(212)Pb-pretargeted theranostics for pancreatic cancer Journal Article
| Authors: | Bauer, D.; Carter, L. M.; Atmane, M. I.; De Gregorio, R.; Michel, A.; Kaminsky, S.; Monette, S.; Li, M.; Schultz, M. K.; Lewis, J. S. |
| Article Title: | (212)Pb-pretargeted theranostics for pancreatic cancer |
| Abstract: | Although pancreatic ductal adenocarcinoma (PDAC) is associated with limited treatment options and poor patient outcomes, targeted a-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 a-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. © 2024 Society of Nuclear Medicine Inc.. All rights reserved. |
| Keywords: | controlled study; survival rate; cancer growth; nonhuman; pancreas cancer; radiation dose; pancreatic neoplasms; radiopharmaceuticals; mouse; animal; animals; mice; animal tissue; tumor volume; animal experiment; animal model; tumor xenograft; cell line, tumor; diagnostic imaging; disease severity; dosimetry; pancreas tumor; tumor cell line; radiopharmaceutical agent; radioisotope; radioisotopes; personalized medicine; lead; kidney tubule necrosis; pretargeting; lead 212; humans; human; female; article; precision medicine; theranostic nanomedicine; lead-203; lead-212; progeny release; targeted a-therapy |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 65 |
| Issue: | 1 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2024-01-01 |
| Start Page: | 109 |
| End Page: | 116 |
| Language: | English |
| DOI: | 10.2967/jnumed.123.266388 |
| PUBMED: | 37945380 |
| PROVIDER: | scopus |
| PMCID: | PMC10755526 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Jason Lewis -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work