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To support the clinical translation of these modalities, radiolabelled analogues are vital for absorption, distribution, metabolism and excretion (ADME) studies, particularly for quantitative whole\u2010body autoradiography (QWBA). Access to such radio probes is limited because established methods for the preparation of\n                    <jats:sup>3<\/jats:sup>\n                    H\u2010labelled oligonucleotides are characterised by high costs, extensive lead times, low specific activity and the generation of substantial radioactive waste. To address these limitations, we developed a biocatalytic platform for late\u2010stage\n                    <jats:sup>3<\/jats:sup>\n                    H\u2010radiolabelling of oligonucleotides using methyltransferases, reducing precursor costs and radioactive waste by orders of magnitude. We demonstrate that DNA\u2010cytosine\u20105\u2010methyltransferases can methylate oligonucleotides with high regioselectivity at a preparative scale, yielding stable\u2010 and radioisotope\u2010labelled (\n                    <jats:sup>2<\/jats:sup>\n                    H and\n                    <jats:sup>3<\/jats:sup>\n                    H) samples with an unprecedented molar activity up to 3 TBq mmol\n                    <jats:sup>\u22121<\/jats:sup>\n                    (81\u00a0Ci mmol\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). In view of the precision and efficiency of methyltransferase\u2010mediated radiolabelling, we anticipate that similar approaches will facilitate QWBA studies with other drug modalities.\n                  <\/jats:p>","DOI":"10.1002\/anie.8706793","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:03:13Z","timestamp":1785153793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Enzymatic Platform for Late\u2010Stage (Radio)isotope Labelling of Oligonucleotides With Methyltransferases"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-8158","authenticated-orcid":false,"given":"Christopher R. 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