Comparative Study of Subcutaneous and Orthotopic Mouse Models of Prostate Cancer: Vascular Perfusion, Vasculature Density, Hypoxic Burden and BB2r-Targeting Efficacy

Scientific Reports
Wenting ZhangJered C Garrison

Abstract

The gastrin-releasing peptide receptor (BB2r) is overexpressed in a variety of cancers including prostate cancer. As a consequence, the development of BB2r-targeted diagnostic/therapeutic radiopharmaceuticals has been widely explored. Both subcutaneous and orthotopic mouse models have been extensively used in BB2r-targeted agent development, but side-by-side studies examining how biological parameters (tumor perfusion efficacy, hypoxic burden and microvasculature density) impact BB2r-targeted agent delivery has not been reported. Herein, we examine these biological parameters using subcutaneous and orthotopic PC-3 xenografts. Using a dual isotope biodistribution study, tumor perfusion was accessed using [99mTc]NaTcO4 and BB2r-targeted uptake evaluated by utilization of a novel 177Lu-labeled conjugate ([177Lu]Lu-DOTA-SP714). Immunofluorescence, immunohistochemistry and autoradiography were utilized to examine the tumor vascular density, hypoxic burden and microdistribution of the BB2r-targeted agent. Our studies demonstrated that compared to the subcutaneous model the PC-3 orthotopic tumors had significantly higher levels of perfusion that led to higher BB2r-targeted uptake and lower levels of hypoxia burden. It is anticipated t...Continue Reading

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Citations

May 5, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Kavita MallyaManeesh Jain
Sep 4, 2021·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·Jenny Ling-Yu ChenMing-Jium Shieh

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Methods Mentioned

BETA
xenografts
xenograft
confocal microscopy
dissection

Software Mentioned

GraphPad PRISM
ZEN
IVIS ® Spectrum

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