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Nuclear medicine
Exciting new diagnostic and therapeutic approaches in prostate cancer with PSMA
02 juli 2020
As Prof. Dr. James Nagarajah, assistant professor Nuclear Medicine at Radboud University in Nijmegen addressed during his talk PSMA Guided Theranostics in Prostate Cancer at NRG at February 1, 2019, the future of prostate cancer (PCa) may be rather exciting. Prostate-specific membrane antigen (PSMA) is a key protein which can be used for diagnostic as well as therapeutic modalities, opening new and promising perspectives for both physicians and patients.
PCa has a high social and economic influence on society as well as impacting the lives of many men worldwide. Approximately one in every seven men is diagnosed with the disease during his lifetime. PCa is not only a leading cause of death in men – 1 in every 38 men will eventually succumb to the disease –, but 30-40% of those that have been initially cured will experience a recurrence of the disease sooner or later. Patients often live many years after diagnosis and PCa survival depends on many aspects such as mutations, severity, staging of the tumor etc. An important distinction in this respect is non-metastatic (localized) disease versus metastatic disease as there are more treatment options available for the first stage of PCa.
Contact NRG
Cora Blankendaal
NRG Press Officer, The Netherlands
The role of PSMA
PSMA is a membrane protein, which has a key role in PCa. The expression of PSMA is PCa specific and increases with tumor grade; when increased, it means higher grade tumors, metastatic disease and hormone-refractory PCa (Figure 1). (Ref. 1,2)
PSMA is a known target for scintigraphy and there are different PSMA ligands: Ga-68 PSMA-11 and F-68 PSMA-1007 among many others; each ligand shows differences in terms of affinity to the target and biodistribution.1,
Figure 1: PSMA expression in different gradations: (Ref. 2)
PSMA in diagnostics
PSMA is a membrane protein, which has a key role in PCa. The expression of PSMA is PCa specific and increases with tumor grade; when increased, it means higher grade tumors, metastatic disease and hormone-refractory PCa (Figure 1). (Ref. 1,2)
PSMA is a known target for scintigraphy and there are different PSMA ligands: Ga-68 PSMA-11 and F-68 PSMA-1007 among many others; each ligand shows differences in terms of affinity to the target and biodistribution.1,
Figure 1: PSMA expression in different gradations: (Ref. 2)
PSMA in therapeutics
PSMA is a membrane protein, which has a key role in PCa. The expression of PSMA is PCa specific and increases with tumor grade; when increased, it means higher grade tumors, metastatic disease and hormone-refractory PCa (Figure 1). (Ref. 1,2)
PSMA is a known target for scintigraphy and there are different PSMA ligands: Ga-68 PSMA-11 and F-68 PSMA-1007 among many others; each ligand shows differences in terms of affinity to the target and biodistribution.1,
Figure 1: PSMA expression in different gradations: (Ref. 2)
The importance of dosimetry
Although imaging can provide physicians detailed and specific information on (progression of the) disease, one thing it does not tell us is dosimetry. Although there have been studies performed on dosimetry with Lu-177 PSMA, only one of these was prospective. In this study by Violet et al., which included 30 patients, dosimetry was performed after cycle 1 with patients receiving up to 4 cycles. It emerged that there was a significant correlation between ‘whole body’ tumor dose and PSA response: if patients receive a whole body tumor dose of mean about 15 Gy, they have a higher chance to have a 50% reduction in serum PSA at 12 weeks. (Ref. 15) These results clearly show that dosimetry is an important pillar in radioligand therapy (RLT) as it allows an individual treatment approach, which is a unique ‘selling’ point in cancer treatment. Assessment of tumor doses, dose-response relationships and doses to organs at risk need to be performed. Pre-treatment dosimetry for individual assessment is desirable as it predicts the dose and enables patient selection: which patient will respond, which will not? This approach prevents patients being treated unnecessarily with agents that are not effect but do have (serious) AEs.
Future directions Radboudumc
Regarding the use of PSMA in the diagnostic and therapeutic field, Radboudumc focuses on a number of topics to be addressed and developed.
• To improve diagnostics with F-18/Ga-68 PSMA PET/(n)MRI
• Individual pre-therapeutic dosimetry (Sc-44, Cu-64, Zr-89…) PSMA. Currently, treatment is done like chemotherapy treatment
• PSMA PET/MRI guided biopsies (local, metastases)
• PSMA PET/MRI guided radiation planning
• Dual labelled (SPECT and fluorescence) PSMA for precise surgery
• Local therapies (cryo, brachy etc.)
• PSMA labelled with alpha/beta emitter for therapy (tandem treatment). PSMA labelled with Lu-177 combined with Ac-225/Pb-212/Tb-161
- Largest irradiator for lutetium-177 globally.
- Controlled reactor conditions ensure your dissolution process.
- We can accurately predict the yield of Lutetium 177