Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster lunch

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

Date

18 Nov 2017

Session

Poster lunch

Topics

Cytotoxic Therapy;  Supportive Care and Symptom Management

Presenters

Anshu Thakur

Citation

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

Authors

A. Thakur, V. Dhote

Author affiliations

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

Resources

Abstract 957

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.

Clinical trial identification

Legal entity responsible for the study

VNS Institutional Ethical Committee

Funding

None

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.