Retooling a blood-based biomarker: Phase I assessment of the high-affinity CA19-9 antibody HuMAB-5B1 for immuno-PET imaging of pancreatic cancer

Christian Lohrmann, Eileen M. O'Reilly, Joseph A. O'Donoghue, Neeta Pandit-Taskar, Jorge A. Carrasquillo, Serge K. Lyashchenko, Shutian Ruan, Rebecca Teng, Wolfgang Scholz, Paul W. Maffuid, Jason S. Lewis, Wolfgang A. Weber

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Purpose: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer. Patients and Methods: In this phase I dose-escalating study, 12 patients with CA19-9–positive metastatic malignancies were injected with MVT-2163. Within 7 days, all patients underwent a total of four whole-body PET/CT scans. A diagnostic CT scan was performed prior to injection of MVT-2163 to correlate findings on MVT-2163 PET/CT. Results: Immuno-PET with MVT-2163 was safe and visualized known primary tumors and metastases with high contrast. In addition, radiotracer uptake was not only observed in metastases known from conventional CT, but also seen in subcentimeter lymph nodes located in typical metastatic sites of pancreatic cancer, which were not abnormal on routine clinical imaging studies. A significant fraction of the patients demonstrated very high and, over time, increased uptake of MVT-2163 in tumor tissue, suggesting that HuMab-5B1 labeled with beta-emitting radioisotopes may have the potential to deliver therapeutic doses of radiation to cancer cells. Conclusions: Our study shows that the tumor antigen CA19-9 secreted to the circulation can be used for sensitive detection of primary tumors and metastatic disease by immuno-PET. This significantly broadens the number of molecular targets that can be used for PET imaging and offers new opportunities for noninvasive characterization of tumors in patients.

Original languageEnglish
Pages (from-to)7014-7023
Number of pages10
JournalClinical Cancer Research
Volume25
Issue number23
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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