Magnitude of enhanced permeability and retention effect in tumors with different phenotypes: (89)Zr-albumin as a model system Journal Article


Authors: Heneweer, C.; Holland, J. P.; Divilov, V.; Carlin, S.; Lewis, J. S.
Article Title: Magnitude of enhanced permeability and retention effect in tumors with different phenotypes: (89)Zr-albumin as a model system
Abstract: Targeted nanoparticle-based technologies show increasing prevalence in radiotracer design. As a consequence, quantitative contribution of nonspecific accumulation in the target tissue, mainly governed by the enhanced permeability and retention (EPR) effect, becomes highly relevant for evaluating the specificity of these new agents. This study investigated the influence of different tumor phenotypes on the EPR effect, hypothesizing that a baseline level of uptake must be exceeded to visualize high and specific uptake of a targeted macromolecular radiotracer. Methods: These preliminary studies use 89Zr-labeled mouse serum albumin (89Zr-desferrioxamine- mAlb) as a model radiotracer to assess uptake and retention in 3 xenograft models of human prostate cancer (CWR22rv1, DU-145, and PC-3). Experiments include PET and contrast-enhanced ultrasound imaging to assess morphology, vascularization, and radiotracer uptake; temporal ex vivo biodistribution studies to quantify radiotracer uptake over time; and histologic and autoradiographic studies to evaluate the intra- and intertumoral distribution of 89Zr-desferrioxamine- mAlb. Results: Early uptake profiles show statistically significant but overall small differences in radiotracer uptake between different tumor phenotypes. By 20 h, nonspecific radiotracer uptake was found to be independent of tumor size and phenotype, reaching at least 5.0 percentage injected dose per gram in all 3 tumor models. Conclusion: These studies suggest that minimal differences in tumor uptake exist at early time points, dependent on the tumor type. However, these differences equalize over time, reaching around 5.0 percentage injected dose per gram at 20 h after injection. These data provide strong support for the introduction of mandatory experimental controls of future macromolecular or nanoparticle- based drugs, particularly regarding the development of targeted radiotracers. Copyright © 2011 the American Physiological Society.
Keywords: controlled study; unclassified drug; drug penetration; nonhuman; positron emission tomography; radiopharmaceuticals; neoplasms; mouse; phenotype; animals; mice; tumor volume; animal experiment; animal model; tumor xenograft; drug specificity; prostate cancer; prostatic neoplasms; albumin; drug distribution; drug uptake; tissue distribution; contrast enhancement; echography; positron-emission tomography; radiopharmaceutical agent; transplantation, heterologous; neoplasm transplantation; image processing, computer-assisted; ex vivo study; radioisotopes; zirconium; drug stability; deferoxamine; autoradiography; permeability; iron chelating agents; tissue perfusion; serum albumin; analytical parameters; contrast-enhanced ultrasound; enhanced permeability and retention (epr) effect; desferrioxamine mouse serum albumin zr 89; enhanced permeability and retention effect
Journal Title: Journal of Nuclear Medicine
Volume: 52
Issue: 4
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2011-04-01
Start Page: 625
End Page: 633
Language: English
DOI: 10.2967/jnumed.110.083998
PROVIDER: scopus
PUBMED: 21421727
PMCID: PMC3902086
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: JNMEA" - "Source: Scopus"
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MSK Authors
  1. Jason Philip Holland
    31 Holland
  2. Jason S Lewis
    354 Lewis
  3. Sean Denis Carlin
    83 Carlin
  4. Vadim Divilov
    16 Divilov