A pre-targeting approach for liver radioembolisation
Radioembolisation is a local form of radiation-therapy that is increasingly used to treat primary liver tumours and metastases untreatable via surgery or chemotherapy. Currently, radioembolisation procedures are performed in two steps: 1) a scout-step which is used to identify (lung) shunting and to optimize dose using the non-therapeutic radiotracer 99m-technecium magroaggregate, and 2) therapeutic-step using rather costly microspheres containing therapeutic radio-isotopes (90-Ytrium or 166-Holmium).
The sequential steps are performed as two discrete procedures, usually separated because of logistical reasons by a period of two weeks. While the clinical benefit of this approach has been demonstrated, its high cost and the preclusion of procedure-related toxicity to healthy tissue e.g. lung remains a challenge. Even when using a scout scan, shunting occurs in 10% and results in the displacement of a fraction of the therapeutic microspheres outside of the diseased area, leading to ineffective dose distribution and serious adverse effects such as radiation pneumonitis. Therefore a cheaper therapeutic alternative that provides higher accuracy is needed.
Firstly, LUMC researchers have used supramolecular chemistry to develop a two-step pre-targeting approach which integrates the scout- and therapeutic-steps in a single procedure. As the therapeutic component specifically targets the diagnostic component, this prevents discrepancies in accumulation. Hence, the dose prediction becomes more accurate and the shunting issue is solved. Uniquely, the chemical interactions chosen favour complex formation within the liver, meaning that the technology is less prone to toxic side-effects due to lung shunting.
Secondly, the pre-targeting concept used creates flexibility in the therapeutic radioisotopes that can be used for the procedure. This means more easily produced radioisotopes can be used to help bring down the treatment cost. Further, the flexibility in the use of radioisotopes also allows for the creation of kit-based radioembolisation formulation that can be prepared in the hospital. With that the current therapeutic window of two weeks can be shortened to one of only hours.
Thirdly, the supramolecular chemistry used in this invention could also be adapted for use in chemoembolization approaches or for the subcutaneous needle-injection based delivery of a therapeutic dose to isolated lesions. Again, in both these indications the ability to verify the accuracy of the delivery process before administering the therapeutic component is key.
This technology provides a more accurate and cost effective alternative to the radioembolisation procedures currently available. The technology:
Can use a wide range of (therapeutic) radioisotopes (in addition to currently used radioisotopes), as well as chemotherapeutics, creating the potential for new markets to be explored;Improves clinical logistics by allowing one day treatments. This avoids the need for the currently used complex double procedure (scout- followed by therapeutic-procedure) spread over two weeks);Allows for kit-based radioembolisation formulations to be created and with that improves the logistics of the supply chain.
We are looking for partner(s) to license the technology for commercialization to and/or to fund research into refinement and clinical translation of the technology.
Please note, header image is purely illustrative.
Source: Philip Hogeboom, NL - Wikimedia Commons - CC 3.0 Unported (CC BY 3.0)
Luris reference numberINV-0868.0606
Priority patent application filed