Automated cassette-based production of high specific activity [ 203/212 Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer

Abstract

A method for preparation of Pb-212 and Pb-203 labeled chelator-modified peptide-based radiopharmaceuticals for cancer imaging and radionuclide therapy has been developed and adapted for automated clinical production. Pre-concentration and isolation of radioactive Pb2+ from interfering metals in dilute hydrochloric acid was optimized using a commercially-available Pb-specific chromatography resin packed in disposable plastic columns. The pre-concentrated radioactive Pb2+ is eluted in NaOAc buffer directly to the reaction vessel containing chelator-modified peptides. Radiolabeling was found to proceed efficiently at 85°C (45min; pH 5.5). The specific activity of radiolabeled conjugates was optimized by separation of radiolabeled conjugates from unlabeled peptide via HPLC. Preservation of bioactivity was confirmed by in vivo biodistribution of Pb-203 and Pb-212 labeled peptides in melanoma-tumor-bearing mice. The approach has been found to be robustly adaptable to automation and a cassette-based fluid-handling system (Modular Lab Pharm Tracer) has been customized for clinical radiopharmaceutical production. Our findings demonstrate that the Pb-203/Pb-212 combination is a promising elementally-matched radionuclide pair for image-guided radionuclide therapy for melanoma, neuroendocrine tumors, and potentially other cancers.

Development and dosimetry of 203Pb/212Pb-labelled PSMA ligands: bringing “the lead” into PSMA-targeted alpha therapy?

“…In summary, due to the theoretically well scalable on-demand production of 203 Pb in cyclotrons and of 212 Pb from 224 Ra generators [ 37 ] and after demonstration of automated cassette-based labelling procedures suitable for clinical use [ 38 ], the 203 Pb/ 212 Pb tandem approach is a reasonable option for overcoming the current supply limitation of appropriate medical alpha emitters.…”

Evaluation of a Novel Pb-203-Labeled Lactam-Cyclized Alpha-Melanocyte-Stimulating Hormone Peptide for Melanoma Targeting

“…Tl and 205 Tl targets with 13.7-MeV deuterons through a 203 Tl (d, 2n)203 Pb reaction,32 14.5-MeV protons through a 203 Tl (p, n) 203 Pb reaction,33 and 26.5-MeV protons through a 205 Tl (p, 3n) 203 Pb reaction 34. Nonradioactive Pb and Fe are the major metallic contaminants in the 203 PbCl 2 solution produced by the 205 Tl (p, 3n) 203 Pb reaction, thus serve as competitors for 203 Pb in the radiolabeling process.…”

Präzisionsonkologie revolutioniert Nuklearmedizin mit theranostischem Ansatz

“…Neben der bildlichen Darstellung ermöglichen verschiedene Tracer auch therapeutische Ansätze, wenn sie mit entsprechenden Nukliden markiert werden. In den Laboren von Eckert & Ziegler wird bereits seit vielen Jahren mit Isotopen wie 90 Y, 177 Lu, 32 P, 228 [19,20,21,22]. Diese Kassetten sind sterile Einwegmaterialien, die direkt nach der Nutzung entsorgt werden.…”