Synthesis of 111In-p-SCN-Bn-DTPA-nimotuzumab and its preclinical evaluation in EGFR positive NSCLC animal model
| العنوان: | Synthesis of 111In-p-SCN-Bn-DTPA-nimotuzumab and its preclinical evaluation in EGFR positive NSCLC animal model |
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| المؤلفون: | Syed Qaiser Shah, Gul-e Raana |
| المصدر: | Radiochimica Acta. 109:905-913 |
| بيانات النشر: | Walter de Gruyter GmbH, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Animal model, Chemistry, Cancer research, medicine, Nimotuzumab, Physical and Theoretical Chemistry, medicine.drug |
| الوصف: | The aim of this study was to investigate labeling of nimotuzumab (h-R3) with 111In using p-SCN-Bn-DTPA as bifunctional chelate, evaluate its targeting potential against SK-LU-1, H226, H650, H661, and HCC4006 non-small cell lung carcinoma (NSCLC) cell lines and correlate epidermal growth factor receptor (EGFR) expression level with internalization kinetics, biodistribution and imaging accuracy using Balb/c mice and New Zealand White rabbit (NZWR) animal model. The amount of p-SCN-Bn-DTPA attached to h-R3 was assessed by measuring relative absorbance at 652 nm with ultraviolet (UV) spectrophotometer. High-performance liquid chromatography (HPLC) was used to determine percent radiochemical purity (%RCP) and in vitro stability using excess amount of diethylenetriamine pentaacetate (DTPA). The in vitro stability in rat serum was estimated using iTLC-SG. EGFR expression level in each tumor was assessed by chemiluminescence. In vivo uptake in different organs of Balb/c mice and non-invasive imaging potential using NZWR bearing HCC4006 tumor, was evaluated with gamma camera. UV spectroscopy has confirmed the attachment of five p-SCN-Bn-DTPA (chelate) with one antibody. The HPLC indicated 98.85 ± 0.14% (n = 3) %RCP with high yield (>96%), specific activity 3.5 ± 0.0.25 mCi per mg and 94.25 ± 0.34% in vitro stability at 37 °C in mice serum. In excess DTPA no considerable transchelation was experiential from the 111In labeled p-SCN-Bn-DTPA-h-R3 to the challenger. The EGFR expression in HCC4006 was higher amongst all with band density of 23.53 relative to 1.00 of H226. Initially internalization was lower which went up 1.05 × 104 molecules per HCC4006 cell in 48 h. The optimal concentration of h-R3 for maximum uptake was 15 μg per animal. Higher uptake in target organ was observed in animal infected with HCC4006 cells. However, in excess pure h-R3 the uptake was significantly reduced indicating tumor specificity. HCC4006 target site was undistinguishable relative to background activity in the initial phase of imaging due to poor uptake. However, within 60 h the HCC4006 tumor was quite apparent. This experiment suggests that at optimal dosage of 111In labeled h-R3 can be used for localization and identification of EGFR positive NSCLC using gamma camera. |
| تدمد: | 2193-3405 0033-8230 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::caac1723593792c8268077e4ec706def https://doi.org/10.1515/ract-2021-1054 |
| رقم الأكسشن: | edsair.doi...........caac1723593792c8268077e4ec706def |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21933405 00338230 |
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