212Pb-Pretargeted Theranostics for Pancreatic Cancer

David Bauer; Lukas M Carter; Mohamed I Atmane; Roberto De Gregorio; Alexa Michel; Spencer Kaminsky; Sebastien Monette; Mengshi Li; Michael K Schultz; Jason S Lewis

doi:10.2967/jnumed.123.266388

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212Pb-Pretargeted Theranostics for Pancreatic Cancer

Journal article

Open access

Peer reviewed

212Pb-Pretargeted Theranostics for Pancreatic Cancer

David Bauer, Lukas M Carter, Mohamed I Atmane, Roberto De Gregorio, Alexa Michel, Spencer Kaminsky, Sebastien Monette, Mengshi Li, Michael K Schultz and Jason S Lewis

The Journal of nuclear medicine (1978), Vol.65(1), pp.109-116

01/2024

DOI: 10.2967/jnumed.123.266388

PMCID: PMC10755526

PMID: 37945380

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Abstract

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.

Details

Title: Subtitle: 212Pb-Pretargeted Theranostics for Pancreatic Cancer
Creators: David Bauer - Memorial Sloan Kettering Cancer Center
Lukas M Carter - Memorial Sloan Kettering Cancer Center
Mohamed I Atmane
Roberto De Gregorio - Memorial Sloan Kettering Cancer Center
Alexa Michel - Memorial Sloan Kettering Cancer Center
Spencer Kaminsky - Memorial Sloan Kettering Cancer Center
Sebastien Monette - Memorial Sloan Kettering Cancer Center
Mengshi Li
Michael K Schultz
Jason S Lewis - Cornell University
Resource Type: Journal article
Publication Details: The Journal of nuclear medicine (1978), Vol.65(1), pp.109-116
DOI: 10.2967/jnumed.123.266388
PMID: 37945380
PMCID: PMC10755526
eISSN: 1535-5667
Language: English
Electronic publication date: 11/09/2023
Date published: 01/2024
Academic Unit: Radiology; Radiation Oncology
Record Identifier: 9984511954802771

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