CD38-Targeted ⁸⁹Zr-DFO-Daratumumab PET of Myeloma: Immuno-PET Impacting Clinical Care

Currently, the determination of disease burden in multiple myeloma is suboptimal. Myeloma cells may not secrete abnormal immunoglobulins or free light chains, limiting blood and urinary analysis (1). Imaging by radiography and MRI is limited, and approximately 30% of myeloma lesions are not appreciable by ¹⁸F-FDG PET (2). Bone marrow biopsies are also limited by the limited sites that can be sampled (3). Thus, better methods of detecting, localizing, and quantitating myeloma cells are needed.

Here, we report on a 76-y-old man with multiple myeloma who experienced new biochemical progression after stem cell transplantation. A masked bone marrow biopsy showed no evidence of myeloma cells. ¹⁸F-FDG PET/CT was ordered to measure tumor burden and determine whether systemic therapy was appropriate; however, no lesions were visualized by ¹⁸F-FDG PET (Fig. 1).

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FIGURE 1.

(A) ¹⁸F-FDG maximum-intensity projection of 76-y-old patient with biochemically relapsed/refractory multiple myeloma is without abnormal foci of disease. (B) In contrast, ⁸⁹Zr-DFO-daratumumab maximum-intensity projection, 7 d after tracer administration, demonstrates more than 100 abnormal foci in head, neck, chest, abdomen, pelvis, and extremities (arrows). (C–E) Sagittal ⁸⁹Zr-DFO-daratumumab PET (C), CT (D), and ⁸⁹Zr-DFO-daratumumab PET/CT (E) demonstrate abnormal foci corresponding to osseous structures, representing non–¹⁸F-FDG–avid osseous myeloma lesions.

He was accrued into a phase II trial (NCT04814615) of CD38-targeted immuno-PET with ⁸⁹Zr-deferoxamine (DFO)-daratumumab. CD38 is a transmembrane glycoprotein that is expressed on virtually all myeloma cells, as well as at lower levels on normal lymphoid and myeloid cells (4). ⁸⁹Zr-DFO-daratumumab comprises the CD38-targeting antibody daratumumab, chelated through DFO to the positron-emitting radiometal ⁸⁹Zr, whose half-life of 78.4 h allows for imaging up to at least 9 d after administration (5). As antibodies such as daratumumab may take 6–7 d to optimally biodistribute onto tumor, the long half-life of ⁸⁹Zr allows optimal timing of imaging. ⁸⁹Zr-DFO-daratumumab was able to demonstrate widespread foci of disease, with subsequent image-guided biopsy providing proof of myeloma. The identification, localization, and quantification of disease led to initiation of systemic therapy with daratumumab, lenalidomide, and dexamethasone. This case suggests that ⁸⁹Zr-DFO-daratumumab immuno-PET has the potential to have an important clinical impact on patients diagnosed with multiple myeloma.

• © 2025 by the Society of Nuclear Medicine and Molecular Imaging.

• Received for publication December 18, 2024.
• Accepted for publication January 6, 2025.