{"entity":{"id":"th-227","kind":"isotope","name":"Thorium-227","aka":["227Th","Th-227"],"tldr":"A radioactive metal that, once it decays, keeps generating more damaging radioactive particles inside the tumour for weeks. Because it lasts longer than most similar treatments, it can be attached to slow-moving carriers such as full-sized antibodies.","summary":"Thorium-227 is an alpha emitter with an 18.7-day half-life -- long enough, unlike most alpha emitters, to be conjugated to slow-clearing targeting molecules such as full antibodies rather than only fast peptides. It decays through a five-alpha cascade (via 223Ra, 219Rn, 215Po, 211Pb, 211Bi, 211Po) to stable 207Tl/207Pb, releasing a total of about 32.4 MeV of alpha energy and roughly 0.96 MeV of beta energy per decay chain, making it an in vivo generator of its own daughter, radium-223.\n\nIt is chelated using octadentate 3,2-hydroxypyridinone (3,2-HOPO) ligands rather than the DOTA-family macrocycles used for most other alpha and beta emitters, and has been developed by Bayer as 'targeted thorium conjugates' (TTCs), including antibody-based constructs such as BAY 2315497 (anti-PSMA) and BAY2701439 (anti-HER2), both tested in early-phase trials.\n\n227Th is obtained from the same generator/supply chain as radium-223: it is the immediate alpha-decay daughter of actinium-227 (itself made by neutron irradiation of radium-226 in a reactor, 226Ra(n,γ)227Ra → β− → 227Ac), separated from the growing 227Ac/227Th/223Ra generator column. Because production piggybacks on the well-established 223Ra supply chain (ORNL, PNNL, Rosatom, Bayer), 227Th is considered available at the research and early-clinical scale, though its co-produced daughter 223Ra must be removed and accounted for as a radioactive impurity in any 227Th-labelled drug product.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Targeted thorium-227 conjugates as treatment options in oncology (Front Med, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9885765/"},{"label":"Production and supply of alpha particle emitting radionuclides for TAT (JNM, 2021)","url":"https://jnm.snmjournals.org/content/jnumed/early/2021/07/22/jnumed.120.261016.full.pdf"},{"label":"Development of radiopharmaceuticals for targeted alpha therapy (PMC, 2022)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9812962/"}],"tags":["therapy","alpha emitter","antibody-compatible","in vivo generator"],"related":["ra-223","targeted-alpha-therapy","her2","psma"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"227Th","element":"Thorium","massNumber":227,"halfLife":"18.7 days","emissions":["α cascade (via 223Ra, 219Rn, 215Po, 211Pb, 211Bi, 211Po) to stable 207Pb: total ~32.4 MeV α, ~0.96 MeV β per chain","γ 236 keV (11.2%) and 50 keV (8.5%)"],"emissionClass":"alpha","use":"therapy","tissueRange":"Tens of micrometres (alpha range), delivered progressively as the daughter chain decays","production":"Generator: harvested from a reactor-derived 227Ac source (226Ra(n,γ)227Ra → β− → 227Ac), from which 227Th is separated on an ongoing basis.","supply":"emerging","supplyNote":"Piggybacks on the 223Ra/227Ac supply chain (ORNL, PNNL, Rosatom, Bayer, and in Europe the Institute for Energy Technology in Norway distributed via Bayer, or JRC Karlsruhe for the PRISMAP consortium); available at research and early-clinical scale but not yet at large commercial scale.","chelators":["3,2-HOPO (octadentate hydroxypyridinone)"],"pairedWith":["zr-89"]},"route":"/isotopes/th-227/","neighbours":{"isotope":[{"id":"ra-223","kind":"isotope","name":"Radium-223","route":"/isotopes/ra-223/"}],"technology":[{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"mesothelin","kind":"target","name":"Mesothelin (MSLN)","route":"/targets/mesothelin/"},{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}]}}