Detection and Treatment of Ovarian Cancer by Targeting Tumor Extracellular Hydroxyapatite: A New Paradigm
Abstract
Introduction: In this report, we are evaluating tumor extracellular hydroxyapatite (HAP), Ca10(PO4)6OH2, as an imaging biomarker of ovarian can a target for therapy. We have shown that HAP-binding radiotracers such as FDA approved 18F-NaF can be used with PET imaging and 99mTc-MDP with SPECT imaging to detect breast tumors; in this context, detection of tumor-associated HAP exhibited high specificity and a high signal-to-background ratio (SBR) as HAP is absent in normal soft tissue. In ovarian cancer, conventional imaging modalities lack clear metrics for assessing tumor burden before and after surgical debulking and for assessing tumor response to therapy. This is mainly due to lack of specificity and/or low SBR ratio from standard imaging. Additionally, we had developed a nanoparticulate sulfonated polystyrene solution (NSPS) to break-up HAP in vivo inducing a localized alkalosis status in the tumor microenvironment inhibiting tumor growth. Methods: Female C57Bl/6 mice received intraperitoneal injection of ID8 mouse ovarian tumor cells that constitutively express a luciferase reporter (ID8-luc). After four weeks, bioluminescence imaging (BLI) was used to assess tumor burden and the mice were injected with tilde11 MBq/0.1 mL of 18F-NaF and imaged 60 min later for 20min in a microPET/CT. Within 24 hours, the mice were injected with tilde37 MBq/0.1 mL of 99mTc-MDP and imaging 60min later in a NanoSPECT/CT for about 20 min. The imaging protocols were repeated weakly. When tumor burden was detected across the different modalities, the mice were treated with weekly 2 mg/kg cisplatin, 6.7 mg/kg NSPS(one time), or vehicle, PBS, weekly (controls). After several weeks of cisplatin treatment, some of the mice were taken off cisplatin and treated with PBS as a model for tumor recurrence. Regions of interest (ROIs) were drawn around the abdominal cavity and the radiotracer concentration within the ROI was deduced.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2021
- Accession Number
- AD1146192
Entities
People
- J. O. Mcintyre
- Mohammed N. Tantawy
Organizations
- Vanderbilt University Medical Center