[89Zr]ZrDFO-CR011 PET Correlates with Response to Glycoprotein Nonmetastatic Melanoma B–targeted Therapy in Triple-negative Breast Cancer

Supum Lee, Alessandra Cavaliere, Jean Dominique Gallezot, Tibor Keler, Sharon K. Michelhaugh, Erika Belitzky, Michael Liu, Tim Mulnix, Stephen E. Maher, Alfred L.M. Bothwell, Fangyong Li, Manali Phadke, Sandeep Mittal, Bernadette Marquez-Nostra

Research output: Contribution to journalArticlepeer-review

Abstract

There is a need for prognostic markers to select patients most likely to benefit from antibody–drug conjugate (ADC) therapy. We quantified the relationship between pretreatment PET imaging of glycoprotein nonmetastatic melanoma B (gpNMB) with 89Zr-labeled anti-gpNMB antibody ([89Zr]ZrDFO-CR011) and response to ADC therapy (CDX-011) in triple-negative breast cancer. First, we compared different PET imaging metrics and found that standardized uptake values (SUV) and tumor-to-heart SUV ratios were sufficient to delineate differences in radiotracer uptake in the tumor of four different cell- and patient-derived tumor models and achieved high standardized effect sizes. These tumor models with varying levels of gpNMB expression were imaged with [89Zr]ZrDFO-CR011 followed by treatment with a single bolus injection of CDX-011. The percent change in tumor volume relative to baseline (% CTV) was then correlated with SUVmean of [89Zr]ZrDFO-CR011 uptake in the tumor. All gpNMB-positive tumor models responded to CDX-011 over 6 weeks of treatment, except one patient-derived tumor regrew after 4 weeks of treatment. As expected, the gpNMB-negative tumor increased in volume by 130 59% at endpoint. The magnitude of pretreatment SUV had the strongest inverse correlation with the % CTV at 2–4 weeks after treatment with CDX-011 (Spearman r = -0.8). However, pretreatment PET imaging with [89Zr]ZrDFO-CR011 did not inform on which tumor types will regrow over time. Other methods will be needed to predict resistance to treatment.

Original languageEnglish (US)
Pages (from-to)440-447
Number of pages8
JournalMolecular Cancer Therapeutics
Volume21
Issue number3
DOIs
StatePublished - Mar 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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