Anti‐BCMA Immuno‐NanoPET Radiotracers for Improved Detection of Multiple Myeloma

Abstract

Current clinical imaging modalities for the sensitive and specific detection of multiple myeloma (MM) rely on nonspecific imaging contrast agents based on gadolinium chelates for magnetic resonance imaging (MRI) or for 18 F-FDG-directed and combined positron emission tomography (PET) and computed tomography (CT) scans. These tracers are not, however, able to detect minute plasma cell populations in the tumor niche, leading to false negative results. Here, a novel PET-based anti-BCMA nanoplatform labeled with 64 Cu is developed to improve the monitoring of these cells in both the spine and femur and to compare its sensitivity and specificity to more conventional immunoPET ( 64 Cu labeled anti-BCMA antibody) and passively targeted PET radiotracers ( 64 CuCl 2 and 18 F-FDG). This proof-of-concept preclinical study confirmed that by conjugating up to four times more radioisotopes per antibody with the immuno-nanoPET platform, an improvement in the sensitivity and in the specificity of PET to detect tumor cells in an orthotopic model of MM is observed when compared to the traditional immunoPET approach. It is anticipated that when combined with tumor biopsy, this immuno-nanoPET platform may improve the management of patients with MM.

First-in-Humans Evaluation of Safety and Dosimetry of64Cu-LLP2A for PET Imaging

“…[ 18 F]fluorodeoxyglucose (FDG), has been the leading nuclear medicine tracer for oncologic studies, as demonstrated by its wide availability and frequent use (1). Of note, as compared to solid tumors, in hematological malignancies, 18 F-FDG-PET/CT remains the mainstay for imaging of extramedullary infiltration, relapse and assessment of inflammatory activity in leukemia as well as in 18 F-FDG-avid lymphoma (2). There is increasing evidence of superior accuracy when nuclear imaging is synergized with liquid biopsies (3).…”

“…Anatomical and functional imaging play a forefront role in the detection of minimal residual disease, relapse and therapy response as well (10). 18 F-FDG-PET/CT works adequately in patients manifesting with 18 F-FDG-avid myeloma lesions (11). Despite its frequent use in the clinic, a known limitation of 18 F-FDG-PET in MM is the inconsistent expression of the glucose transporter, GLUT-1, and the hexokinase-2 enzyme in myeloma cells (12).…”

“…18 F-FDG-PET/CT works adequately in patients manifesting with 18 F-FDG-avid myeloma lesions (11). Despite its frequent use in the clinic, a known limitation of 18 F-FDG-PET in MM is the inconsistent expression of the glucose transporter, GLUT-1, and the hexokinase-2 enzyme in myeloma cells (12). 18 F-FDG uptake can additionally change during the course of disease progression and following therapy (12,13).…”

“…Despite its frequent use in the clinic, a known limitation of 18 F-FDG-PET in MM is the inconsistent expression of the glucose transporter, GLUT-1, and the hexokinase-2 enzyme in myeloma cells (12). 18 F-FDG uptake can additionally change during the course of disease progression and following therapy (12,13). Collectively, the tumor microenvironment in MM can significantly affect the 18 F-FDG signal specificity in the BM, leading to either an over-estimation or under-estimation of disease burden.…”

“…18 F-FDG uptake can additionally change during the course of disease progression and following therapy (12,13). Collectively, the tumor microenvironment in MM can significantly affect the 18 F-FDG signal specificity in the BM, leading to either an over-estimation or under-estimation of disease burden.…”