{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hu A"],"funding":["U.S. Department of Energy","NIBIB NIH HHS","NIGMS NIH HHS","National Science Foundation"],"pagination":["e202300457"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10939043"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(35)"],"pubmed_abstract":["To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large 132/135La3+, 213Bi3+, and small 44Sc3+. Here, we report a 10-step organic synthesis of its bifunctional analogue py-macrodipa-NCS, which contains an amine-reactive -NCS group that is amenable for bioconjugation reactions to targeting vectors. The hydrolytic stability of py-macordipa-NCS was assessed, revealing a half-life of 6.0 d in pH 9.0 aqueous buffer. This bifunctional chelator was then conjugated to a prostate-specific membrane antigen (PSMA)-binding moiety, yielding the bioconjugate py-macrodipa-PSMA, which was subsequently radiolabeled with large 132/135La3+ and small 47Sc3+, revealing efficient and quantitative complex formation. The resulting radiocomplexes were injected into mice bearing both PSMA-expressing and PSMA-non-expressing tumor xenografts to determine their biodistribution patterns, revealing delivery of both 132/135La3+ and 47Sc3+ to PSMA+ tumor sites. However, partial radiometal dissociation was observed, suggesting that py-macrodipa-PSMA needs further structural optimization."],"journal":["European journal of inorganic chemistry"],"pubmed_title":["Construction of the Bioconjugate Py-Macrodipa-PSMA and Its In Vivo Investigations with Large <sup>132/135</sup>La<sup>3+</sup> and Small <sup>47</sup>Sc<sup>3+</sup> Radiometal Ions."],"pmcid":["PMC10939043"],"funding_grant_id":["DESC0020197","CHE-1531632","T32 GM136572","R01 EB029259","R21 EB027282"],"pubmed_authors":["Boros E","Wilson JJ","Engle JW","Martin KE","Smilowicz D","Hu A","Cingoranelli SJ","Lapi SE","Aluicio-Sarduy E"],"additional_accession":[]},"is_claimable":false,"name":"Construction of the Bioconjugate Py-Macrodipa-PSMA and Its In Vivo Investigations with Large <sup>132/135</sup>La<sup>3+</sup> and Small <sup>47</sup>Sc<sup>3+</sup> Radiometal Ions.","description":"To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large 132/135La3+, 213Bi3+, and small 44Sc3+. Here, we report a 10-step organic synthesis of its bifunctional analogue py-macrodipa-NCS, which contains an amine-reactive -NCS group that is amenable for bioconjugation reactions to targeting vectors. The hydrolytic stability of py-macordipa-NCS was assessed, revealing a half-life of 6.0 d in pH 9.0 aqueous buffer. This bifunctional chelator was then conjugated to a prostate-specific membrane antigen (PSMA)-binding moiety, yielding the bioconjugate py-macrodipa-PSMA, which was subsequently radiolabeled with large 132/135La3+ and small 47Sc3+, revealing efficient and quantitative complex formation. The resulting radiocomplexes were injected into mice bearing both PSMA-expressing and PSMA-non-expressing tumor xenografts to determine their biodistribution patterns, revealing delivery of both 132/135La3+ and 47Sc3+ to PSMA+ tumor sites. However, partial radiometal dissociation was observed, suggesting that py-macrodipa-PSMA needs further structural optimization.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-04T02:32:47.025Z","creation":"2025-04-04T02:32:47.025Z"},"accession":"S-EPMC10939043","cross_references":{"pubmed":["38495596"],"doi":["10.1002/ejic.202300457"]}}