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 that our results will allow researchers to better understand the biological variables affecting drug delivery and assist them in more clearly interpreting their results in this common prostate cancer mouse model.
| Original language | English (US) |
|---|---|
| Number of pages | 1 |
| Journal | Scientific reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 31 2019 |
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ASJC Scopus subject areas
- General
Cite this
Comparative Study of Subcutaneous and Orthotopic Mouse Models of Prostate Cancer : Vascular Perfusion, Vasculature Density, Hypoxic Burden and BB2r-Targeting Efficacy. / Zhang, Wenting; Fan, Wei; Rachagani, Satyanarayana; Zhou, Zhengyuan; Lele, Subodh M.; Batra, Surinder K.; Garrison, Jered C.
In: Scientific reports, Vol. 9, No. 1, 31.07.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparative Study of Subcutaneous and Orthotopic Mouse Models of Prostate Cancer
T2 - Vascular Perfusion, Vasculature Density, Hypoxic Burden and BB2r-Targeting Efficacy
AU - Zhang, Wenting
AU - Fan, Wei
AU - Rachagani, Satyanarayana
AU - Zhou, Zhengyuan
AU - Lele, Subodh M.
AU - Batra, Surinder K.
AU - Garrison, Jered C.
PY - 2019/7/31
Y1 - 2019/7/31
N2 - 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 that our results will allow researchers to better understand the biological variables affecting drug delivery and assist them in more clearly interpreting their results in this common prostate cancer mouse model.
AB - 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 that our results will allow researchers to better understand the biological variables affecting drug delivery and assist them in more clearly interpreting their results in this common prostate cancer mouse model.
UR - http://www.scopus.com/inward/record.url?scp=85070890582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070890582&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-47308-z
DO - 10.1038/s41598-019-47308-z
M3 - Article
C2 - 31366895
AN - SCOPUS:85070890582
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
ER -