Walbridge, Paul F. Morrison, John A. Butman, Alexander Vortmeyer, Dennis Johnson, Edward H. Oldfield, Russell R. Lonser

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Object. Convection-enhanced delivery (CED) is increasingly used to distribute therapeutic agents to locations in the central nervous system. The optimal application of convective distribution of various agents requires the development of imaging tracers to monitor CED in vivo in real time. The authors examined the safety and utility of an iodine-based low-molecular-weight surrogate tracer for computerized tomography (CT) scanning during CED. Methods. Various volumes (total volume range 90-150 μl) of iopamidol (MW 777 D) were delivered to the cerebral white matter of four primates (Macaca mulatta) by using CED. The distribution of this imaging tracer was determined by in vivo real-time and postinfusion CT scanning (≤ 5 days after infusion [one animal]) as well as by quantitative autoradiography ( 14 C-sucrose [all animals] and 14 C-dextran [one animal]), and compared with a mathematical model. Clinical observation (≤ 5 months) and histopathological analyses were used to evaluate the safety and toxicity of the tracer delivery. Real-time CT scanning of the tracer during infusion revealed a clearly definable region of perfusion. The volume of distribution (V d ) increased linearly (r 2 = 0.97) with an increasing volume of infusion (V i ). The overall V d /V i ratio was 4.1 ± 0.7 (mean ± standard deviation) and the distribution of infusate was homogeneous. Quantitative autoradiography confirmed the accuracy of the imaged distribution for a small (sucrose, MW 359 D) and a large (dextran, MW 70 kD) molecule. The distribution of the infusate was identifiable up to 72 hours after infusion. There was no clinical or histopathological evidence of toxicity in any animal. Conclusions. Real-time in vivo CT scanning of CED of iopamidol appears to be safe, feasible, and suitable for monitoring convective delivery of drugs with certain features and low infusion volumes.

Original languageEnglish (US)
Pages (from-to)90-97
Number of pages8
JournalJournal of neurosurgery
Volume102
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

Convection
Molecular Weight
Tomography
Iopamidol
Dextrans
Autoradiography
Sucrose
Safety
Macaca mulatta
Iodine
Primates
Theoretical Models
Central Nervous System
Perfusion
Observation
Pharmaceutical Preparations

Keywords

  • Central nervous system
  • Computerized tomography
  • Convection-enhanced delivery
  • Drug delivery
  • Macaca mulatta

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Croteau, D., Walbridge, S., Morrison, P. F., Butman, J. A., Vortmeyer, A., Johnson, D., ... Lonser, R. R. (2005). Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer. Journal of neurosurgery, 102(1), 90-97. https://doi.org/10.3171/jns.2005.102.1.0090

Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer. / Croteau, David; Walbridge, Stuart; Morrison, Paul F.; Butman, John A.; Vortmeyer, Alexander; Johnson, Dennis; Oldfield, Edward H.; Lonser, Russell R.

In: Journal of neurosurgery, Vol. 102, No. 1, 01.01.2005, p. 90-97.

Research output: Contribution to journalArticle

Croteau, D, Walbridge, S, Morrison, PF, Butman, JA, Vortmeyer, A, Johnson, D, Oldfield, EH & Lonser, RR 2005, 'Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer', Journal of neurosurgery, vol. 102, no. 1, pp. 90-97. https://doi.org/10.3171/jns.2005.102.1.0090
Croteau, David ; Walbridge, Stuart ; Morrison, Paul F. ; Butman, John A. ; Vortmeyer, Alexander ; Johnson, Dennis ; Oldfield, Edward H. ; Lonser, Russell R. / Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer. In: Journal of neurosurgery. 2005 ; Vol. 102, No. 1. pp. 90-97.
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