RT Journal Article SR Electronic T1 212Pb-Pretargeted Theranostics for Pancreatic Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.123.266388 DO 10.2967/jnumed.123.266388 A1 Bauer, David A1 Carter, Lukas M. A1 Atmane, Mohamed I. A1 De Gregorio, Roberto A1 Michel, Alexa A1 Kaminsky, Spencer A1 Monette, Sebastien A1 Li, Mengshi A1 Schultz, Michael K. A1 Lewis, Jason S. YR 2023 UL http://jnm.snmjournals.org/content/early/2023/11/09/jnumed.123.266388.abstract AB Although pancreatic ductal adenocarcinoma (PDAC) is associated with limited treatment options and poor patient outcomes, targeted α-particle therapy (TAT) represents a promising development in the field. TAT shows potential in treating metastatic cancers, including those that have become resistant to conventional treatments. Among the most auspicious radionuclides stands the in vivo α-generator 212Pb. Combined with the imaging-compatible radionuclide 203Pb, this theranostic match is a promising modality rapidly translating into the clinic. Methods: Using the pretargeting approach between a radiolabeled 1,2,4,5-tetrazine (Tz) tracer and a trans-cyclooctene (TCO) modified antibody, imaging and therapy with radiolead were performed on a PDAC tumor xenograft mouse model. For therapy, 3 cohorts received a single administration of 1.1, 2.2, or 3.7 MBq of the pretargeting agent, [212Pb]Pb-DO3A-PEG7-Tz, whereby administered activity levels were guided by dosimetric analysis. Results: The treated mice were holistically evaluated; minimal-to-mild renal tubular necrosis was observed. At the same time, median survival doubled for the highest-dose cohort (10.7 wk) compared with the control cohort (5.1 wk). Conclusion: This foundational study demonstrated the feasibility and safety of pretargeted TAT with 212Pb in PDAC while considering dose limitations and potential adverse effects.