Journal article
Preclinical Evaluation of a Lead Specific Chelator (PSC) Conjugated to Radiopeptides for 203Pb and 212Pb-Based Theranostics
Pharmaceutics, Vol.15(2), 414
01/26/2023
DOI: 10.3390/pharmaceutics15020414
PMCID: PMC9966725
PMID: 36839736
Abstract
203Pb and 212Pb have emerged as promising theranostic isotopes for image-guided α-particle radionuclide therapy for cancers. Here, we report a cyclen-based Pb specific chelator (PSC) that is conjugated to tyr3-octreotide via a PEG2 linker (PSC-PEG-T) targeting somatostatin receptor subtype 2 (SSTR2). PSC-PEG-T could be labeled efficiently to purified 212Pb at 25 °C and also to 212Bi at 80 °C. Efficient radiolabeling of mixed 212Pb and 212Bi in PSC-PEG-T was also observed at 80 °C. Post radiolabeling, stable Pb(II) and Bi(III) radiometal complexes in saline were observed after incubating [203Pb]Pb-PSC-PEG-T for 72 h and [212Bi]Bi-PSC-PEG-T for 5 h. Stable [212Pb]Pb-PSC-PEG-T and progeny [212Bi]Bi-PSC-PEG-T were identified after storage in saline for 24 h. In serum, stable radiometal/radiopeptide were observed after incubating [203Pb]Pb-PSC-PEG-T for 55 h and [212Pb]Pb-PSC-PEG-T for 24 h. In vivo biodistribution of [212Pb]Pb-PSC-PEG-T in tumor-free CD-1 Elite mice and athymic mice bearing AR42J xenografts revealed rapid tumor accumulation, excellent tumor retention and fast renal clearance of both 212Pb and 212Bi, with no in vivo redistribution of progeny 212Bi. Single-photon emission computed tomography (SPECT) imaging of [203Pb]Pb-PSC-PEG-T and [212Pb]Pb-PSC-PEG-T in mice also demonstrated comparable accumulation in AR42J xenografts and renal clearance, confirming the theranostic potential of the elementally identical 203Pb/212Pb radionuclide pair.
Details
- Title: Subtitle
- Preclinical Evaluation of a Lead Specific Chelator (PSC) Conjugated to Radiopeptides for 203Pb and 212Pb-Based Theranostics
- Creators
- Mengshi Li - Viewpoint Molecular Targeting (United States)Nicholas J. Baumhover - Viewpoint Molecular Targeting (United States)Dijie Liu - Viewpoint Molecular Targeting (United States)Brianna S. Cagle - Viewpoint Molecular Targeting (United States)Frédéric Boschetti - SEMATECHGuillaume Paulin - SEMATECHDongyoul Lee - Korea Military AcademyZhiming Dai - University of IowaEphraim R. Obot - Viewpoint Molecular Targeting (United States)Brenna M. Marks - Viewpoint Molecular Targeting (United States)Ibrahim Okeil - Viewpoint Molecular Targeting (United States)Edwin A. Sagastume - Viewpoint Molecular Targeting (United States)Moustafa Gabr - Weill Cornell MedicineF. Christopher Pigge - University of IowaFrances L. Johnson - Viewpoint Molecular Targeting (United States)Michael K. Schultz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Pharmaceutics, Vol.15(2), 414
- DOI
- 10.3390/pharmaceutics15020414
- PMID
- 36839736
- PMCID
- PMC9966725
- NLM abbreviation
- Pharmaceutics
- ISSN
- 1999-4923
- eISSN
- 1999-4923
- Grant note
- DOI: 10.13039/100000054, name: National Cancer Institute, award: N44CA170036; R44CA203430; name: Holden Comprehensive Cancer Center Support Grant, award: P30 CA086862
- Language
- English
- Date published
- 01/26/2023
- Academic Unit
- Radiology; Stead Family Department of Pediatrics; Radiation Oncology; Chemistry; Internal Medicine
- Record Identifier
- 9984363420602771
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