Noninvasive Assessment of Losartan-Induced Increase in Functional Microvasculature and Drug Delivery in Pancreatic Ductal Adenocarcinoma
| Autor: | Yves Boucher, Vidhya Kumar, Alexander R. Guimaraes, Hao Liu, Andrew J. Hoover, Rakesh K. Jain, Jacob M. Hooker, Ciprian Catana, Diego dos Santos Ferreira, Tobias Ritter |
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| Rok vydání: | 2016 |
| Předmět: |
Cancer Research
Angiotensin receptor medicine.medical_specialty medicine.medical_treatment Urology Blood volume lcsh:RC254-282 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Pancreatic cancer medicine Saline medicine.diagnostic_test business.industry Magnetic resonance imaging lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 3. Good health Surgery Ferumoxytol Losartan Oncology 030220 oncology & carcinogenesis business Perfusion medicine.drug |
| Zdroj: | Translational Oncology, Vol 9, Iss 5, Pp 431-437 (2016) |
| ISSN: | 1936-5233 |
| Popis: | PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC) models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI) of magnetic iron oxide nanoparticles (MNPs) and micro–positron emission tomography (PET) measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan. METHOD AND MATERIALS: All experiments were approved by the local Institutional Animal Care and Use Committee. FVB mice with orthotopic PDAC were treated daily with an i.p. injection of losartan (70 mg/kg) or saline (control vehicle) for 5 days. In order to calculate the fractional blood volume, vessel size index, and vessel density index, MRI was performed at 4.7 T following the injection of 3 mg/kg iron ferumoxytol (i.v.). Dynamic PET images were also acquired for 60 minutes using an 18F-5FU tracer dose of 200 μCi and analyzed for time activity curves normalized to muscle. Statistical analyses compared both cohorts using an unpaired two-tailed t test. RESULTS: In comparison to the control treatment, the losartan administration significantly increased the fractional blood volume (mean ± SEM) [12.1 ± 1.7 (n = 19) vs 6.7 ± 1.1 (n = 20); P |
| Databáze: | OpenAIRE |
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