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Poster lunch

957 - Conquering cardiotoxicity of Trastuzumab- A 99Tc radiolabelled bio-distribution study (114P)


18 Nov 2017


Poster lunch


Cytotoxic Therapy;  Supportive Care and Symptom Management


Anshu Thakur


Annals of Oncology (2017) 28 (suppl_10): x26-x34. 10.1093/annonc/mdx654


A. Thakur, V. Dhote

Author affiliations

  • New Drug Development, VNS Institute of Pharmacy, 462044 - Bhopal/IN


Abstract 957


Overexpression of human epidermal growth factor receptor 2 (HER2) is responsible for approximately 35% of breast cancer cases. A number of approaches have been designed to inhibit overexpressed HER-2 receptors. Inhibiting these overexpressed HER-2 receptors in the breast is desirable. However, this inhibition never happens in isolation. HER-2 pathway in the heart, involved in the regulation of normal cellular metabolism, growth and survival, is also inhibited which leads to serious cardiotoxicity. The research was aimed to design a delivery system for trastuzumab which can bypass the cardiotoxicity without compromising the desired therapeutic action at the breast.


PEGylated liposomes of trastuzumab were formulated by lipid layer hydration technique. To ensure the maximum entrapment, different ratios of trastuzumab and lipids were utilised. The optimised formulation with maximum entrapment was labelled with 99 m Tc. In vivo biodistribution study was performed in rats xenografted with MCF-7 breast cancer cell lines to compare the biodistribution in heart and the breast tissues.


Percent entrapment efficiency (%EE) of trastuzumab in liposomes was found to be 79.7% ± 8.2%. The labelling efficiency was almost the same up to 90 min after incubation for trastuzumab and liposomes. Less than 2% of radioactivity was dissociated after 6 hours incubation in the saline which indicates the suitability of the complex for its in vivo use. Results of biodistribution revealed that in the case of 99mTc-liposomes, the radioactivity present in the cancerous breast was greater at all timepoints compared to that in the heart


PEGylated liposomes seem to be a promising delivery system to overcome the cardiomyopathy associated with trastuzumab. Pegylated lipid system spends less time in the heart due to lymphatic drainage. And whatever time it spends in the heart, it is shielded by the lipid barrier.

Clinical trial identification

Legal entity responsible for the study

VNS Institutional Ethical Committee




All authors have declared no conflicts of interest.

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