Macropa chelation
Macropa is a newer ring-shaped molecule built specifically to grip large radioactive metal atoms, such as the alpha-emitter actinium-225, quickly and at room temperature, which older molecules like DOTA cannot do well.
Overview
Macropa (N,N'-bis[(6-carboxy-2-pyridyl)methyl]-4,13-diaza-18-crown-6) is an 18-membered diaza-crown-6 macrocycle with two pendant picolinate arms, first reported by Thiele et al. in 2017. Unlike DOTA, whose rigid octadentate cavity favours small lanthanide-sized ions, macropa shows 'reverse size selectivity': it binds large ions (Ac3+, Pb2+, La3+, Ra2+) markedly more tightly than small ones, matching Ac3+'s large 1.12 Å ionic radius. In side-by-side testing, macropa complexed essentially all of a 26 kBq 225Ac spike within 5 minutes at room temperature at submicromolar ligand concentration, whereas DOTA complexed only around 10% under the same conditions and required 80°C to go to completion.
Bifunctional derivatives (macropa-NCS) have been conjugated to antibodies (trastuzumab, the GPC3-targeting antibody codrituzumab/GC33) and to the PSMA-targeting small molecule RPS-070, and the resulting 225Ac complexes were stable for 7-8 days against human serum and excess La3+ challenge. Rigidified analogues (H2BZmacropa, H2BZ2macropa) trade some thermodynamic stability for improved synthetic access. Macropa also complexes 212Pb, 133La, 213Bi, 223Ra and 224Ra with varying efficiency, making it one of two chelators (alongside DOTA) most discussed for 225Ac-based targeted alpha therapy as of 2026; it does not solve the separate daughter-recoil problem that follows 225Ac decay.
How it works
An 18-membered diaza-crown-6 macrocycle with two picolinate arms has a cavity sized for large metal ions, so it shows 'reverse size selectivity' and binds large ions such as Ac3+, Pb2+ and La3+ far more tightly and far faster (minutes, at room temperature) than it binds small lanthanide-sized ions, the opposite preference to DOTA.
Dependencies
Open the dependency map →Dependencies are what this technology cannot be delivered without: manufacturing steps, instruments, software, upstream methods. See its full chain on the map.
Latest papers
topQuery for this technology: (TITLE:"Macropa chelation" OR ABSTRACT:"Macropa chelation" OR TITLE:"H2macropa" OR ABSTRACT:"H2macropa" OR TITLE:"bp18c6" OR ABSTRACT:"bp18c6") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Macropa chelation, not a curated reading list.
Similar pages
not linked directly; found by shared links- TechnologySarcophagine chelation
Shares DOTA chelation, Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211) and the tags chemistry, chelator.
- TechnologyRadiohybrid (rh) chemistry
Shares DOTA chelation, Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211), Actinium-225 and the tag chemistry.
- CompanyAdvanCell
Shares Radium-224, Lead-212, Targeted alpha therapy, Actinium-225.
- IdeaFund alpha emitters beyond actinium-225: lead-212, terbium-149 and astatine-211
Shares Radium-224, Bismuth-213, Lead-212, Targeted alpha therapy.
- IdeaPretargeted alpha radioimmunotherapy
Shares Bismuth-213, Targeted alpha therapy, Actinium-225 and the tag alpha therapy.
- Key paperPhase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC
Shares Actinium-225 PSMA agents, Targeted alpha therapy, Actinium-225 and the tag alpha therapy.
- Pairing177Lu-PSMA-617 then 225Ac-PSMA rescue therapy
Shares Actinium-225 PSMA agents, Targeted alpha therapy, Actinium-225 and the tag alpha therapy.
- Key paper225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer
Shares Actinium-225 PSMA agents, Targeted alpha therapy, Actinium-225 and the tag alpha therapy.