دورية أكاديمية
Comparison of (64)Cu-complexing bifunctional chelators for radioimmunoconjugation:labeling efficiency, specific activity, and in vitro/in vivo stability
| العنوان: | Comparison of (64)Cu-complexing bifunctional chelators for radioimmunoconjugation:labeling efficiency, specific activity, and in vitro/in vivo stability |
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| المؤلفون: | Cooper, Maggie S., Ma, Michelle, Sunassee, Kavitha, Shaw, Karen P., Williams, Jennifer D., Paul, Rowena L., Donnelly, Paul S., Blower, Philip J. |
| المصدر: | Cooper , M S , Ma , M , Sunassee , K , Shaw , K P , Williams , J D , Paul , R L , Donnelly , P S & Blower , P J 2012 , ' Comparison of (64)Cu-complexing bifunctional chelators for radioimmunoconjugation : labeling efficiency, specific activity, and in vitro/in vivo stability ' , Bioconjugate Chemistry , vol. 23 , no. 5 , pp. 1029-1039 . https://doi.org/10.1021/bc300037wTest |
| سنة النشر: | 2012 |
| المجموعة: | King's College, London: Research Portal |
| مصطلحات موضوعية: | Animals, Antibodies, Monoclonal, Murine-Derived, Chelating Agents, Copper Radioisotopes, Drug Stability, Female, Immunoconjugates, Isotope Labeling, Macrocyclic Compounds, Mice, Inbred BALB C, Positron-Emission Tomography, Radiopharmaceuticals, Rituximab, Tissue Distribution |
| الوصف: | High radiolabeling efficiency, preferably to high specific activity, and good stability of the radioimmunoconjugate are essential features for a successful immunoconjugate for imaging or therapy. In this study, the radiolabeling efficiency, in vitro stability, and biodistribution of immunoconjugates with eight different bifunctional chelators labeled with (64)Cu were compared. The anti-CD20 antibody, rituximab, was conjugated to four macrocyclic bifunctional chelators (p-SCN-Bn-DOTA, p-SCN-Bn-Oxo-DO3A, p-SCN-NOTA, and p-SCN-PCTA), three DTPA derivatives (p-SCN-Bn-DTPA, p-SCN-CHX-A″-DTPA, and ITC-2B3M-DTPA), and a macrobicyclic hexamine (sarcophagine) chelator (sar-CO2H) = (1-NH2-8-NHCO(CH2)3CO2H)sar where sar = sarcophagine = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane). Radiolabeling efficiency under various conditions, in vitro stability in serum at 37 °C, and in vivo biodistribution and imaging in normal mice over 48 h were studied. All chelators except sar-CO2H were conjugated to rituximab by thiourea bond formation with an average of 4.9 ± 0.9 chelators per antibody molecule. Sar-CO2H was conjugated to rituximab by amide bond formation with 0.5 chelators per antibody molecule. Efficiencies of (64)Cu radiolabeling were dependent on the concentration of immunoconjugate. Notably, the (64)Cu-NOTA-rituximab conjugate demonstrated the highest radiochemical yield (95%) under very dilute conditions (31 nM NOTA-rituximab conjugate). Similarly, sar-CO-rituximab, containing 1/10th the number of chelators per antibody compared to that of other conjugates, retained high labeling efficiency (98%) at an antibody concentration of 250 nM. In contrast to the radioimmunoconjugates containing DTPA derivatives, which demonstrated poor serum stability, all macrocyclic radioimmunoconjugates were very stable in serum with <6% dissociation of (64)Cu over 48 h. In vivo biodistribution profiles in normal female Balb/C mice were similar for all the macrocyclic radioimmunoconjugates with most of the activity remaining in the blood ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1021/bc300037w |
| الإتاحة: | https://doi.org/10.1021/bc300037wTest https://kclpure.kcl.ac.uk/portal/en/publications/comparison-of-64cucomplexing-bifunctional-chelators-for-radioimmunoconjugationTest(3ccadc13-ee2b-4537-a748-ec90951cf7f5).html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756438Test/ |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1EA10D63 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/bc300037w |
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