ITM Isotopen Technologien München AG, a specialized radiopharmaceutical company, announced that the European Medicines Agency (EMA) has granted Marketing Authorization for EndolucinBeta of ITM´s subsidiary ITG Isotope Technologies Garching GmbH. This decision follows a positive recommendation from the European Committee for Medicinal Products for Human Use (CHMP) in May of this year.

EndolucinBeta respectively no-carrier-added (n.c.a.) Lutetium (177Lu) chloride is used in Targeted Radionuclide Therapy, e.g. in the field of precision oncology. It is a radiopharmaceutical precursor, used for radiolabeling of disease-specific carrier molecules, like antibodies or peptides. 177Lu has successfully been used for the treatment of inoperable or metastasized neuroendocrine tumors (NET) by radiolabeling with Somatostatin analogues1 for example with the peptide DOTATOC (Edotreotide). Somatostatin receptors are predominantly overexpressed by NETs. The radiopharmaceutical, upon binding to the Somatostatin receptor is in vivo internalized and retained by tumor cells. Upon decay, 177Lu emits cytotoxic medium-energy beta particles with a maximum range of 1.7 mm in soft tissue, which means that healthy tissue in the surroundings of the targeted tumor is minimally affected.

Currently EndolucinBeta is successfully used in investigational medicinal products for radiolabeling of peptides or antibodies. A recently published retrospective phase II study with DOTATOC radiolabeled with EndolucinBeta showed promising efficacy and safety data. These results suggest and demonstrate a significant benefit, a substantially improved progression-free survival (PFS), for which n.c.a. 177Lu-DOTATOC received an Orphan Designation (EMA/OD/196/13) as a treatment of gastro-entero-pancreatic neuroendocrine tumors (GEP-NET).

Steffen Schuster, chief executive officer of the ITM Group, commented, “We are very pleased that EndolucinBeta now received Marketing Authorization. In the past promising results have already been achieved by combining EndolucinBeta with disease-specific targeting molecules for Radionuclide Therapy especially with DOTATOC. In the future these encouraging results of n.c.a. 177Lu-DOTATOC need to be confirmed in a multi-center phase III study.”

EndolucinBeta is a radiopharmaceutical precursor with a half-life of 6.647 days, usable for radiolabeling of disease-specific carrier molecules. The active substance of EndolucinBeta is nocarrier- added (n.c.a.) Lutetium (177Lu) chloride. No-carrier-added 177Lu provides the highest specific activity of more than 3,000 GBq/mg at Activity Reference Time (ART), whereas the day of ART can be flexibly selected by the customer. Optimal preconditions for efficient radio labeling of biomolecules over its entire shelf-life of 9 days after production are ensured. Furthermore EndolucinBeta exhibits an extraordinary level of radionuclidic purity. EndolucinBeta does not contain metastable 177mLu, thus, there is no need of logistics and storage of contaminated radioactive waste.

Targeted radionuclide therapy is a medical specialty using very small amounts of radioactive compounds, called radiopharmaceuticals, to diagnose and treat various diseases, like cancer. Targeted radiopharmaceuticals contain a targeting molecule (e.g. peptide or antibody) and a medical radioactive isotope. The targeting molecule binds to a tumor specific receptor, according to the lock and key principle. In most cases the targeting molecule can be used for both diagnosis and therapy - only the radioisotope has to be changed. This opens up the way for the application of Theranostics in the field of precision oncology.

For diagnostic applications radioisotopes with short half-lives are used. With highly sensitive molecular imaging technologies like PET (Positron Emission Tomography) or SPECT (Single Photon Emission Tomography), pictures of organs and lesions can be created and diseases can therefore be diagnosed in their early stages. Medical radioisotopes with longer half-lives are applied for treatment. To destroying the tumor minimal cytotoxic doses of ionizing radiation have to be submitted to the tumor site before decay. A highly precise localization of the toxicity ensures that healthy tissue in the surroundings of the targeted tumor is minimally affected.