Precise Detection of Multiple Myeloma Using 18F-Labeled Anti- B-cell Maturation Antigen Nanobody

Authors

• B Ghaemi
• CP Olkowski
• F Basuli
• J Shi
• E Hill
• O Jcobson
• PL Choyke

Abstract

Introduction: B-cell maturation antigen (BCMA), highly expressed on malignant plasma cells in multiple myeloma (MM), is an ideal target for diagnostics and therapy. While 18F-FDG is commonly used for detection of MM in patients, its lack of sensitivity and specificity fails to provide information that can guide treatment. Moreover, 18F-FDG is not effective in identifying small plasma cell populations within the tumor microenvironment, which can lead to false-negative results. Our project aimed to develop a BCMA-specific tracer for MM detection. We selected nanobodies due to their small size (15 kDa), high specificity, rapid clearance, and deep tissue penetration, which make them promising imaging agents.
Method: A novel anti-BCMA nanobody was labeled with 18F by conjugating the lysine residues with an 18F-fluoropyridine prosthetic group. It was then evaluated both in vitro and in vivo using two humanized multiple myeloma models (Luciferase-H929 and Luciferase-RPMI8226). The localization of these cells to the bone marrow was monitored by bioluminescence (BLI).
Results: The BCMA-targeting nanobody demonstrated high affinity to the target protein (Kd = 6nM) and more than 70% internalization rate. In vivo PET studies with 18F-nanobody at 1h post-injection showed rapid renal clearance and high accumulation in bone marrow of MM models, aligning with BLI findings. Co-injection with excess unlabeled nanobody reduced bone marrow uptake by >90%, confirming the tracer's high specificity.
Conclusion: The results indicate that targeting BCMA overexpressed MM tumors with 18F-labeled anti-BCMA nanobody holds significant potential for theranostic applications and clinical translation.

Scientific Focus Area: Molecular Pharmacology

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