Evaluation of 134 Ce/ 134 La as a PET Imaging Theranostic Pair for 225 Ac α-Radiotherapeutics.

Autor:	Bobba KN; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Bidkar AP; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Meher N; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Fong C; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Wadhwa A; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Dhrona S; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Sorlin A; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Bidlingmaier S; Department of Anesthesia, University of California, San Francisco, San Francisco, California., Shuere B; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., He J; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia; robert.flavell@ucsf.edu henry.vanbrocklin@ucsf.edu., Wilson DM; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Liu B; Department of Anesthesia, University of California, San Francisco, San Francisco, California.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California; and., Seo Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., VanBrocklin HF; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California; robert.flavell@ucsf.edu henry.vanbrocklin@ucsf.edu.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California; and., Flavell RR; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California; and.; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2023 Jul; Vol. 64 (7), pp. 1076-1082. Date of Electronic Publication: 2023 May 18.
DOI:	10.2967/jnumed.122.265355
Abstrakt:	225 Ac-targeted α-radiotherapy is a promising approach to treating malignancies, including prostate cancer. However, α-emitting isotopes are difficult to image because of low administered activities and a low fraction of suitable γ-emissions. The in vivo generator 134 Ce/ 134 La has been proposed as a potential PET imaging surrogate for the therapeutic nuclides 225 Ac and 227 Th. In this report, we detail efficient radiolabeling methods using the 225 Ac-chelators DOTA and MACROPA. These methods were applied to radiolabeling of prostate cancer imaging agents, including PSMA-617 and MACROPA-PEG 4 -YS5, for evaluation of their in vivo pharmacokinetic characteristics and comparison to the corresponding 225 Ac analogs. Methods: Radiolabeling was performed by mixing DOTA/MACROPA chelates with 134 Ce/ 134 La in NH 4 OAc, pH 8.0, at room temperature, and radiochemical yields were monitored by radio-thin-layer chromatography. In vivo biodistributions of 134 Ce-DOTA/MACROPA.NH 2 complexes were assayed through dynamic small-animal PET/CT imaging and ex vivo biodistribution studies over 1 h in healthy C57BL/6 mice, compared with free 134 CeCl 3 In vivo, preclinical imaging of 134 Ce-PSMA-617 and 134 Ce-MACROPA-PEG 4 -YS5 was performed on 22Rv1 tumor-bearing male nu/nu-mice. Ex vivo biodistribution was performed for 134 Ce/ 225 Ac-MACROPA-PEG 4 -YS5 conjugates. Results: 134 Ce-MACROPA.NH 2 demonstrated near-quantitative labeling with 1:1 ligand-to-metal ratios at room temperature, whereas a 10:1 ligand-to-metal ratio and elevated temperatures were required for DOTA. Rapid urinary excretion and low liver and bone uptake were seen for 134 Ce/ 225 Ac-DOTA/MACROPA. NH 2 conjugates in comparison to free 134 CeCl 3 confirmed high in vivo stability. An interesting observation during the radiolabeling of tumor-targeting vectors PSMA-617 and MACROPA-PEG 4 -YS5-that the daughter 134 La was expelled from the chelate after the decay of parent 134 Ce-was confirmed through radio-thin-layer chromatography and reverse-phase high-performance liquid chromatography. Both conjugates, 134 Ce-PSMA-617 and 134 Ce-MACROPA-PEG 4 -YS5, displayed tumor uptake in 22Rv1 tumor-bearing mice. The ex vivo biodistribution of 134 Ce-MACROPA.NH 2 , 134 Ce-DOTA and 134 Ce-MACROPA-PEG 4 -YS5 corroborated well with the respective 225 Ac-conjugates. Conclusion: These results demonstrate the PET imaging potential for 134 Ce/ 134 La-labeled small-molecule and antibody agents. The similar 225 Ac and 134 Ce/ 134 La-chemical and pharmacokinetic characteristics suggest that the 134 Ce/ 134 La pair may act as a PET imaging surrogate for 225 Ac-based radioligand therapies. (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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