Speaker
Summary
Introduction
Nanobody-based PET tracers have emerged as highly specific tools for imaging defined immune cell subsets with rapid tissue penetration and fast blood clearance. Short-lived positron emitters as 18F are well-suited due for such rapid pharmacokinetics but can limit coordinated multi-center workflows. We therefore explored 64Cu as a radionuclide platform for nanobody imaging targeting immune cells in the context of viral infection.
Description of the Work or Project
We selected a previously validated SIRPα-specific nanobody targeting pan-myeloid cells and optimized its design for site-specific coupling of the chelator NODAGA. 64Cu was produced via 64Ni(p,n)64Cu on a medical cyclotron with trace-metal-clean purification to achieve radiolabeling at high molar activity.
Radiolabeling was performed under mild conditions with full quality control, including biological assays. The 12.7 h half-life of 64Cu enabled post-labeling stability testing and controlled inter-laboratory shipment of the ready-to-inject tracer from Tübingen to BPRC (Rijswijk, NL), where non-human primate (cynomolgus macaque) PET/CT imaging was conducted on clinical scanner platforms.
In vivo, SIRPα-directed PET revealed the spatiotemporal distribution and recruitment dynamics of myeloid cells, whereas TSPO-PET reflected macrophage activation states. These complementary signals illustrate distinct biological dimensions: SIRPα maps total myeloid cell presence and redistribution, while TSPO highlights metabolically active, tissue-remodeling macrophage populations.
Conclusions
64Cu provides strategic advantages for nanobody-based PET beyond biological half-life matching, particularly for multi-site translational workflows. As distributed imaging pipelines and cross-institutional validation become increasingly important, this strategy supports both methodological rigor and practical feasibility of collaborative PET imaging.
References
Stammes, M. A., Koopman, G., Wagner, T. R., Traenkle, B., Kaiser, P. D., Mooij, P., van der Werff, N., Acar, R. F., Böszörményi, K. P., Blaess, S., Pezzana, S., Reischl, G., Maurer, A., Langermans, J. A. M., Rothbauer, U., Kneilling, M., & Sonanini, D. (2025). Noninvasive monitoring of inflammatory processes by myeloid cell-directed PET tracers in an experimental severe acute respiratory syndrome coronavirus 2 infection model. Journal of Nuclear Medicine. Advance online publication. https://doi.org/10.2967/jnumed.125.269721
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