The problem #
Computerized tomography (CT) scans with a contrast agent in the small intestine are made for two different purposes. The first is to make the small intestine clearly visible on the images, so it can be identified when looking for lesions in other organs. The second purpose is to depict lesions in the small intestine itself – processes that most often originate from the mucosa, that forms the interface to the small intestine´s interior.
Existing contrast agents can only achieve a low contrast between the intestine´s wall and interior, a limitation that hampers the diagnostic work-up with CT. For advanced diagnostics Magnetic Resonance Entherography (MRE) – a special type of Magnetic Resonance Imaging (MRI) using contrast material – is required, since it shows the mucosa in brilliant white against a black intestine interior. But MRE is costly and not easily accessible even at prestigious and academic hospitals. Furthermore, it is usually perceived as more inconvenient by the patient and handles significantly fewer patients per day compared to a CT scanner.
It is well known that air appears in black – as a so called negative contrast – on X-ray images. But unlike the large intestine, where air can be easily injected through the rectum, there are physiological barriers to aerate the small intestine, making this both difficult and un-friendly to the patient. The scientists behind Lumentin® have solved this problem in an elegant way.
Lumentin® is a food-based contrast agent that provides MRE-class images with the simpler and faster CT-equipment, and with minimal inconvenience for the patient. In parallel with the development of Lumentin®, a smart dispenser and a unique 3-D imaging software is being developed.
An outstanding food based contrast #
Unlike existing contrast agents, which appear bright on the images, Lumentin® gives a black, so-called negative, contrast. This makes it possible to separate the intestinal loops from surrounding organs. When scanning the abdomen with CT, an iodine-based, “white” contrast is injected intra-venously. The contrast agent accumulates especially well in lesions, most of which have increased circulation and therefore stand out in the image. Since the Lumentin®-filled small intestine provides a black background, the mucous membrane’s white interface will appear in bright contrast. This has the potential to make the diagnostic work-up of even minute lesions both faster and more accurate.
Another advantage of Lumentin® is that it is completely food-based and mostly consists of microscopic air bubbles held intact in the small intestine. Also, the production of Lumentin® is in all aspects environmentally friendly.
Lumentin® has undergone clinical tests with very good results. Patient acceptance is very high, and an external audit by leading international radiologists found Lumentin® to fill out the small intestine as effectively as today’s contrast agents, and that it is able to create images with “outstanding” quality, comparable to T1-sequence images from MRE scans.
Lumentin® is simply drunk by the patient prior to the CT scan. Its main ingredients are air and water, and only food-approved substances have been added. This reduces the risk of side effects and patient discomfort, and means a comparably short pathway to drug approval, as no toxicological tests are required.
The Hounsfield Scale #
The Hounsfield scale indicates the contrast produced by different tissues and agents in a CT scan. Full negative – black – contrast is given by air or gas (-1000 HU) while skeleton or metal produces full positive – white – contrast. The scale is named after its inventor, Nobel Prize laureate Sir Godfrey Hounsfield (1919-2004) – one of the pioneers of the computerized tomography technology.
The Future #
Lumentin® is expected to provide completely new opportunities for high quality, image-based abdominal diagnostics with CT technology. This means that MRE scans of the small intestine might well be replaced without sacrificing diagnostic safety, at the same time reducing the waiting time for patients in need for a MRE-scan.
Currently, four clinical trials – internal and multi centre studies – are being planned to verify the results achieved on healthy volunteers and to show expected accuracy in early detection and diagnosis of bowel diseases. The first of the four studies started in November 2017.
In parallel, sensory properties, production methods and user-friendliness in the clinic are under further development. In addition to the contrast agent, the Lumentin®-concept will comprise a smart, safe and labor saving dispenser, as well as an advanced 3-D software that makes it possible to move along and study the inside of the small intestine in detail, based on CT-scan images.
The story #
In 2006 the two radiologists, Thomas Fork and Ingvar Adnerhill, discovered a potential to use a mixture of oat cream and olive oil as a food-based negative contrast agent.
They contacted Prof. Rickard Öste and Prof. Björn Bergenståhl (both at Lund University) and the work begun!
After almost ten years of development and research the first concept of per-oral, food-based negative contrast agent was presented and ready for further clinical evaluation in 2015.
In 2016 the first clinical trial on 25 healthy subjects was performed at Malmö University Hospital (SUS).
After successful phase 2A trials in 2019, phase 2B is ongoing (2020), and phase 3 trials planned for 2021. (see timeline LÄNK)
The Lument Timeline #
2006 – Vision of invention #
Thomas Fork brought up the idea of developing a true negative bowel contrast agent for computer tomography (CT) with a quality comparable to MRE-images. Among the specs were that the agent should be food-based, pleasant to drink, and with no side effects
2009 – Lument AB #
Lument AB was founded for the development of the novel negative contrast agent
March 2016 – Pre-clinical Trial #
Positive results in feasibility studies in vitro digestive tests
2016 – Pilot Trial #
Promising results from an in vivo pilot test with 25 healthy volunteers.
- Excellent contrast
- Acceptable palatability
- No important side effects
- Positive external referees
2017 - Authority approved #
First clinical study on 25 healthy, adult volunteers was conducted with excellent imaging results and high patients’ acceptance.
2017 – Trade mark registration #
Lumentin® registered for the EU trade mark.
Pending: US, Canada, Switzerland, China, UK, Hong Kong and Japan
2017 – Patent applications #
Product portfolio patents pending in Europé, USA, Canada, China, Hongkong, South Africa, India and Australia.
2019 – Phase 2A trials #
Phase 2A-trials were finalized, using Lumentin® as a per-oral filling agent for CT-scans on cancer patients.
2020 – Phase 2B trials #
Phase 2B trials started January 2020 in collaboration with the university hospitals in Malmö and Lund. The one-year trial with Crohn´s patients will compare results of MRE to CT-scans with Lumentin®.
2021 – Phase 3 trials #
European Multicenter Phase 3 trials are planned to start in the beginning of the year, in parallel with commercialization phase.
2022-23 – Registration and commercialization #
European registration of Lumentin as a pharmaceutical for humans and start of sales in the European Union is planned for 2023