Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma

PRIMARY OBJECTIVE: I. To determine the sensitivity of metastatic lesion detection in multiple myeloma using zirconium Zr 89-DFO-YS5 (\[89Zr\]DFO-YS5 PET, as compared with fludeoxyglucose F-18 (18F-FDG) PET imaging. SECONDARY OBJECTIVES: I. To determine the safety of \[89Zr\]DFO-YS5. II. To determine the average organ uptake of \[89Zr\]DFO-YS5. III. To descriptively report the patterns of intra-tumoral uptake of \[89Zr\]DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal. IV. To calculate the dosimetry of \[89Zr\]DFO-YS5 in patients with multiple myeloma. EXPLORATORY OBJECTIVE: I. To determine the association between uptake (standardized uptake value maximum \[SUVmax\]) of \[89Zr\]DFO-YS5 with 1q amplification by fluorescence in situ hybridization (FISH) on tumor biopsies (when available; FISH may be conducted as part of routine, standard-of-care). OUTLINE: Participants are assigned to 1 of 2 cohorts based on participant preference. COHORT A: Participants receive \[89Zr\]DFO-YS5 intravenously (IV) and undergo a single PET/CT or PET/MRI scan 5-7 days post-injection. Participants also receive fludeoxyglucose F-18 IV and undergo PET/CT or PET/MRI scan within 28 days prior to day 1. COHORT B: Participants receive \[89Zr\]DFO-YS5 IV and undergo four PET/CT or PET/MRI scans on days 1, 2, 3-4, and 5-7 post-injection. Participants also receive fludeoxyglucose F-18 IV and undergo PET/CT or PET/MRI scan within 28 days prior to day 1. Patients are followed up at 30 days after final scan.