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BackgroundGlioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. 213Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures.Material and methodsAmong 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1–6 doses of 0.9–2.3 GBq 213Bi- DOTA-[Thi8,Met(O2)11]-substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-[Thi8,Met(O2)11]-substance P (68Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI.ResultsTreatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq 213Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.ConclusionsTargeted alpha therapy of secondary GBM with 213Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.

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Background: Microlesion effect (MLE) is a commonly observed phenomenon after electrode insertion into the subthalamic nucleus (STN) for deep brain stimulation (DBS). Objectives: The aim of this study was to determine the presence of the MLE in the early postoperative period and the relationship between MLE and STN DBS. Methods: 74 patients with Parkinson’s disease were included in this study. Motor symptoms were evaluated preoperatively, within 48 h after electrode implantation and at 6 months with United Parkinson’s Disease Rating Scale part III (UPDRS-III). According to the improvement level with MLE, all participants were stratified into three groups: (1) less than 20%; (2) 20–40%, and (3) more than 40% in OFF medication states. The degree of improvement in UPDRS-III with DBS ON for each MLE group was assessed at the 6-month follow-up. Regression analysis was applied for the evaluation of the relationship between MLE and improvement with DBS ON. Results: Mean results in UPDRS-III with the MLE in ON and OFF medication states were 22.1 ± 10.5 and 42.1 ± 14 points, respectively. At the 6-month follow-up, with active stimulation, results tended to further ameliorate to 14.6 (59.4%) points in ON and 20.8 (55.3%) in OFF. Mean improvement in MLE groups were: 33.6% group 1, 47.5% group 2 and 61.4% group 3. Regression analysis revealed a positive correlation between the MLE and results at 6 months with DBS ON. Conclusion: Results proved the presence of MLE in the early postoperative period. Furthermore, a positive correlation between MLE and improvement degree with active stimulation was observed.

Background Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. After initial therapy and total resection of GBM, 80% to 90% of recurrences occur at the surgical margins. Currently, limited data are available in the literature on the possible use of 68Ga–prostate-specific membrane antigen (PSMA-11) for diagnosis of recurrence in GBM patients. The aim was to assess the feasibility and potential of 68Ga-PSMA-11 PET/CT as a diagnostic procedure in patients with histologically confirmed of GBM and suspected recurrent disease on MRI. Results No radiopharmaceutical-related adverse events were noted. Characterization of recurrent disease with MRI included T2-weighted fast spin-echo images, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, and gadolinium enhanced T1-weighted images. Visual interpretation of PET showed increased accumulation of 68Ga-PSMA-11 in recurrent lesion detected by T1 contrast enhanced and diffusion-weighted imaging images in all patients with a median SUVmax of the tumor of 6.5 and an SUVmean of 3.5. The median tumor-to-background brain ratio and tumor-to-liver ratio obtained from 68Ga-PSMA-11 PET/CT were 96.7 and 0.8, respectively. Conclusions The extremely low background uptake in normal brain tissue and consequently high tumor-to-brain ratio make 68Ga-PSMA-11 PET/CT highly promising for diagnosis of recurrent disease in GBM patients. Although PSMA expression in recurrent GBM also opens a potential way for targeted peptide therapy with α/β-emitters as well as for prediction of treatment with antiangiogenic agents, the low tumor-to-liver ratio observed in the majority of patients in this study suggests a limited role of radiolabeled PSMA ligands for targeted radionuclide therapy of recurrent GBM.