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| Home > Publications database > 73/75Se-Labeling by preparation of Se-N-bonded 1,2,5-selendiazoles |
| Home > Publications database > 73/75Se-Labeling by preparation of Se-N-bonded 1,2,5-selendiazoles |
| Contribution to a conference proceedings/Journal Article | FZJ-2026-03765 |
; ;
2025
Elsevier Science
Amsterdam [u.a.]
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Please use a persistent id in citations: doi:10.1016/j.nucmedbio.2025.109266
Abstract: Introduction: Se-73 is an underutilized radionuclide for positron emission tomography (PET) with favorable chemical and physical properties. Its advantageous decay characteristics − high positron intensity, moderate positron energy, absence of high-energy photons and an intermediate half-life of 7.2 hours − make it an ideal alternative to commonly applied radiometals. Furthermore, selenium’s ability to form stable covalent bonds with elements like carbon and nitrogen enables robust incorporation into radiotracers, while the long-lived isotope Se-75 (T1/2 = 119 d) serves as a convenient surrogate for Se-73 during radiochemical method development. However, the complexity of current multi-step radiolabeling strategies has hindered the development of selenium-based radiotracers, with only a few reaching (pre)clinicalapplications. Building on our previous work on the selective formation of 75/73Se‑labeled selendiazoles for isolation of selenium isotopes from irradiated arsenic targets [1], we now report a novel late-stage radioselenation method based on aromatic diamines as selenium binding motif. Methods: Se-75 was produced via the 75As(p,n)75Se nuclear reaction by bombarding monoisotopic arsenic (As2O3) with 17 MeV protons. The irradiated target was dissolved in 2 M NaOH and the resulting solution was adjusted to different pH values with HCl before it was directly applied for radiolabeling. Initial optimization of the reaction conditions (pH, temperature and reaction time) was performed using 2,3-diaminobenzoic acid as a model compound and its pentafluorophenol ester as acylation reagent for indirect radioselenation (Fig. 1). Conjugation of the radiolabeled active ester to amines was evaluated using the peptidomimetic PSMA-binding motif Glu-C(O)-Lys. Additionally, direct radioselenation of an unprotected Glu-C(O)-Lys-based precursor functionalized with a selenium-binding motif was investigated as a proof of concept for late-stage labeling of small-molecules and peptides. Results: Radiolabeling of 2,3-diaminobenzoic acid in acetonitrile/water at 80 °C was nearly complete within 10 min and afforded radiochemical conversions (RCCs) of 40% at pH 7 and 66% at pH 2. Radioselenation of the active ester yielded similar RCCs of 60% at pH 2 but no product at pH ≥4. Reactions performed at 20, 60, or 100 °C resulted in RCCs of 32%, 51%, and 70%, respectively. After isolation by RP-SPE, the 75Se-labeled active ester was obtained with radiochemical purities of N98%. Subsequent conjugation to Glu-C(O)-Lys in ethanol and 0.2 M Et4NHCO3 proceeded with RCCs of 70-90% within 10 min at room temperature. Direct labeling of the diamine-functionalized precursor at pH 2 without organic co-solventafforded RCCs of 65-75% within 10 min at 80 °C. Conclusions: Aromatic diamines as selenium-binding motif offer a versatile and efficient platform for late-stage radioselenation, addressing the current limitations of 73Se as PET radionuclide. The high-yielding, rapid, and straightforward protocol developed here could pave the way for broader application of this unique radionuclide, significantly expanding its potential for preclinical and clinical PET imaging.
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