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Direct, Quantitative, and Noninvasive Imaging of the Transport of Active Agents Through Intact Brain with Positron Emission Tomography

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Abstract

Purpose

Our goal was to use positron emission tomography (PET) to analyze the movement of radiolabeled agents in tissue to enable direct measurement of drug delivery to the brain.

Procedures

Various 11C- and 18 F-labeled compounds were delivered directly to an agarose phantom or rat striatum. Concentration profiles were extracted for analysis and fitted to diffusion models.

Results

Diffusion coefficients ranged from 0.075 ± 0.0026 mm2/min ([18 F]fluoride ion, 18 Da) to 0.0016 ± 0.0018 mm2/min ([18 F]NPB4-avidin, 68 kDa) and matched well with predictions based on molecular weight (R 2 = 0.965). The tortuosity of the brain extracellular space was estimated to be 1.56, with the tissue clearance halftime of each tracer in the brain varying from 19 to 41 min.

Conclusions

PET is an effective modality to directly quantify the movement of locally delivered drugs or drug carriers. This continuous, noninvasive assessment of delivery will aid the design of better drug delivery methods.

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Acknowledgments

The authors gratefully acknowledge the contributions of the staff of the Yale PET Center, including Maria Corsi, Krista Fowles, Jim Ropchan, Patrick Ouellette, and Nancy Nishimura for their technical assistance. This work was supported by National Institutes of Health grant, T32DA022975, “Neuroimaging Sciences Training Program” and was also made possible by CTSA Grant Number UL1RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the National Institutes of Health (NIH), and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

Conflict of Interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Diagnostic Radiology, Yale School of Medicine, New Haven, CT, 06511, USA

    Rachael W. Sirianni, Ming-Qiang Zheng, Yiyun Huang & Richard E. Carson

  2. Biomedical Engineering, Yale University, New Haven, CT, 06511, USA

    W. Mark Saltzman & Richard E. Carson

  3. Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ, 85014, USA

    Rachael W. Sirianni

Authors
  1. Rachael W. Sirianni
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  2. Ming-Qiang Zheng
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  3. W. Mark Saltzman
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  4. Yiyun Huang
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  5. Richard E. Carson
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Correspondence to Rachael W. Sirianni.

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Sirianni, R.W., Zheng, MQ., Saltzman, W.M. et al. Direct, Quantitative, and Noninvasive Imaging of the Transport of Active Agents Through Intact Brain with Positron Emission Tomography. Mol Imaging Biol 15, 596–605 (2013). https://doi.org/10.1007/s11307-013-0636-9

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  • DOI: https://doi.org/10.1007/s11307-013-0636-9

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