Examination of the PET in vivo generator (134)Ce as a theranostic match for (225)Ac Journal Article
| Authors: | Bauer, D.; De Gregorio, R.; Pratt, E. C.; Bell, A.; Michel, A.; Lewis, J. S. |
| Article Title: | Examination of the PET in vivo generator (134)Ce as a theranostic match for (225)Ac |
| Abstract: | Purpose: The radionuclide pair cerium-134/lanthanum-134 (134Ce/134La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (225Ac). The unique properties of 134Ce offer perspectives for developing innovative in vivo investigations that are not possible with 225Ac. In this work, 225Ac- and 134Ce-labelled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match, 134Ce/134La has limitations to the setting of quantitative positron emission tomography imaging. Methods: The precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG8-Tz) were radiolabelled with 225Ac or 134Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The 225Ac and 134Ce-labelled mcp-PEG8-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody. Results: In vitro and in vivo studies with both 225Ac and 134Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the 134Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of 134Ce’s PET-compatible daughter 134La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing 225Ac-labelled tracers are not quantitatively represented by 134Ce PET imaging. Conclusion: When employing slow-internalizing vectors, 134Ce might not be an ideal match for 225Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of 134La. However, this same characteristic makes it possible to estimate the redistribution of 225Ac’s progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment. Graphical abstract: (Figure presented.) © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; comparative study; positron emission tomography; radiopharmaceuticals; prostate specific antigen; mouse; animal; animals; mice; animal tissue; spleen; animal experiment; animal model; in vivo study; in vitro study; cell line, tumor; cancer model; monoclonal antibodies; monoclonal antibody; prostate cancer; prostate-specific antigen; prostate specific membrane antigen; chemistry; antigens; drug distribution; drug uptake; tissue distribution; tumors; dosimetry; quantitative analysis; diagnosis; pancreas tumor; tumor cell line; urology; positron-emission tomography; ligand; radiopharmaceutical agent; in-vivo; pet imaging; tracer; radioisotope; drug half life; mammals; in-vitro; thin layer chromatography; diseases; positrons; radiochemistry; theranostics; dipeptides; tumor microenvironment; pharmacokinetic parameters; actinium; single heterocyclic rings; heterocyclic compounds, 1-ring; actinium 225; bismuth 213; cerium; chelating agent; procedures; tumor-to-background ratio; actinium-225; dipeptide; pretargeting; tetrazine derivative; radiolabeling; humans; human; male; female; article; positron emission tomography-computed tomography; positron emission tomography imaging; theranostic nanomedicine; bxpc-3 cell line; vipivotide tetraxetan; internalization (cell); psma-617; tomography imaging; progeny release; targeted alpha therapy; cerium-134; cerium 134; cerium chloride ce 134; lanthanum; lanthanum 134; macropa; vipivotide tetraxetan ac 225; vipivotide tetraxetan ce 134; actinia-225; paper chromatography |
| Journal Title: | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume: | 51 |
| Issue: | 13 |
| ISSN: | 1619-7070 |
| Publisher: | Springer |
| Date Published: | 2024-11-01 |
| Start Page: | 4015 |
| End Page: | 4025 |
| Language: | English |
| DOI: | 10.1007/s00259-024-06811-w |
| PUBMED: | 38940841 |
| PROVIDER: | scopus |
| PMCID: | PMC12121724 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding authors are Jason Lewis and David Bauer -- Source: Scopus |
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