Evaluation of a Novel Macromolecular Cascade-Polymer Contrast Medium for Dynamic Contrast-Enhanced MRI Monitoring of Antiangiogenic Bevacizumab Therapy in a Human Melanoma Model

Autor: Bundit Chaopathomkul, V Rogut, David M. Shames, Clemens C. Cyran, Michael F. Wendland, Robert C. Brasch, Yanjun Fu
Rok vydání: 2013
Předmět:
human melanoma xenograft
Pathology
anti-angiogenesis effect
Nude
Dynamic MRI
Contrast Media
Angiogenesis Inhibitors
Polyethylene Glycols
chemistry.chemical_compound
Heterocyclic Compounds
Monoclonal
Humanized
Melanoma
Cancer
Tumor
Neovascularization
Pathologic
medicine.diagnostic_test
Chemistry
Magnetic Resonance Imaging
Bevacizumab
Nuclear Medicine & Medical Imaging
Treatment Outcome
Dynamic contrast-enhanced MRI
Biomedical Imaging
Drug Monitoring
medicine.drug
Macromolecule
medicine.medical_specialty
Macromolecular Substances
Clinical Sciences
Bioengineering
Antineoplastic Agents
Capsules
Polyethylene glycol
bevacizumab
Antibodies
Monoclonal
Humanized
Sensitivity and Specificity
Antibodies
Article
Cell Line
Rats
Nude
Clinical Research
Cell Line
Tumor
PEG ratio
Organometallic Compounds
medicine
Animals
Humans
Radiology
Nuclear Medicine and imaging
Neovascularization
Pathologic
business.industry
gadolinium polyethylene glycol polymer contrast agent
Reproducibility of Results
Magnetic resonance imaging
medicine.disease
Rats
Contrast medium
Nuclear medicine
business
Zdroj: Academic radiology, vol 20, iss 10
ISSN: 1076-6332
DOI: 10.1016/j.acra.2013.07.010
Popis: Rationale and objectivesTo assess the applicability of a novel macromolecular polyethylene glycol (PEG)-core gadolinium contrast agent for monitoring early antiangiogenic effects of bevacizumab using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI).Materials and methodsAthymic rats (n = 26) implanted with subcutaneous human melanoma xenografts underwent DCE-MRI at 2.0 T using two different macromolecular contrast agents. The PEG core cascade polymer PEG12,000-Gen4-(Gd-DOTA)16, designed for clinical development, was compared to the prototype, animal-only, macromolecular contrast medium (MMCM) albumin-(Gd-DTPA)35. The treatment (n = 13) and control (n = 13) group was imaged at baseline and 24 hours after a single dose of bevacizumab (1 mg) or saline to quantitatively assess the endothelial-surface permeability constant (K(PS), μL⋅min⋅100 cm(3)) and the fractional plasma volume (fPV,%), using a two-compartment kinetic model.ResultsMean K(PS) values, assessed with PEG12,000-Gen4-(Gd-DOTA)16, declined significantly (P < .05) from 29.5 ± 10 μL⋅min⋅100 cm(3) to 10.4 ± 7.8 μL⋅min⋅100 cm(3) by 24 hours after a single dose of bevacizumab. In parallel, K(PS) values quantified using the prototype MMCM albumin-(Gd-DTPA)35 showed an analogous, significant decline (P < .05) in the therapy group. No significant effects were detected on tumor vascularity or on microcirculatory parameters in the control group between the baseline and the follow-up scan at 24 hours.ConclusionDCE-MRI enhanced with the novel MMCM PEG12,000-Gen4-(Gd-DOTA)16 was able to monitor the effects of bevacizumab on melanoma xenografts within 24 hours of a single application, validated by the prototype, animal-only albumin-(Gd-DTPA)35. PEG12,000-Gen4-(Gd-DOTA)16 may be a promising candidate for further clinical development as a macromolecular blood pool contrast MRI agent.
Databáze: OpenAIRE
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