DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature
Abstract Background The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled unde...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2016-03-01
|
| Series: | EJNMMI Radiopharmacy and Chemistry |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s41181-016-0007-3 |
| _version_ | 1819206039705223168 |
|---|---|
| author | Johanna Seemann Bradley Waldron David Parker Frank Roesch |
| author_facet | Johanna Seemann Bradley Waldron David Parker Frank Roesch |
| author_sort | Johanna Seemann |
| collection | DOAJ |
| description | Abstract Background The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described. Results A BFC derived from the DATA ligand (2,2’-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe1][Tyr3]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68Ga derived via four different 68Ge/68Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2–4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68Ga-DATATOC was calculated as logP = −3.2 ± 0.3, with a HPLC retention time (t R = 10.4 min) similar to 68Ga-DOTATOC (logP = −2.9 ± 0.4, t R = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C. Conclusions The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The speed, reliability, ease, flexibility and simplicity with which 68Ga-DATATOC can be prepared makes it a very attractive alternative to current standards. |
| first_indexed | 2024-12-23T05:01:16Z |
| format | Article |
| id | doaj.art-64c928a4dabc4b8f8a32e8e44a494405 |
| institution | Directory Open Access Journal |
| issn | 2365-421X |
| language | English |
| last_indexed | 2024-12-23T05:01:16Z |
| publishDate | 2016-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj.art-64c928a4dabc4b8f8a32e8e44a4944052022-12-21T17:59:13ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2016-03-011111210.1186/s41181-016-0007-3DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperatureJohanna Seemann0Bradley Waldron1David Parker2Frank Roesch3Institute of Nuclear Chemistry, Johannes Gutenberg UniversityInstitute of Nuclear Chemistry, Johannes Gutenberg UniversityDepartment of Chemistry, Durham UniversityInstitute of Nuclear Chemistry, Johannes Gutenberg UniversityAbstract Background The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described. Results A BFC derived from the DATA ligand (2,2’-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe1][Tyr3]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68Ga derived via four different 68Ge/68Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2–4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68Ga-DATATOC was calculated as logP = −3.2 ± 0.3, with a HPLC retention time (t R = 10.4 min) similar to 68Ga-DOTATOC (logP = −2.9 ± 0.4, t R = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C. Conclusions The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The speed, reliability, ease, flexibility and simplicity with which 68Ga-DATATOC can be prepared makes it a very attractive alternative to current standards.http://link.springer.com/article/10.1186/s41181-016-0007-368GaDATATOCKit-type labelling |
| spellingShingle | Johanna Seemann Bradley Waldron David Parker Frank Roesch DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature EJNMMI Radiopharmacy and Chemistry 68Ga DATA TOC Kit-type labelling |
| title | DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature |
| title_full | DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature |
| title_fullStr | DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature |
| title_full_unstemmed | DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature |
| title_short | DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature |
| title_sort | datatoc a novel conjugate for kit type 68ga labelling of toc at ambient temperature |
| topic | 68Ga DATA TOC Kit-type labelling |
| url | http://link.springer.com/article/10.1186/s41181-016-0007-3 |
| work_keys_str_mv | AT johannaseemann datatocanovelconjugateforkittype68galabellingoftocatambienttemperature AT bradleywaldron datatocanovelconjugateforkittype68galabellingoftocatambienttemperature AT davidparker datatocanovelconjugateforkittype68galabellingoftocatambienttemperature AT frankroesch datatocanovelconjugateforkittype68galabellingoftocatambienttemperature |