{"entity":{"id":"sarcophagine-chelation","kind":"technology","name":"Sarcophagine chelation","aka":["Sar","cage amine chelator","MeCOSar"],"tldr":"Sarcophagine is a cage-shaped molecule that locks copper atoms inside so tightly that the copper cannot escape once the imaging or treatment dose is made, even inside the body.","summary":"Sarcophagine ('sar', 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) is a hexaazamacrobicyclic cage-amine ligand, developed originally by Sargeson and colleagues, whose fully encapsulating three-dimensional cage confers exceptional kinetic inertness on its copper(II) complexes. Because the copper ion is enclosed rather than merely chelated at a macrocycle rim, sarcophagine complexes form rapidly (typically 5-20 minutes) at room temperature across a broad pH range (4-9) and resist demetalation and reduction to Cu+ far more effectively than open-chain or single-ring chelators such as DTPA or NOTA. The bifunctional derivative MeCOSar (methyl-carboxylate sarcophagine) is the most widely used variant for peptide and antibody conjugation.\n\nSarcophagine chelation is the basis of the clinical 64Cu/67Cu-SARTATE and 64Cu/67Cu-SAR-bisPSMA agents and of numerous 64Cu-labelled antibody constructs (including sarcophagine-trastuzumab and sarcophagine-cetuximab conjugates for PET imaging), where head-to-head comparisons have shown less than 6% loss of 64Cu from sarcophagine-antibody conjugates in serum over 48 hours, matching or beating NOTA. A drawback of first-generation sarcophagines (SarAr) is that the residual positive charge on the copper-cage complex increases kidney retention of labelled antibody fragments; charge-modified analogues (AmBaSar, and dibromomaleimide-linked variants) reduce this off-target renal uptake while retaining the fast, room-temperature labelling that makes sarcophagines attractive for 64Cu (and increasingly 67Cu) theranostic pairs.","asOf":"2026-09-22","links":[{"label":"Development of multi-functional chelators based on sarcophagine for 64Cu chelation (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6270798/"},{"label":"Comparison of bifunctional chelators including sarcophagine for 64Cu-rituximab labelling (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4756438/"},{"label":"Potential theranostics of breast cancer with copper-64/67-sarcophagine-trastuzumab (Chem. Sci. 2025)","url":"https://pubs.rsc.org/en/content/articlehtml/2025/sc/d4sc06969b"},{"label":"IAEA: Copper-64 radiopharmaceuticals - production, quality control and clinical applications","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/PUB1961_web.pdf"}],"tags":["chemistry","chelator","copper-64"],"related":["dota-chelation","radioimmunotherapy","pretargeted-radioimmunotherapy","cu-64","cu-67"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["cyclotron-isotope-production"],"notes":[],"principle":"A three-dimensional hexaazamacrobicyclic cage fully encloses a copper ion on all sides, rather than gripping it at a ring rim, so the metal cannot demetalate or be reduced away in vivo; the closed cage also lets complexation happen in minutes at room temperature across a wide pH range.","strengths":[],"limitations":[],"since":"1980s (cage-amine ligand chemistry by Sargeson); bifunctional MeCOSar-NHS for bioconjugation from mid-2000s"},"route":"/technologies/sarcophagine-chelation/","neighbours":{"technology":[{"id":"cyclotron-isotope-production","kind":"technology","name":"Cyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211)","route":"/technologies/cyclotron-isotope-production/"},{"id":"dota-chelation","kind":"technology","name":"DOTA chelation","route":"/technologies/dota-chelation/"},{"id":"pretargeted-radioimmunotherapy","kind":"technology","name":"Pretargeted radioimmunotherapy","route":"/technologies/pretargeted-radioimmunotherapy/"},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"}],"isotope":[{"id":"cu-64","kind":"isotope","name":"Copper-64","route":"/isotopes/cu-64/"},{"id":"cu-67","kind":"isotope","name":"Copper-67","route":"/isotopes/cu-67/"}]}}