Tracking Pharmacodynamics of Vascular Targeted Therapy with Photoacoustic Imaging.

Abstract

HomeRadiology: Imaging CancerVol. 2, No. 1 PreviousNext Research HighlightsFree AccessTracking Pharmacodynamics of Vascular Targeted Therapy with Photoacoustic ImagingGary D. LukerGary D. LukerGary D. LukerPublished Online:Jan 31 2020https://doi.org/10.1148/rycan.2020204004MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: To investigate feasibility of noninvasive photoacoustic imaging for quantifying pharmacodynamics of vascular-targeted therapy in tumors.■ Key Result: Photoacoustic imaging measured time- and dose-dependent effects of an investigation of a vascular disrupting agent in two preclinical models of cancer.■ Impact: Photoacoustic imaging can successfully monitor pharmacodynamics of tumor vasculature during therapy, supporting applications in drug development and clinical translation for precision medicine.Imaging methods to analyze pharmacodynamics, the activity of a compound on its therapeutic target, potentially will increase development of new drugs for cancer and enable precision therapy for patients. Vascular disrupting agents represent a new class of anticancer compounds designed to target immature blood vessels typically associated with tumors. Success of these agents remains limited by a viable peripheral rim of cancer cells perfused by adjacent normal blood vessels and intertumor differences in susceptibility to hypoxia. Photoacoustic imaging, which uses low-intensity, nonionizing laser pulses to generate ultrasound waves for an image, provides an excellent method to image tumor blood vessels based on sensitive, high-contrast detection of hemoglobin. Using a high-resolution photoacoustic imaging instrument, Johnson et al measured the effects of the vascular disrupting agent OXi4503 in two different mouse models of colon cancer. In both models, photoacoustic imaging revealed initial ablation of internal blood vessels and subsequent regrowth of tumor vasculature over 16 days of treatment. For well-perfused tumors with extensive immature blood vessels, reductions in tumor blood vessels correlated highly with reductions in tumor volume over time. While poorly perfused tumors with larger, more mature blood vessels showed modest reductions in tumor blood vessels, changes in tumor vasculature did not predict effects on tumor volume. Treatment failures in poorly perfused tumors mirror past studies demonstrating resistance of such tumors to vascular disrupting therapy. Photoacoustic imaging also measured dose-dependent reductions in tumor blood vessels, establishing an approach to optimize doses and dosing schedules. These results establish photoacoustic imaging as a preclinical imaging method to advance development of vascular-targeted therapies. Furthermore, since photoacoustic instruments have entered clinical testing, this research supports future clinical applications of photoacoustic methods for pharmacodynamic imaging.Highlighted ArticleJohnson SP, Ogunlade O, Lythgoe MF, Beard P, Pedley RB. Longitudinal photacoustic imaging of the pharmacodynamics effect of vascular targeted therapy on tumors. Clin Cancer Res 2019;25:7436–7447. doi: 10.1158/1078-0432.CCR-19-036Highlighted ArticleJohnson SP, Ogunlade O, Lythgoe MF, Beard P, Pedley RB. Longitudinal photacoustic imaging of the pharmacodynamics effect of vascular targeted therapy on tumors. Clin Cancer Res 2019;25:7436–7447. doi: 10.1158/1078-0432.CCR-19-036 Crossref, Medline, Google ScholarArticle HistoryPublished online: Jan 31 2020 FiguresReferencesRelatedDetailsRecommended Articles Irreversible Electroporation versus Radiofrequency Ablation: A Comparison of Local and Systemic Effects in a Small-Animal ModelRadiology2016Volume: 280Issue: 2pp. 413-424Midterm Safety and Efficacy of Irreversible Electroporation of Malignant Liver Tumors Located Close to Major Portal or Hepatic VeinsRadiology2017Volume: 285Issue: 3pp. 1023-1031Local-Regional Treatment of Hepatocellular Carcinoma: A Primer for RadiologistsRadioGraphics2022Volume: 42Issue: 6pp. 1670-1689Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal TherapyRadiology2016Volume: 281Issue: 1pp. 109-118Animal Models of Hepatocellular Carcinoma for Local-Regional Intraarterial TherapiesRadiology: Imaging Cancer2022Volume: 4Issue: 4See More RSNA Education Exhibits Novel Image-Guided Micro-Invasive Percutaneous Treatments of Breast Lesions: Where Do We Stand?Digital Posters2019Imaging Features at the Periphery – Hemodynamics, Pathophysiology and Impact on LI-RADS CategorizationDigital Posters2020A Practical Guide of Locoregional Treatment for Patients with Hepatocellular CarcinomaDigital Posters2019 RSNA Case Collection Adult colo-colonic intussusceptionRSNA Case Collection2020Cerebral Cavernous Venous MalformationRSNA Case Collection2021Pseudocirrhosis of Hepatic Breast MetastasesRSNA Case Collection2020 Vol. 2, No. 1 Metrics Altmetric Score PDF download