LNP Applications Highlight: Preclinical evaluation of cationic DOTA-triarginine-lipid conjugates for theranostic liquid brachytherapy

Posted on July 23, 2021

Lnp Applications Infographic

Brachytherapy (BT) is an internal radiation therapy that is used to treat a local, specific part of the body. This treatment uses seeds, ribbons, or capsules containing radiation and places them directly inside or near a tumor. Typically, BT is used to treat cancers of the head, neck, breast, cervix, prostate, and eye. The primary advantage of BT is the delivery of high-dose radiation directly to the tumor without affecting healthy tissues in the surrounding area. The two primary disadvantages of conventional BT is heterogenous tumor dose coverage and patient discomfort at the site of intratumoral placement.

A new method of BT involves the injection of liquids containing radioactive compounds directly into the tumor. Since the material being placed into the tumor is a liquid, a thin needle can be used to inject the radioactive treatment. The liquids are also able to spread out in the tumor and the number of injections can be reduced making this procedure less invasive and more comfortable for patients. A key area of interest for liquid BT (LBT) is finding a suitable delivery system that efficiently distributes and retains radioactive materials in the intended region. Another attractive attribute of a liquid system is the ability to map intratumoral dose distribution for better dosimetry planning. Thus, the method of LBT could be considered a theranostic since it is being used for diagnostic and therapeutic purposes. Researchers at the Technical University of Denmark and The University of Copenhagen set out to develop cationic liposomes to address both of these issues.

They developed two novel DOTA containing chelator agents with hydrophobic acyl chains and triarginine groups. They were designed to transition from cell membrane to cell membrane, while carrying the chemotherapeutic radioactive material in a controlled and gradual manner. The triarginine groups (highly positively charged) were incorporated to increase the affinity of the delivery system to cancer cells which are known to be more negatively charged than healthy cells. The developed DOTA-triarginine-lipid conjugates were proven to have a higher affinity to membranes with more negatively charged head groups. They were also labelled with 64Cu and imaged via PET/CT. Imaging showed substantial tumor retention as the free labelled conjugate and as the labelled liposome. The free labelled compound exhibited significant wash out around 6 hours after injection, but the labelled liposomal formulation showed a more stable level of intrtumoral radioactivity at 6 and 24 hours.

Many questions still need to be answered before these liposomal delivery systems could be used in humans but the potential for this type of therapy is obvious. As the research community continues to evaluate lipid delivery systems, the applications are seemingly endless. At Avanti we want to be at the forefront of lipid delivery technology and believe that we can help you in every step of your lipid delivery system research.

Check out our new LNP Technology page and see how we can aid your research!

Click HERE to read the full article on liquid brachytherapeutic applications of DOTA-triarginine-lipid conjugates.