Targeted immunoPET imaging of multiple myeloma

Current standard of care methods of imaging multiple myeloma disease burden are suboptimal. For example, fluorodeoxyglucose-(FDG)-PET/CT may fail to detect up to 50% of myeloma lesions. Immunologically based positron emission tomography (immunoPET) is an imaging modality allowing detecting of multiple myeloma by targeting specific tumor antigens using antibodies, antibody fragments, or antibody mimics labelled with position emitting radioisotopes. ImmunoPET agents for multiple myeloma have targeted CD38, CD46, CD138, BCMA, CS1, VLA-4, and CXCR4, which are all highly expressed on the majority of myeloma cells. As opposed to biopsies, immunoPET allows noninvasive, whole-body assessment of multiple myeloma tumor burden. Clinical applications of immunoPET for patients with multiple myeloma currently under investigation include disease detection, localization, quantification, biopsy targeting, and evaluation of residual disease following therapy. In addition, targeted immunoPET is under investigation for its ability to predict response to subsequent targeting therapies. For instance, immunoPET agents targeting CD38 are being used to predict response to subsequent CD38-targeted therapies using uptake on pretherapy immunoPET studies as a predictive biomarker. When the positron emitting radioisotope can be exchanged for an isotope emitting a high energy beta or alpha particle, the construct may be utilized for radioligand therapy of multiple myeloma. This review introduces the concept of immunoPET, summarizes the current immunoPET agents in development, and discusses potential clinical applications of immunoPET agents.