DOI: 10.1186/s13550-018-0380-xPages: 1-11

Treatment response assessment with (R)-[11CPAQ PET in the MMTV-PyMT mouse model of breast cancer

1. Karolinska Institutet, Department of Clinical Neuroscience

2. Karolinska Institutet, Department of Oncology-Pathology

3. Karolinska Institutet, Department of Cell and Molecular Biology

4. Karolinska Institutet, Department of Women’s and Children’s Health

5. Karolinska University Hospital, Department of Neuroradiology, Karolinska Experimental Research and Imaging Center

6. Karolinska University Hospital, Department of Comparative Medicine, Karolinska Experimental Research and Imaging Center

7. Karolinska Institutet, Core Facility for Morphologic Phenotype Analysis, Laboratory Medicine

Correspondence to:
T. Tegnebratt
Email: tetyana.tegnebratt@ki.se

Close

Abstract

Background

The goal of the study was to assess the potential of the vascular endothelial growth factor receptor (VEGFR)-2-targeting carbon-11 labeled (R)-N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methoxy)-4-quinazolineamine ((R)-[11C]PAQ) as a positron emission tomography (PET) imaging biomarker for evaluation of the efficacy of anticancer drugs in preclinical models.

Methods

MMTV-PyMT mice were treated with vehicle alone (VEH), murine anti-VEGFA antibody (B20-4.1.1), and paclitaxel (PTX) in combination or as single agents. The treatment response was measured with (R)-[11C]PAQ PET as standardized uptake value (SUV)mean, SUVmax relative changes at the baseline (day 0) and follow-up (day 4) time points, and magnetic resonance imaging (MRI)-derived PyMT mammary tumor volume (TV) changes. Expression of Ki67, VEGFR-2, and CD31 in tumor tissue was determined by immunohistochemistry (IHC). Non-parametric statistical tests were used to evaluate the relation between (R)-[11C]PAQ radiotracer uptake and therapy response biomarkers.

Results

The (R)-[11C]PAQ SUVmax in tumors was significantly reduced after 4 days in the B20-4.1.1/PTX combinational and B20-4.1.1 monotherapy groups (p < 0.0005 and p < 0.003, respectively). No significant change was observed in the PTX monotherapy group. There was a significant difference in the SUVmax change between the VEH group and B20-4.1.1/PTX combinational group, as well as between the VEH group and the B20-4.1.1 monotherapy group (p < 0.05). MRI revealed significant decreases in TV in the B20-4.1.1/PTX treatment group (p < 0.005) but not the other therapy groups. A positive trend was observed between the (R)-[11C]PAQ SUVmax change and TV reduction in the B20-4.1.1/PTX group. Statistical testing showed a significant difference in the blood vessel density between the B20-4.1.1/PTX combinational group and the VEH group (p < 0.05) but no significant difference in the Ki67 positive signal between treatment groups.

Conclusions

The results of this study are promising. However, additional studies are necessary before (R)-[11C]PAQ can be approved as a predictive radiotracer for cancer therapy response.

This article is freely available, click here to access the full text/PDF

  • Accepted: Mar 23, 2018
  • Online: Apr 3, 2018

Article Tools

eanm
EJNMMI Ad