Kinetics of vascular targeted monoclonal antibody.

Stephen Kennel, Ying Huang, Wen Bin Zeng, Alan Stuckey, Jonathan Wall

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

There is growing interest in delivery of drugs and radioisotopes with carriers designed to target molecular receptors in the vascular space. In contrast to targets outside of blood vessels, vascular receptors are easily accessed and tracer binding is not significantly impacted by the size of the targeted drug carrier. Although it is accepted that vascular targeting is very efficient, the kinetics of target binding in the vascular space immediately after injection has not been evaluated. MAb 201B accumulation in mouse lung, by virtue of its binding to thrombomodulin on lung endothelium, has been used as a model for imaging and vascular targeting. MAb 201B was radioiodinated with either (125)I comparing two different methods of radioiodination to assess label stability. MAb accumulation and retention were monitored after iv injection in normal BALB/c mice by standard biodistribution experiments, SPECT/CT. MAb radiolabeled with positron emitting (124)I was evaluated by dynamic microPET. The data show that lung uptake and kinetics of loss (t1/2≈40 hrs) of (125)I MAb 201B was similar with two different radio-iodination methods. Loss of radioiodine was detected in sample radiolabeled using the chloramines T method, but only at later time points(24hrs). For very short time evaluations the more efficient chloramine T method was adopted for PET studies with (124)I. Lung uptake of (124)I MAb 201B occurred within seconds of injection as observed in dynamic microPET analysis with little (124)I MAb ever detected in the peripheral circulation. In contrast, distribution kinetics of control (124)I MAb 14 or (124)I MAb 201B that had been diluted with excess cold MAb demonstrated equilibration throughout the vascular space. Accumulation of MAb targeted to epitopes in the vascular space occurs very rapidly, is highly specific and very efficient. Drug delivery with vascular targeting agents can accommodate fast acting therapeutic agents including short half lived radioisotopes.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalCurrent Drug Delivery
Volume7
Issue number5
StatePublished - Jan 1 2010

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Blood Vessels
Monoclonal Antibodies
Lung
Radioisotopes
Injections
Thrombomodulin
Drug Carriers
Halogenation
Radio
Pharmaceutical Preparations
Endothelium
Epitopes
Electrons

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Kennel, S., Huang, Y., Zeng, W. B., Stuckey, A., & Wall, J. (2010). Kinetics of vascular targeted monoclonal antibody. Current Drug Delivery, 7(5), 428-435.

Kinetics of vascular targeted monoclonal antibody. / Kennel, Stephen; Huang, Ying; Zeng, Wen Bin; Stuckey, Alan; Wall, Jonathan.

In: Current Drug Delivery, Vol. 7, No. 5, 01.01.2010, p. 428-435.

Research output: Contribution to journalArticle

Kennel, S, Huang, Y, Zeng, WB, Stuckey, A & Wall, J 2010, 'Kinetics of vascular targeted monoclonal antibody.', Current Drug Delivery, vol. 7, no. 5, pp. 428-435.
Kennel S, Huang Y, Zeng WB, Stuckey A, Wall J. Kinetics of vascular targeted monoclonal antibody. Current Drug Delivery. 2010 Jan 1;7(5):428-435.
Kennel, Stephen ; Huang, Ying ; Zeng, Wen Bin ; Stuckey, Alan ; Wall, Jonathan. / Kinetics of vascular targeted monoclonal antibody. In: Current Drug Delivery. 2010 ; Vol. 7, No. 5. pp. 428-435.
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