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

不同表型肿瘤中通透性和滞留效应增强的程度:89Zr-白蛋白作为模型系统

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作者:Carola Heneweer #, Jason P Holland #, Vadim Divilov, Sean Carlin, Jason S Lewis

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.

Methods

These preliminary studies use (89)Zr-labeled mouse serum albumin ((89)Zr-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 (89)Zr-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.

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