The Use of Animal Models in the Assessment of Tumour Vascular Disrupting Agents (VDAs)

Pedley, R. Barbara; Tozer, Gillian M.

doi:10.1007/978-1-4419-6609-4_3

Cited by 2 publications

(2 citation statements)

References 93 publications

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“…A third possible reason is the efflux of vascular and cellular debris including absorbing hemoglobin fragments from the destroyed tumor core being pushed to the periphery of the tumor due to interstitial pressure (46). This necrotic debris has previously been observed by transmission electron microscopy at 24 hours after treatment with OXi4503 (47).…”

Section: Discussionmentioning

confidence: 92%

Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors

Johnson

Ogunlade

Lythgoe

et al. 2019

Clinical Cancer Research

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Purpose: Photoacoustic imaging (PAI) is a novel noninvasive and nonionizing imaging technique that allows longitudinal imaging of tumor vasculature in vivo and monitoring of response to therapy, especially for vascular targeted chemotherapy agents. In this study, we used a novel high-resolution all-optical PAI scanner to observe the pharmacodynamic response to the vascular-disrupting agent OXi4503.Experimental Design: Two models of colorectal carcinoma (SW1222 and LS174T) that possess differing pathophysiologic vascularization were established as subcutaneous tumors in mice. Monitoring of response was performed over a 16-day "regrowth" period following treatment at 40 mg/kg, and at day 2 for a "dose response" study at 40 mg/kg, 10 mg/kg, 1 mg/kg, and sham dose.Results: Qualitative and quantitative changes in PA signal are observed, with an initial decrease followed by a plateau and subsequent return of signal indicating regrowth. Both tumor types exhibited a decrease in signal; however, the more vascularized SW1222 tumors show greater response to treatment. Decreasing the dose of OXi4503 led to a decrease in PA signal intensity of 60%, 52%, and 20% in SW1222 tumors and 30%, 26%, and 4% for LS174T tumors.Conclusions: We have shown for the first time that PAI can observe the pharmacodynamic response of tumor vasculature to drug treatment both longitudinally and at different dose levels. Assessment of differing response to treatment based on vascular pathophysiologic differences among patients has the potential to provide personalized drug therapy; we have demonstrated that PAI, which is clinically translatable, could be a powerful tool for this purpose.

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Section: Discussionmentioning

confidence: 92%

Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors

Johnson

Ogunlade

Lythgoe

et al. 2019

Clinical Cancer Research

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“…We and others have demonstrated that vascular disrupting agents (VDAs), a class of drug that specifically destroys established tumor vasculature, causes central necrosis but spares the periphery [9,[20][21][22][23][24][25][26]. We, therefore, hypothesized that combining RIT with VDAs would increase efficacy by targeting physiologically distinct tumor regions (FiguRe 3).…”

Section: Research Spotlight | News and Analysismentioning

confidence: 97%

Research Spotlight - Radioimmunotherapy: Optimizing Delivery to Solid Tumors

Rajkumar

Dearling

Packard

et al. 2011

Therapeutic Delivery

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Radioimmunotherapy (RIT) is a cancer treatment that exploits the specific targeting capability of monoclonal antibodies to deliver cytotoxic radionuclides to antigen-expressing tumor cells or stromal targets. While this has been extremely successful in the treatment of hematologic malignancies, RIT of solid tumors has produced less prolonged effects. In our laboratory, we have developed a bench-to-bedside translational pipeline with the aim of optimizing RIT for solid tumors. We will show how preclinical models of colorectal adenocarcinoma were initially used to study reciprocal interactions between elements of the tumor microenvironment and RIT and to test novel therapeutic strategies. These studies were then used to facilitate the design of novel trials carried out in close collaboration with our clinical colleagues.

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The Use of Animal Models in the Assessment of Tumour Vascular Disrupting Agents (VDAs)

Cited by 2 publications

References 93 publications

Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors

Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors

Research Spotlight - Radioimmunotherapy: Optimizing Delivery to Solid Tumors

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