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Preparation and preclinical evaluation of 131 I‐trastuzumab for breast cancer
Author(s) -
Kameswaran Mythili,
Gota Vikram,
Ambade Rajwardhan,
Gupta Sudeep,
Dash Ashutosh
Publication year - 2017
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3465
Subject(s) - trastuzumab , chemistry , biodistribution , in vitro , breast cancer , metastatic breast cancer , cancer , pharmacology , cancer research , medicine , biochemistry
Trastuzumab that targets the human epidermal growth factor receptor type 2 (HER2) is known to benefit patients with HER2+ metastatic breast cancer. The objective was to explore the potential of 131 I‐trastuzumab for treatment of breast cancers. Radioiodination of trastuzumab was carried out by chloramine‐T method, purified by using PD‐10 column, and characterized by size exclusion high‐performance liquid chromatography on a gel column. In vitro studies were carried out in HER2+ cells to determine the specificity of the radioimmunoconjugate. Uptake and retention of 131 I‐trastuzumab were determined by biodistribution studies in tumor‐bearing non‐obese diabetic/severe combined immunodeficiency and normal severe combined immunodeficiency mice. The radiochemical purity (RCP) of 131 I‐trastuzumab was 98 ± 0.4% with retention time of 17 minutes by high‐performance liquid chromatography. In vitro stability studies exhibited RCP of more than 90% in serum at 37°C after 120 hours of radioiodination. In vitro cell binding with 131 I‐trastuzumab in HER2+ cells showed binding of 28% to 35% which was inhibited significantly, with unlabeled trastuzumab confirming its specificity. K d value of 131 I‐trastuzumab was 0.5 nM, while its immunoreactivity was more than 80%. Uptake of more than 12% and retention were observed in the tumors up to 120 hours p.i. 131 I‐trastuzumab prepared in‐house‐exhibited RCP of more than 98%, excellent immunoreactivity, affinity to HER2+ cell lines and good tumor uptake thereby indicating its potential for further evaluation in HER2+ breast cancers.