Diagnostic marker for quantitative imaging of beta cells based on novel radiolabeled exendin peptides
TransMIT Gesellschaft für Technologietransfer mbH
The novel radiolabeled exendin derivatives provide a highly specific diagnostic tool for the detection of beta cells in the pancreas of patients at risk of developing diabetes or already having diabetes. An imaging protocol has been developed that allows single time point quantitative SPECT/CT imaging to allow for simple, time-efficient clinical imaging.
The product is ready-to-use for clinical applications and gives for the first time the opportunity for detection of changes in beta cell mass in persons with diabetes or at risk to develop the disease. The possibility of beta cell mass quantification is furthermore associated to the chance of validation of therapy success with already available medicaments or new drug candidates that may preserve or increase beta cell mass.
Product description and business opportunities
With the new exendin derivatives peptides are available which are recognised and specifically bound by GLP-1 receptor that is expressed on beta cells of the pancreas. The new exendin peptides can be labelled in diverse ways with radioactive nuclides, fluorescent dyes, or MRI contrast agents that allows for the in vivo quantification of the beta cell mass in the pancreas for the first time (namely the density of insulin producing cells) through external imaging, which opens completely new possibilities in the early diagnosis and treatment of diabetes mellitus. Even the response to medication in the treatment of diabetes mellitus is thereby measurable and thus an optimisation of the medical therapy combined with reduced costs is possible. Furthermore, these peptides are applicable in the diagnosis of tumours such as insulinoma.
Market, fields of application and market trends
The market for diabetes diagnostics was 3.6 Billion US$ in Europe in 2008, and it is suggested that the market will be 10.6 Billion US$ in the EU in 2015. This is due to the policy of the European countries that trigger innovations leading to early diagno-sis of diabetes in order to prevent high therapy costs due to secondary disorders. The novel technology opens a window of opportunity for diabetes research, diagnostics and therapy:
- patient stratification for therapy
- beta cell protection/recovery
- patient characterization etc.
Unique selling points (USP)
In contrast to the detection methods currently available on the market, the novel peptides offer the following advantages:
- Quantifiable mass determination of insulin-producing cells (beta cells) in the pancreas
- Diagnosis of GLP-1-receptor expressing tumours, especially insulinomas, for which sufficiently sensitive non-invasive procedures are warranted
- Diagnosis is carried out by means of GLP-1 receptor scintigraphy (SPECT) or Positron Emission Tomography (PET)
- Wide possibilities in the labelling of the peptides through coupling with radionuclides, MRI contrast agents, fluorescent dyes and/or therapeutic agents
As shown by a first clinical study, the uptake of the radiolabeled peptide is lower in the group with type 1 diabetes (T1D) but not diminished in all T1D subjects. Alt-hough this may be surprising at the first glance, as since the 1960s it is suggested that T1D patients have a beta cell mass reduced by 90% or more, there is a growing body of more recent evidence suggesting that T1D patients still have remaining beta cells. Our data are perfectly in line with these data:
- The maximum difference in pancreatic uptake between healthy volunteers and patients with T1D is ~10 fold.
- Pancreatic uptake varies by a factor of 4-5 between individuals, which is in line with the literature (Ritzel et al, Diabetes Care. 2006; 29(3):717-8).
- In part of the T1D patients, there is residual radiotracer uptake; this may reflect remaining (afunctional) BCM in T1D patients (Coppieters et al, J. Exp. Med. 2012; 209 (1): 51-60).
- Differential quantitative analysis of the radiotracer distribution in the pancreas shows a distinct pattern which is in line with recent data about the distribution of islets in complete pancreata (Zielinski et al., Quantitative patho-physiological analysis of the whole human pancreas; NIH workshop “Imaging the Pancreatic Beta Cell”, Bethesda, MD, USA, 15/16 April 2013).
Product development status
The peptides were synthesized according to GMP standard, and the available amount is suitable for clinical investigation of several tenthousand persons. The peptides were tested in an acute toxicity study without any signs of toxicity. Furthermore, stability testing as well as pharmacological studies and dosimetry was performed. An IMPD dossier is available. Kits (ready-to-use or for on-site labeling) are available for distribution in Europe.
A German priority application was filed on 3rd September 2004, and an international PCT application was filed on 26th August 2005, claiming priority of the first German application. Three divisional applications were filed, and the patents for exendin-4, exendin-3, and GLP-1 peptide derivatives are granted in EU, US and other countries worldwide or are pending.
Possibility for cooperation
TransMIT is looking for cooperation partners for the distribution in Europe, USA, and Asia. After signing a non-disclosure agreement, you will be provided with the opportunity to consult market analysts, innovation managers, and the experts/scientists responsible for the new product in order to gain greater insight into the new technology and business opportunities arising from this.