Theranostic PSMA Radioligands/Radiotracers

Radiopharmaceutical Drug Development in Cancer Research: The Theranostic Radiotracer Approach

We are deeply involved in the design and development of tailor-made PSMA-targeted theranostic radiotracers which are used for noninvasive PET/CT and PET/MRI imaging and for internal radioligand-assisted therapy, i.e. endoradiotherapy, of prostate cancer (PCa). In 2011 the PET tracer 68Ga-PSMA-11 was clinically introduced for PCa imaging in the Department of Nuclear Medicine of the Heidelberg University Hospital. This promising PSMA-PET tracer was developed in the Division of Radiopharmaceutical Chemistry (DKFZ) and is meanwhile going to be examined in the DKTK-funded multicenter prospective clinical trial (phases-I & -II) 68Ga-PSMA-11 in high-risk prostate cancer (Sponsor DKFZ Heidelberg) with 11 participating decentralized radiopharmacies and nuclear medicine clinics within the D-A-CH region. This endeavor is recognized as one of the defined DKTK highlight projects and is currently supported by the DKTK Joint Funding Program.

Staging of a patient with mestatic castration-resistant PCa with the new PET tracer 18F-PSMA-1007 receiving 177Lu-PSMA-617 therapy: both compounds show a very similar uptake pattern (qualitatively). 18F-PSMA-1007 PET delivers a clear delineation of metastases.

Since 2013 we started an initiative to transform PSMA-11 into the theranostic version PSMA-617 which can be radiolabelled with the therapeutically relevant trivalent radiometals lutetium-177 for beta therapy and actinium-225 for alpha therapy. PSMA-617 has recently entered the agenda of the German Society of Nuclear Medicine (DGN e.V.). Additionally, not long ago a consortial project was founded entitled German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced PCa Patients to initiate a prospective multicenter clinical trial (phases-II & -III).

Due to the currently highly increasing clinical demand there is also a strong need for 18F-labelled PSMA ligands (T1/2: 110 min) for PET/CT and PET/MRI hybrid imaging, in addition to 68Ga-labelled PSMA radiotracers (T1/2: 68 min), to cover the daily patient examinations. Using PSMA-617 as the lead structure, the PET tracer 18F-PSMA-1007 has been developed by our group, an ideal and promising prostate PET imaging agent, especially useful for the primary diagnosis of PCa and imaging of local relapse. Currently, the clinical potential of this attractive PSMA-PET radioligand is being explored and a first prospective clinical trial (phases-I & -II) is being planned (PI/LKP: Frederik Giesel, Coordinator Radiopharmacy: Klaus Kopka). As PSMA-1007 is derived from PSMA-617, both tracers (18F-PSMA-1007 and 177Lu-PSMA-617) can be used as a theranostic tandem of PSMA radioligands. Both compounds are already licensed to an industrial partner during the last couple of years.


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