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

Abstract

Noninvasive diagnosis of multiple myeloma (MM) is a clinical challenge. CD38 is an established biomarker for MM, and the development of CD38-targeted radiotracers may improve the management of MM. By taking the advantages of bioorthogonal click chemistry, a nanobody (i.e., Nb1053-LLQS) specific for CD38 was successfully labeled with 18F. The diagnostic efficacy and specificity of the developed tracer (i.e., [18F]­F–Nb1053) were evaluated by immuno-positron emission tomography (immunoPET) imaging in disseminated MM.1S-bearing models. [18F]­F–Nb1053 was developed with high radiochemical purity (>98%) and excellent immunoreactivity. [18F]­F–Nb1053 immunoPET successfully delineated disseminated MM lesions in preclinical MM models. The uptake in the humerus, femur, and tibia was 1.42 ± 0.50%ID/g, 1.35 ± 0.53%ID/g, and 1.48 ± 0.67%ID/g (n = 6), respectively. Tumor uptake of [18F]­F–Nb1053 decreased after daratumumab premedication, indicating the superior specificity of the reported probe. This work successfully developed a novel CD38-specific probe [18F]­F–Nb1053 that may potentially optimize the management of MM upon clinical translation.

99mTc-CD3813: A Nanobody-Based Single Photon Emission Computed Tomography Radiotracer with Clinical Potential for Myeloma Imaging and Evaluation of CD38 Expression

“…68 Ga-NOTA-Nb1053 and 18 F-Nb1053 also showed the capability in visualizing MM and lymphoma in preclinical imaging studies with PET/CT. , Since Nb1053 competes with DARA in binding to CD38, it is not appropriate to use 68 Ga-NOTA-Nb1053 and 18 F-Nb1053 to visualize CD38-positive tumors or evaluate the CD38 expression levels and MM burden, while DARA remains inside the body due to its much longer biological half-life than that of nanobody CD3813. In this respect, 99m Tc-CD3813 offers distinctive advantages over 68 Ga-NOTA-Nb1053 and 18 F–Nb1053 in visualizing the CD38-positive tumors, evaluating the MM burden, and noninvasively monitoring the therapeutic efficacy of the DARA treatment.…”

“…Nanobodies have irreplaceable advantages over the full-sized antibodies for in vivo imaging and targeted delivery due to their much faster clearance kinetics from background organs . Most CD38-targeted molecular imaging probes bind to the epitopes overlapping with the binding site of DARA, − implying that noninvasive imaging of the CD38 expression would be interfered with if DARA is not completely eliminated from the MM patient.…”

Development and comparison of 68Ga/18F/64Cu-labeled nanobody tracers probing Claudin18.2

“…The 18 F-labeling precursor (denoted as RJDJ01) was synthesized following prior publications. 20 , 32 [ 18 F]F-RJDJ01 was synthesized in an automatic module. Briefly, 39.9 GBq of 18 F-fluoride was produced and eluted with potassium carbonate (3 mg) and 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (15 mg) in 1.4 mL of acetonitrile.…”

“…In recent work, we designed nanobody-based CD38-targeted probes [ 68 Ga]Ga-NOTA-Nb1053/[ 18 F]F-Nb1053 and further reported the excellent diagnostic potencies in multiple myeloma models. 19 , 20 We also developed [ 68 Ga]Ga-NOTA-SNA006 to noninvasively map human CD8 + T cells. 21 Nanobody-based probes are favored for clinical translation and routine applications in our view.…”

Single-Domain Antibody Theranostics on the Horizon

“…CD38 (12,24,25), B-cell maturation antigen (26), CS1 (27,28), and paraprotein (29) are promising targets exploited for molecular imaging of multiple myeloma. 68 Ga-NOTA-Nb1053 is the firstgeneration CD38-specific sdAb tracer that realized precise delineation of disseminated multiple myeloma in preclinical settings (Fig.…”