*3.8. 89Zr-Daratumumab*

The membrane glycoprotein cluster of differentiation 38 (CD38) is expressed at a high density by almost all myeloma cells, and at relatively low levels on normal hematopoietic cells. CD38 is an established therapeutic target in MM. Daratumumab is an FDA-approved therapeutic monoclonal antibody that binds directly to CD38, offering a clinical benefit in MM patients [89–91]. Recently, daratumumab was radiolabeled with 89Zr through deferoxamine (DFO), producing the PET agent 89Zr-DFO-daratumumab. The results of a Phase I first-in-human 89Zr-DFO-daratumumab PET/CT imaging study in six MM patients demonstrated successful whole-body PET visualization of MM with focal tracer uptake in previously known as well as unknown sites of osseous myeloma, consistent with successful CD38-targeted immunoPET imaging of myeloma in human patients [92]. Although these results warrant validation in further prospective studies, they are highly promising for the usage of this PET antibody in diagnosis and staging of MM. Moreover, it could be applied in terms of a personalized, daratumumab-directed imaging in order to identify those MM patients who would benefit from daratumumab and thus predict the effectiveness of therapy in the context of a thera(g)nostic approach in MM.

#### **4. Conclusions**

PET/CT with 18F-FDG is increasingly gaining acceptance in the management of MM patients, and is considered a powerful diagnostic tool for the detection of medullary and extramedullary disease at initial diagnosis, a reliable predictor of survival, as well as the most robust modality for treatment response evaluation in the disease. On the other hand, 18F-FDG carries the limitations of a rather poor sensitivity for the detection of diffuse bone marrow infiltration, a relatively low specificity, and the lack of widely applied, established criteria for image interpretation. These drawbacks have led to the development of several alternative PET tracers for MM detection. Some of these radiotracers have provided promising results—such as 18F-choline and 11C-choline, 11C-acetate, 11C-methionine, 68Ga-pentixafor and 89Zr-Daratumumab—but most studies were performed in small patient cohorts and require validation in further prospective clinical trials.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
