Evaluation of 177Lu and 47Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry
- PMID: 34714082
- DOI: 10.1021/acs.molpharmaceut.1c00711
Evaluation of 177Lu and 47Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry
Abstract
Lu-177-based, targeted radiotherapeutics/endoradiotherapies are an emerging clinical tool for the management of various cancers. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) remains the workhorse for such applications but can limit apparent molar activity or efficient charge modulation, which can impact target binding and, as a consequence, target efficacy. Previously, our lab had developed the small, rare earth selective bifunctional chelator, picaga, as an efficient bifunctional chelator for scandium and lutetium isotopes. Here, we assess the performance of these constructs for therapy in prostate-specific membrane antigen (PSMA)-expressing tumor xenografts. To assess the viability of picaga conjugates in conjunction with long in vivo circulation, a picaga conjugate functionalized with a serum albumin binding moiety, 177Lu-picaga-Alb53-PSMA, was also synthesized. A directly comparative, low, single 3.7 MBq dose treatment study with Lu-PSMA-617 was conducted. Treatment with 177Lu-picaga-Alb53-PSMA resulted in tumor regression and lengthened median survival (54 days) when compared with the vehicle (16 days), 47Sc-picaga-DUPA-, 177Lu-picaga-DUPA-, and 177Lu-PSMA-617-treated cohorts (21, 23, and 21 days, respectively).
Keywords: Lu-177; PSMA; Sc-47; dosimetry; endoradiotherapy; serum albumin binding.
Similar articles
-
Preparation of 177Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.Biomed Res Int. 2021 Nov 20;2021:1555712. doi: 10.1155/2021/1555712. eCollection 2021. Biomed Res Int. 2021. PMID: 34845436 Free PMC article.
-
A Walk with Lu-177 PSMA: How Close we Have Reached from Bench to Bedside?Cancer Invest. 2020 Sep;38(8-9):486-492. doi: 10.1080/07357907.2020.1811301. Epub 2020 Sep 14. Cancer Invest. 2020. PMID: 32804008 Review.
-
Enhancing Treatment Efficacy of 177Lu-PSMA-617 with the Conjugation of an Albumin-Binding Motif: Preclinical Dosimetry and Endoradiotherapy Studies.Mol Pharm. 2018 Nov 5;15(11):5183-5191. doi: 10.1021/acs.molpharmaceut.8b00720. Epub 2018 Oct 5. Mol Pharm. 2018. PMID: 30251544
-
Single Low-Dose Injection of Evans Blue Modified PSMA-617 Radioligand Therapy Eliminates Prostate-Specific Membrane Antigen Positive Tumors.Bioconjug Chem. 2018 Sep 19;29(9):3213-3221. doi: 10.1021/acs.bioconjchem.8b00556. Epub 2018 Aug 22. Bioconjug Chem. 2018. PMID: 30105912
-
[PSMA-targeted radioligand therapy in prostate cancer].Urologe A. 2017 Jan;56(1):32-39. doi: 10.1007/s00120-016-0274-3. Urologe A. 2017. PMID: 27885457 Review. German.
Cited by
-
Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [177Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.Korean J Radiol. 2024 Feb;25(2):179-188. doi: 10.3348/kjr.2023.0656. Korean J Radiol. 2024. PMID: 38288897 Free PMC article. Clinical Trial.
-
Radiochemical and Biological Evaluation of 3p-C-NETA-ePSMA-16, a Promising PSMA-Targeting Agent for Radiotheranostics.Pharmaceuticals (Basel). 2023 Jun 15;16(6):882. doi: 10.3390/ph16060882. Pharmaceuticals (Basel). 2023. PMID: 37375829 Free PMC article.
-
Radiolabeling and in vivo evaluation of lanmodulin with biomedically relevant lanthanide isotopes.RSC Chem Biol. 2023 Apr 13;4(6):414-421. doi: 10.1039/d3cb00020f. eCollection 2023 Jun 7. RSC Chem Biol. 2023. PMID: 37292057 Free PMC article.
-
Advances in PSMA theranostics.Transl Oncol. 2022 Aug;22:101450. doi: 10.1016/j.tranon.2022.101450. Epub 2022 May 18. Transl Oncol. 2022. PMID: 35597190 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous