Post-Surgical Auger Electron Therapy of Prostate Cancer Patients with Localized Disease: Development and Assessment of a New Concept for High-Risk Patients – PHRT
Post-Surgical Auger Electron Therapy of Prostate Cancer Patients with Localized Disease: Development and Assessment of a New Concept for High-Risk Patients
In this project, Auger-e‒-emitting radionuclides should be investigated in combination with ligands for targeting PSMA, a frequently expressed protein on prostate cancer tissue. Post-surgical application of such novel radioligands is thought to provide prostate cancer patients with localized disease, but high risk of relapse after surgery, with a better long-term prognosis.
The aim of this study is to develop a novel personalized post-surgical therapy concept using tailor-made Auger-e‒-emitting PSMA ligands. The proposed concept is thought to provide a specific class of prostate cancer patients, characterized by localized disease, but high risk of relapse after surgery, with a better long-term prognosis.
With this proposal we aim at achieving a critical step towards a personalized approach of prostate cancer treatment by means of PSMA-targeting using non-standard radionuclides for post-surgical eradication of surviving cancer cells. It is expected that after this PhD thesis, it is known (i) whether PSMA is a valid tumor target for this specific class of patients, (ii) whether it is possible to achieve PSMA targeting followed by shuttling the radioligand into the cellular nucleus and, (iii) whether Auger-e‒-emitting radionuclides would be more suited than pure β‒- particle emitters to effectively kill these cancer cells. Most importantly, it will be known (iv) whether post-surgical Auger-e‒ therapy can reduce the cases of relapse after removal of the primary tumor mass based on the in vitro/ex vivo and in vivo data obtained in diverse personalized preclinical models including organoids, tissue cultures and patient-derived xenograft (PDX)-models.
Dependent on the achieved results in the scope of these PhD studies, it is proposed to translate the concept to clinics. Being the first world-wide to demonstrate effective Auger-e‒ therapy after surgical removal of the tumor mass and, therewith, improve the prognosis of this specific class of patients would mean a break-through in the respective fields and an immeasurable credit to a large number of patients who currently live – in spite of the good prognosis due to absence of metastases – in constant fear due to the risk of relapse.
Prostate cancer is the most frequently diagnosed malignancy and second leading cause of cancer-specific deaths in men in Western countries. Prostate cancer manifestations can vary from indolent localized tumors to widespread metastases. The prostate-specific membrane antigen (PSMA) evolved as a very promising protein for targeting with radioactive ligands, a therapy concept currently implemented at many sites worldwide for patients with metastatic disease. The question arises on whether PSMA-targeted radionuclide therapy using Auger-e–emitting radionuclides could be employed for patients with localized disease, enabling post-surgical killing of surviving cancer cells and, hence, increase the prognosis of this specific class of prostate cancer patients.
Patents / Startups
Borgna & L. M. Deberle, S. D. Busslinger, V. J. Tschan, L. M. Walde, A. E. Becker, R. Schibli, C. Müller, “Preclinical investigations to explore the difference between the diastereomers [177Lu]Lu-SibuDAB and [177Lu]Lu-RibuDAB towards prostate cancer therapy”, Mol Pharm, Jul 2022, 19 (7): 2105-2114, doi: 10.1021/acs.molpharmaceut.1c00994
D. Busslinger & V. J. Tschan, O. K. Richard, Z. Talip, R. Schibli, C. Müller, “[225Ac]Ac-SibuDAB for Targeted Alpha Therapy of Prostate Cancer: Preclinical Evaluation and Comparison with [225Ac]Ac-PSMA-617”, Cancers, Nov 2022, 14 (22): 5651, doi: 10.3390/cancers14225651
J. Tschan, F. Borgna, R. Schibli, C. Müller, “Impact of the mouse model and molar amount of injected ligand on the tissue distribution profile of PSMA radioligands”, Eur J Nucl Med Mol Imaging, Jan 2022, 49 (2): 470-480. doi: 10.1007/s00259-021-05446-5.
J. Tschan, F. Borgna, S. D. Busslinger, M. Stirn, J. M. Monné-Rodriguez, P. Bernhardt, R. Schibli, C. Müller, “Preclinical investigations using [177Lu]Lu-Ibu-DAB-PSMA towards its clinical translation for radioligand therapy of prostate cancer”, Eur J Nucl Med Mol Imaging, Sep 2022, 49 (11): 3639-3650, doi: 10.1007/s00259-022-05837-2
Viviane J. Tschan, Sarah D. Busslinger, Peter Bernhardt, Pascal V. Grundler, Jan Rijn Zeevaart, Ulli Köster, Nicholas P. van der Meulen, Roger Schibli and Cristina Müller
Journal of Nuclear Medicine July 2023, jnumed.123.265524; DOI: https://doi.org/10.2967/jnumed.123.265524
Patents / Startups
Dr. Cristina Müller
Paul Scherrer Institute (PSI), Center for Radiopharmaceutical Sciences