DOTATATE; Automated radiotracer production; Clinical Phase I study; Good Manufacturing Practice; Molecular imaging; Scandium-43/44; Isotope production; Neuroendocrine tumors; Cancer diagnosis; Radiopharmacy
Müller Cristina, Umbricht Christoph A., Gracheva Nadezda, Tschan Viviane J., Pellegrini Giovanni, Bernhardt Peter, Zeevaart Jan Rijn, Köster Ulli, Schibli Roger, van der Meulen Nicholas P. (2019), Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer, in European Journal of Nuclear Medicine and Molecular Imaging
, 46(9), 1919-1930.
Umbricht Christoph A., Benešová Martina, Schmid Raffaella M., Türler Andreas, Schibli Roger, van der Meulen Nicholas P., Müller Cristina (2017), 44Sc-PSMA-617 for radiotheragnostics in tandem with 177Lu-PSMA-617—preclinical investigations in comparison with 68Ga-PSMA-11 and 68Ga-PSMA-617, in EJNMMI Research
, 7(1), 9-9.
Domnanich Katharina A., M?ller Cristina, Farkas Renata, Schmid Raffaella M., Ponsard Bernard, Schibli Roger, T?rler Andreas, van der Meulen Nicholas P. (2017), 44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations, in EJNMMI Radiopharmacy and Chemistry
, 1(1), 8-8.
Honarvar H., Müller Cristina, Cohrs Susan, Haller Stephanie, Westerlund K., Karlstrom A. E., van der Meulen N. P., Schibli Roger, Tolmachev V. (2017), Evaluation of the first 44Sc-labeled Affibody molecule for imaging of HER2-expressing tumors, in Nuclear Medicine & Biology
, 45, 15-21.
Singh A., van der Meulen N. P., Müller C., Klette I., Kulkarni H. R., Türler A., Schibli Roger, Baum Richard (2017), First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study, in Cancer Biother Radiopharm
, 32(4), 124-132.
Background and Aims: Radiopharmaceuticals or radiotracers that comprise metallic radionuclides have proven to be valuable diagnostic and therapeutic tools in oncology. For the management of patients suffering from neuroendocrine tumours (NET) in particular, radiometal-labelled somatostatin analogues are readily used for both diagnosis and therapy. Radiosomatostatin analogues such as 111In-octreotide and 68Ga-DOTA-Tyr3-Octreotate (for diagnosis) and 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-Octreotate (for therapy) represent the current bench-mark. It is apparent, however, that 111In-octreotide results in scintigrams or SPECT (Single Photon Emission Computed Tomography) of poor quality. The PET (Positron Emission Tomography) tracer 68Ga-DOTA-Tyr3-Octreotate has been clinically proven to be a better alternative to 111In-octreotide because of its better pharmacokinetics and, thus, image quality. 68Ga (T1/2 = 68 min), however, is not an ideal radionuclide for centralised tracer production and quality control - which is firmly believed to be the future of radiopharmacy - with distribution to the numerous nuclear medical centres in Switzerland and India, despite the availability of 68Ge/68Ga generators, being problematic. PET radionuclides with longer physical half-lives, but providing similar image quality, therefore, have to be evaluated. The aim of this Indo-Swiss Joint Research Project is to perform true translational biomedical research (bech-to-bedside) by developing and clinically assess a radiosomatostatin analogue with novel, longer-lived PET radionuclides. This will have a positive impact on the management of NET patients in India and Switzerland.Methods: It is aimed to develop the production of the positron-emitting radionuclide 44Sc (useful for Positron Emission Tomography, PET; T1/2 = 3.97 h; E?? = 1475 keV, 94.3%) and its diagnostic counterpart, 43Sc (T1/2 = 3.9 h; maxE?? = 1198 keV; E? = 372 keV) in quantities and quality useful for medical purposes in Switzerland (Paul Scherrer Institut) and India. It is planned to use these radionuclides to label the well-characterized somatostatin analogue DOTA-Tyr3-Octreotate under GMP conditions in India (Institute of Nuclear Medicine & Allied Sciences, INMAS - Delhi, Postgraduate Institute of Medical Education & Research, PGIMER - Chandigarh, Sanjay Gandhi Post Graduate Institute of Medical Sciences, SGPGI - Lucknow) and Switzerland (Paul Scherrer Institute - Villigen). The resulting 44Sc/43Sc-DOTA-Tyr3-Octreotate will be evaluated (and compared) in a clinical proof-of-concept study in a limited number of patients (typically 5-10 patients per centre and/or radionuclide) at the Nuclear Medical Departments of the abovementioned Indian institutes, as well as University Hospital Zurich. The tracers will be assessed with respect to their in vivo pharmacokinetic imaging capacity, as well as the total radiation dose to the patients in a head-to-head comparison with 68Ga-DOTA-Tyr3-Octreotate.Expected impact: Should this project be successful, two new radionuclides will be introduced to the portfolio of nuclear medicine. Due to their physical decay properties, they will be almost ideal for a centralised production and easy and economic distribution of their corresponding radiopharmaceuticals. 44Sc/43Sc-DOTA-Tyr3-Octreotate tracer availability for NET diagnosis will dramatically facilitate patient management for NTEs in India and Switzerland by making novel tracers available for a large number of nuclear medical centres. 44Sc-DOTA-Tyr3-Octreotate will serve as a prototype for other radiometal-based radiopharmaceuticals, especially novel peptide-based radiopharmaceuticals. Additionally, this project will cement Switzerland’s role in tracer and radionuclide development, while fostering India with regard to developing and bringing new, innovative radionuclides to the country’s nuclear medicine fraternity. The radionuclides and the corresponding radiotracers have the potential to be commercially exploited by industrial partners. Young scientists will also be trained in areas such as radiochemistry, radiopharmaceutical chemistry and GMP production of radiopharmaceuticals. Aside from the diagnostic power of 44/43Sc, this project possesses an inherent therapeutic component for the future by switching from 44/43Sc to the therapeutic match, 47Sc. This enhances the proposed project’s attraction for the scientific and medical community and may provide a long-term perspective for the project and the consortium as a whole. As a result, an additional dynamic impulse towards the development of new and effective radiodiagnostics and therapeutics for the management of cancerous diseases can also be expected. The studies mutually profit from capabilities of unique sites in India, as well as in Switzerland, and the know-how of local experts in the field of radiochemistry and radiopharmacy.