Immunotherapy of cancer Poster lunch Poster Display session

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

Presentation Number
114P
Presentation Topic
Immunotherapy of cancer
Lecture Time
13:00 - 13:00
Speakers
  • A. Thakur
Authors
  • A. Thakur
  • V. Dhote
Session Title
Session Room
Exhibition area, Singapore, Singapore, Singapore
Date
18.11.2017
Session Time
13:00 - 14:00

Abstract

Background

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.

Methods

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.

Results

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

Conclusions

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.

Legal entity responsible for the study

VNS Institutional Ethical Committee

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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