Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer

Zheng Han; William M MacCuaig; Metin N Gurcan; Juan Claros-Sorto; Tabitha Garwe; Christina Henson; Jennifer Holter-Chakrabarty; Bethany Hannafon; Vishal Chandra; Elizabeth Wellberg; Lacey R McNally

doi:10.1016/j.pacs.2023.100531

Dynamic 2-deoxy-D-glucose-enhanced multispectral optoacoustic tomography for assessing metabolism and vascular hemodynamics of breast cancer

Photoacoustics. 2023 Jul 9:32:100531. doi: 10.1016/j.pacs.2023.100531. eCollection 2023 Aug.

Authors

Affiliations

¹ Department of Surgery, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
² Center for Health Systems Innovation, Oklahoma State University, Stillwater, OK 74078, USA.
³ Department of Bioengineering, University of Oklahoma, Norman, OK 73019, USA.
⁴ Center for Biomedical Informatics, Wake Forest Baptist Health, Winston-Salem, NC 27101, USA.
⁵ Department of Biostatistics and Epidemiology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
⁶ Department of Internal Medicine, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
⁷ Department of Obstetrics and Gynecology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
⁸ Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.

Abstract

Clinical tools for measuring tumor vascular hemodynamics, such as dynamic contrast-enhanced MRI, are clinically important to assess tumor properties. Here we explored the use of multispectral optoacoustic tomography (MSOT), which has a high spatial and temporal resolution, to measure the intratumoral pharmacokinetics of a near-infrared-dye-labeled 2-Deoxyglucose, 2-DG-800, in orthotropic 2-LMP breast tumors in mice. As uptake of 2-DG-800 is dependent on both vascular properties, and glucose transporter activity - a widely-used surrogate for metabolism, we evaluate hemodynamics of 2-DG-MP by fitting the dynamic MSOT signal of 2-DG-800 into two-compartment models including the extended Tofts model (ETM) and reference region model (RRM). We showed that dynamic 2-DG-enhanced MSOT (DGE-MSOT) is powerful in acquiring hemodynamic rate constants, including K^trans and K_ep, via systemically injecting a low dose of 2-DG-800 (0.5 µmol/kg b.w.). In our study, both ETM and RRM are efficient in deriving hemodynamic parameters in the tumor. Area-under-curve (AUC) values (which correlate to metabolism), and K^trans and K_ep values, can effectively distinguish tumor from muscle. Hemodynamic parameters also demonstrated correlations to hemoglobin, oxyhemoglobin, and blood oxygen level (SO₂) measurements by spectral unmixing of the MSOT data. Together, our study for the first time demonstrated the capability of DGE-MSOT in assessing vascular hemodynamics of tumors.

Keywords: 2-deoxyglucose; Breast cancer; Extended Tofts model; Hemodynamics; Metabolism; Multispectral optoacoustic tomography, optoacoustic imaging; Pharmacokinetics; Photoacoustic imaging; Reference region model.

Abstract

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