One-Step 18F-Labeling of Carbohydrate-Conjugated Octreotate-Derivatives Containing a Silicon-Fluoride-Acceptor (SiFA): In Vitro and in Vivo Evaluation as Tumor Imaging Agents for Positron Emission Tomography (PET)
| العنوان: | One-Step 18F-Labeling of Carbohydrate-Conjugated Octreotate-Derivatives Containing a Silicon-Fluoride-Acceptor (SiFA): In Vitro and in Vivo Evaluation as Tumor Imaging Agents for Positron Emission Tomography (PET) |
|---|---|
| المؤلفون: | Ljuba Iovkova, Andrea Alke, Ralf Schirrmacher, Jean-Claude Reubi, Klaus Jurkschat, Hans-Jürgen Wester, Peter Bartenstein, Beatrice Waser, Christian Fottner, Carmen Wängler, Hans-Georg Buchholz, Björn Wängler, Sabrina Niedermoser |
| المصدر: | Bioconjugate Chemistry. 21:2289-2296 |
| بيانات النشر: | American Chemical Society (ACS), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Pharmacology, chemistry.chemical_classification, Octreotate, Organic Chemistry, Radiochemistry, Biomedical Engineering, Pharmaceutical Science, Bioengineering, Peptide, Conjugated system, Combinatorial chemistry, In vitro, chemistry.chemical_compound, chemistry, In vivo, Lipophilicity, Moiety, Biotechnology, Conjugate |
| الوصف: | The synthesis, radiolabeling, and initial evaluation of new silicon-fluoride acceptor (SiFA) derivatized octreotate derivatives is reported. So far, the main drawback of the SiFA technology for the synthesis of PET-radiotracers is the high lipophilicity of the resulting radiopharmaceutical. Consequently, we synthesized new SiFA-octreotate analogues derivatized with Fmoc-NH-PEG-COOH, Fmoc-Asn(Ac₃AcNH-β-Glc)-OH, and SiFA-aldehyde (SIFA-A). The substances could be labeled in high yields (38 ± 4%) and specific activities between 29 and 56 GBq/μmol in short synthesis times of less than 30 min (e.o.b.). The in vitro evaluation of the synthesized conjugates displayed a sst2 receptor affinity (IC₅₀ = 3.3 ± 0.3 nM) comparable to that of somatostatin-28. As a measure of lipophilicity of the conjugates, the log P(ow) was determined and found to be 0.96 for SiFA-Asn(AcNH-β-Glc)-PEG-Tyr³-octreotate and 1.23 for SiFA-Asn(AcNH-β-Glc)-Tyr³-octreotate, which is considerably lower than for SiFA-Tyr³-octreotate (log P(ow) = 1.59). The initial in vivo evaluation of [¹⁸F]SiFA-Asn(AcNH-β-Glc)-PEG-Tyr³-octreotate revealed a significant uptake of radiotracer in the tumor tissue of AR42J tumor-bearing nude mice of 7.7% ID/g tissue weight. These results show that the high lipophilicity of the SiFA moiety can be compensated by applying hydrophilic moieties. Using this approach, a tumor-affine SiFA-containing peptide could successfully be used for receptor imaging for the first time in this proof of concept study. |
| تدمد: | 1520-4812 1043-1802 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::97a403aaeb599ea8183af75d09bbd1ea https://doi.org/10.1021/bc100316c |
| رقم الأكسشن: | edsair.doi...........97a403aaeb599ea8183af75d09bbd1ea |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204812 10431802 |
|---|