Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT

Sangkyung Choen; Michael S Kent; F Alexandra Loucks; Jonathan A Winger; Allison L Zwingenberger

doi:10.1186/s12917-024-04061-4

Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [¹⁸F]FMISO PET/CT

BMC Vet Res. 2024 May 13;20(1):196. doi: 10.1186/s12917-024-04061-4.

Authors

Sangkyung Choen¹, Michael S Kent¹, F Alexandra Loucks², Jonathan A Winger², Allison L Zwingenberger³

Affiliations

¹ Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, 1 Shields Ave, 2112 Tupper Hall, Davis, CA, 95616, USA.
² Omniox, Inc., San Francisco, CA, USA.
³ Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, 1 Shields Ave, 2112 Tupper Hall, Davis, CA, 95616, USA. azwingen@ucdavis.edu.

Abstract

Background: Hypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [¹⁸F]Fluoromisonidazole ([¹⁸F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [¹⁸F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors.

Results: Thirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMR_max) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [¹⁸F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMR_max and HV in [¹⁸F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [¹⁸F]FMISO uptake and variable changes in TMR_max and HV.

Conclusions: [¹⁸F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMR_max and HV in [¹⁸F]FMISO PET imaging.

Keywords: Canine tumors; Computed tomography (CT); H-NOX protein; Non-invasive imaging; Oxygen carrier; Positron emission tomography (PET); Therapy resistance; Tumor hypoxia; [18F]Fluoromisonidazole ([18F]FMISO).

MeSH terms

Animals
Coordination Complexes
Dog Diseases* / diagnostic imaging
Dog Diseases* / drug therapy
Dogs
Female
Male
Misonidazole* / analogs & derivatives
Neoplasms* / diagnostic imaging
Neoplasms* / drug therapy
Neoplasms* / veterinary
Positron Emission Tomography Computed Tomography* / methods
Positron Emission Tomography Computed Tomography* / veterinary
Thiosemicarbazones / pharmacology
Thiosemicarbazones / therapeutic use
Tumor Hypoxia* / drug effects

Substances

Misonidazole
fluoromisonidazole
copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)
Thiosemicarbazones
Coordination Complexes

Abstract

MeSH terms

Substances

Grants and funding