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

As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often unpredictable, 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 noninvasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluorodeoxyglucose (¹⁸F-FDG) is a function of the metabolic activity of both malignant and nonmalignant cells, the 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 it with the positron-emitting radionuclide copper 64 (⁶⁴Cu; 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 than does ¹⁸F-FDG PET/CT and was even more sensitive than were bioluminescence signals. We therefore have supporting evidence for using ⁶⁴Cu-DOTA-Dara as a novel imaging agent for MM.