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Copper-64-labeled daratumumab as a PET/CT imaging tracer for multiple myeloma

Enrico Caserta, Junie Chea, Megan Minnix, Domenico Viola, Steven Vonderfecht, Paul Yazaki, Desiree Crow, Jihane Khalife, James F. Sanchez, Joycelynne M. Palmer, Susanta Hui, Nadia Carlesso, Jonathan Keats, Young Kim, Ralf Buettner, Guido Marcucci, Steven Rosen, John Shively, David Colcher, Amrita Krishnan and Flavia Pichiorri

Key points

  • Daratumumab conjugated with copper-64 efficiently binds to CD38 on myeloma cells and was mainly detected in the bones of mice.

  • PET/CT based on 64Cu-radiolabeled daratumumab displays a higher resolution and specificity to detect myeloma compared to 18F-FDG PET/CT.

Abstract

As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often non-predictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a non-invasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluoro-deoxyglucose (18F-FDG) is a function of the metabolic activity of both malignant and non-malignant cells, results frequently lack sufficient specificity. Radiolabeled antibodies targeting MM tissue may detect disease irrespective of cell metabolism. Hence, we conjugated the clinically significant CD38-directed human antibody daratumumab (Darzalex™ [Dara]) to the DOTA chelator and labeled with the positron-emitting radionuclide Copper-64 (64Cu-DOTA-Dara). Here, we show that 64Cu-DOTA-Dara can efficiently bind CD38 on the surface of MM cells and was mainly detected in the bones associated with tumor in a MM murine model. We also show that PET/CT based on 64Cu-DOTA-Dara displays a higher resolution and specificity to detect MM cell dissemination compared to 18F-FDG PET/CT and was even more sensitive than bioluminescence signals. We therefore have supporting evidence to use 64Cu-DOTA-Dara as a novel imaging agent for MM.

  • Submitted September 20, 2017.
  • Accepted December 27, 2017.