ImmunoPET in Multiple Myeloma—What? So What? Now What?

Abstract

Despite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity and resolution of a PET camera with the specificity of a radiolabelled mAb, holds the capability to cement this new treatment paradigm for MM patients. It has the potential to non-invasively monitor the distribution of therapeutic antibodies or directly monitor biomarkers on MM cells, and to allow direct observation of potential changes over time and in response to various therapeutic interventions. Tumor response could, in the future, be anticipated more effectively to provide individualized treatment plans tailored to patients according to their unique imaging signatures. This work explores the important role played by immunotherapeutics in the management of MM, and focuses on some of the challenges for this drug class and the significant interest of companion imaging agents such as immunoPET.

Annotating CD38 Expression in Multiple Myeloma with [18F]F–Nb1053

“…Noninvasive diagnosis of MM is still a clinical challenge. It has been proposed that PET is the technique of choice for imaging MM . CD38, CD138, and B-cell maturation antigen (BCMA) are established biomarkers for MMs.…”

“…It has been proposed that PET is the technique of choice for imaging MM. 19 CD38, CD138, and Bcell maturation antigen (BCMA) are established biomarkers for MMs. We asked whether 18 F-labeled CD38-targeted VHH could diagnose MMs.…”

ImmunoPET imaging of multiple myeloma with [68Ga]Ga-NOTA-Nb1053

“…Therefore, another merit of [ 68 Ga]Ga-NOTA-Nb1053 is that there is no need to administrate unlabeled Nb1053 to saturate the extremely high spleen uptake. As a companion diagnostic tool, [ 68 Ga]Ga-NOTA-Nb1053 immunoPET may optimize CD38-targeted radioimmunotherapy [33,34]. Considering that CD38 is an alternative tumor marker for other hematological malignancies [28], it is rational to expand the application scenarios of [ 68 Ga]Ga-NOTA-Nb1053.…”

New Developments in Myeloma Treatment and Response Assessment

“…Finally, immuno-PET imaging with radiolabeled monoclonal antibodies or antibody fragments has potential for MRD assessment and optimization of personalized therapy. 64 Cu-DOTA-or 89 Zr-desferrioxamine-daratumumab might be useful (131,132), as well as anti-CD138 targeted imaging (133,134). Anti-CD38 immuno-PET could be used to identify MM patients who would benefit from daratumumab and thus predict the effectiveness of treatment.…”