Abstract 4472: Self-assembly of CD38-binding peptides into nanofibers for imaging multiple myeloma

Abstract CD38 is overexpressed in multiple myeloma (MM) and the target of clinically approved therapeutic antibodies daratumumab and isatuximab. Our lab has previously developed a peptide-based radiotracer (LS1209) that targets CD38 for specific and sensitive imaging in MM. In this study, we demonstrate that the addition of lipid tails to LS1209 templates self-assembly of this peptide into multivalent nanofibers with morphology controlled by the length of the lipid tail. Morphology of the nanofibers was assessed via conventional and cryo-electron microscopy. Internal packing of the peptides was assessed via fluorescence. As the length of the lipid tail increases, the average spacing between residues increases. Additionally, there is a distinct morphologic change between cylindrical nanofibers and helical nanofibers as the lipid tail increases in length from a hexanoic acid tail to an octanoic acid tail. These nanofibers effectively multimerize LS1209 in order to take advantage of multivalent and cooperative binding to CD38, which was assessed via surface plasmon resonance (SPR) and cell surface binding. We demonstrate that binding activity is related to nanofiber morphology and the packing density/availability of peptides for binding interactions. Additionally, the nanofiber design co-localizes radiotracers to the site of interest without CD38 binding events, leading to additional increases in signal. The nanofibers demonstrate high efficiency radiolabeling with 64Cu and are stable at 24h in serum when assessed by radio thin layer chromatography. Preliminary animal experiments demonstrate no toxicity at expected imaging and high concentration (20x) doses. Citation Format: Jacqueline Godbe, Amit Kumar Sharma, Rui Tang, Han Jing, Alexander Zheleznyak, Monica Shokeen. Self-assembly of CD38-binding peptides into nanofibers for imaging multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4472.