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A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

ABSTRACT: Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.

SUBMITTER: Scheepbouwer C

PROVIDER: S-EPMC4988778 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

Scheepbouwer Chantal C Meyer Sandra S Burggraaf Maroeska J MJ Jose Jithin J Molthoff Carla F M CF

PloS one 20160817 8

Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of i ...[more]

PMID: 27533303

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Project description:PurposeTo demonstrate in an orthotopic xenograft brain tumor model that a functionalized metallofullerene (f-Gd₃N@C₈₀) can enable longitudinal tumor imaging and, when radiolabeled with lutetium 177 (¹⁷⁷Lu) and tetraazacyclododecane tetraacetic acid (DOTA) (¹⁷⁷Lu-DOTA-f-Gd₃N@C₈₀), provide an anchor to deliver effective brachytherapy.Materials and methodsAll experiments involving the use of mice were carried out in accordance with protocols approved by the institutional animal care and use committee. Human glioblastoma U87MG cells were implanted by using stereotactic procedures into the brains of 37 female athymic nude-Foxn1nu mice and allowed to develop into a tumor for 8 days. T1- and T2-weighted magnetic resonance (MR) imaging was performed in five mice. Biodistribution studies were performed in 12 mice at four time points over 7 days to evaluate gadolinium content. Survival studies involved 20 mice that received infusion of a nanoplatform by means of convection-enhanced delivery (CED) 8 days after tumor implantation. Mice in survival studies were divided into two groups: one comprised untreated mice that received f-Gd₃N@CC₈₀ alone and the other comprised mice treated with brachytherapy that received 1.11 MBq of ¹⁷⁷Lu-DOTA-f-Gd₃N@CC₈₀. Survival data were evaluated by using Kaplan-Meier statistical methods.ResultsMR imaging showed extended tumor retention (25.6% ± 1.2 of the infused dose at 52 days, confirmed with biodistribution studies) of the f-Gd₃N@CC₈₀ nanoplatform, which enabled longitudinal imaging. Successful coupling of ¹⁷⁷Lu to the f-Gd₃N@CC₈₀ surface was achieved by using a bifunctional macrocyclic chelator. The extended tumor retention allowed for effective brachytherapy, as indicated by extended survival time (> 2.5 times that of the untreated group) and histologic signs of radiation-induced tumor damage.ConclusionThe authors have developed a multimodal nanoplatform and have demonstrated longitudinal tumor imaging, prolonged intratumoral probe retention, biodistribution, and extended survival in an orthotopic xenograft brain tumor model.

Dataset Information

A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

Publications

A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

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