Smilkov, Katarina and Gjorgieva Ackova, Darinka and Gjorgoski, Icko and Carollo, Angela and Chinol, Marco and Papi, Stefano and Signore, Alberto and Janevik-Ivanovska, Emilija (2014) Freeze-dried kit formulations for preparation of Lu-177 conjugated rituximab for treatment of non-Hodgkin’s lymphoma. In: XIII Congress of chemists and technologists of Macedonia, 8-11 Oct 2014, Ohrid, Republic of Macedonia.
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Abstract
Two radiolabelled monoclonal antibodies are approved for the treatment of non-Hodgkin’s lymphoma, Yttrium-90-ibritumomab tiuxetan, (Zevalin®) and Iodine-131-tositumomab (Bexxar®). In the current clinical practice, rituximab, a chimeric monoclonal antibody is approved for the treatment of low-grade or follicular, CD-20 positive non-Hodgkin’s lymphoma, as a single agent or in combination with chemotherapy. The radioisotope Lu-177, has a potential to be used in a radiopharmaceutical preparation as a therapy radioisotope for labelling rituximab, mainly for its advantageous characteristics, t½= 6.71 days and the ‘soft’ β emmision Eβ of 497, 384 and 172 keV with 78.6, 9.1, and 12.2% abundance, respectively) associated with γ emission with Eγ of 113 and 208 keV and 6.4 and 11% abundance, respectively), thus enabling targeted therapy and visualization studies at the same time. The aim of this work was to present the properties of the developed freeze-dried, ready-to-label kit formulations containing rituximab, conjugated with three different bifunctional chelating agents, p-SCN-Bn-DOTA, p-SCN-Bn-DTPA and 1B4M-DTPA. The radiolabelling was performed by dissolving the freeze-dried preparation with sterile saline, and subsequent labelling with 555GBq of Lutetium-177 in total volume of 1mL at pH 7.0, and incubation for 30 min at room temperature (p-SCN-Bn-DTPA-rituximab and 1B4M-DTPA-rituximab) and 60 min at 40°C (p-SCN-Bn-DOTA-rituximab). The analysis of radiochemical purity (RCP) was performed by SE-HPLC using isocratic method and immunoreactive fraction assay (IRF) using serial dilution of CD20-positive RAJI cells (0.5-8 million/ml). Mean RCP values were >95% for all three conjugates and that the immunoreactivity was 45% for 177Lu-DTPA-rituximab and 67% for 177Lu-DOTA-rituximab. These results form a basis for further evaluation of these preparations in order to select a promising new radiopharmaceutical.
| Item Type: | Conference or Workshop Item (Poster) |
|---|---|
| Subjects: | Natural sciences > Biological sciences Natural sciences > Chemical sciences Medical and Health Sciences > Health biotechnology Medical and Health Sciences > Health sciences Medical and Health Sciences > Other medical sciences |
| Divisions: | Faculty of Medical Science |
| Depositing User: | Katarina Smilkov |
| Date Deposited: | 12 Mar 2015 15:29 |
| Last Modified: | 06 Mar 2018 10:42 |
| URI: | https://eprints.ugd.edu.mk/id/eprint/11449 |
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