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 KrishnanFlavia Pichiorri

Research output: Contribution to journalArticle

21 Scopus citations

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 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 ofMMcells 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 detectMMcell 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.

Original languageEnglish (US)
Pages (from-to)741-745
Number of pages5
JournalBlood
Volume131
Issue number7
DOIs
StatePublished - Feb 15 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Caserta, E., Chea, J., Minnix, M., Viola, D., Vonderfecht, S., Yazaki, P., Crow, D., Khalife, J., Sanchez, J. F., Palmer, J. M., Hui, S., Carlesso, N., Keats, J., Kim, Y., Buettner, R., Marcucci, G., Rosen, S., Shively, J., Colcher, D., ... Pichiorri, F. (2018). Copper 64-labeled daratumumab as a PET/CT imaging tracer for multiple myeloma. Blood, 131(7), 741-745. https://doi.org/10.1182/blood-2017-09-807263