IMPORTANCE Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.OBJECTIVE To investigate the potential of the novel tau radiotracer 18 F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, participants underwent dynamic 18 F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans.

We evaluated the accuracy of PET/CT with 68 Ga-PSMA-HBED-CC-a 68 Ga-conjugated ligand of human prostate-specific membrane antigen (PSMA)-to localize cancer in the prostate and surrounding tissue at initial diagnosis. Methods: Twenty-one patients with biopsy-proven prostate cancer underwent 68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA) PET/CT at a median of 4 d (range, 0-47 d) before radical prostatectomy. Based on a 6-segment model, the Gleason score and proportion of tumor tissue within each segment (segmental tumor burden, or STB) as determined by histopathology (STB HP ) were correlated with SUV max and STB as determined by different SUV cutoffs for 68 Ga-PSMA PET (STB ). Furthermore, the involvement of seminal vesicles and other extracapsular extension were assessed by histopathology and PET/CT. Results: Histopathology-positive segments (n 5 100 of 126; 79%) demonstrated a significantly higher mean ± SD SUV max (11.8 ± 7.6) than histopathology-negative segments (4.9 ± 2.9; P , 0.001). Receiver-operating-characteristic analysis revealed an optimal SUV max cutoff of 6.5 for discrimination of histopathology-positive segments from histopathology-negative segments (area under the curve, 0.84; P , 0.001), which gave 67% sensitivity, 92% specificity, a 97% positive predictive value, a 42% negative predictive value, and 72% accuracy. STB PET3 as determined by (2 · blood SUV) 1 (2 · SD) correlated best with STB HP (Pearson ρ 5 0.68; P , 0.001; mean difference ± SD, 19% ± 15%). PET/CT correctly detected invasion of seminal vesicles (n 5 11 of 21 patients; 52%) with 86% accuracy and tumor spread through the capsule (n 5 12; 57%) with 71% accuracy. Conclusion: 68 Ga-PSMA PET/CT accurately detected the location and extent of primary prostate cancer. Our preliminary findings warrant further investigation of 68 Ga-PSMA PET/CT in conjunction with needle biopsy.

We recently demonstrated tumor-selective iodide uptake and therapeutic efficacy of radioiodine in neuroblastoma tumors after systemic nonviral polyplex-mediated sodium iodide symporter (NIS) gene delivery. In the present study, we used novel polyplexes based on linear polyethylenimine (LPEI), polyethylene glycol (PEG), and the synthetic peptide GE11 as an epidermal growth factor receptor (EGFR)-specific ligand to target a NIS-expressing plasmid to hepatocellular carcinoma (HCC) (HuH7). Incubation of HuH7 cells with LPEI-PEG-GE11/NIS polyplexes resulted in a 22-fold increase in iodide uptake, which was confirmed in other cancer cell lines correlating well with EGFR expression levels. Using (123)I-scintigraphy and ex vivo γ-counting, HuH7 xenografts accumulated 6.5-9% injected dose per gram (ID/g) (123)I, resulting in a tumor-absorbed dose of 47 mGray/Megabecquerel (mGy/MBq) (131)Iodide ((131)I) after intravenous (i.v.) application of LPEI-PEG-GE11/NIS. No iodide uptake was observed in other tissues. After pretreatment with the EGFR-specific antibody cetuximab, tumoral iodide uptake was markedly reduced confirming the specificity of EGFR-targeted polyplexes. After three or four cycles of polyplex/(131)I application, a significant delay in tumor growth was observed associated with prolonged survival. These results demonstrate that systemic NIS gene transfer using polyplexes coupled with an EGFR-targeting ligand is capable of inducing tumor-specific iodide uptake, which represents a promising innovative strategy for systemic NIS gene therapy in metastatic cancers.

Due to its dual role as reporter and therapy gene, the sodium iodide symporter (NIS) allows noninvasive imaging of functional NIS expression by (123)I-scintigraphy or (124)I-PET imaging before the application of a therapeutic dose of (131)I. NIS expression provides a novel mechanism for the evaluation of mesenchymal stem cells (MSCs) as gene delivery vehicles for tumor therapy. In the current study, we stably transfected bone marrow-derived CD34(-) MSCs with NIS cDNA (NIS-MSC), which revealed high levels of functional NIS protein expression. In mixed populations of NIS-MSCs and hepatocellular cancer (HCC) cells, clonogenic assays showed a 55% reduction of HCC cell survival after (131)I application. We then investigated body distribution of NIS-MSCs by (123)I-scintigraphy and (124)I-PET imaging following intravenous (i.v.) injection of NIS-MSCs in a HCC xenograft mouse model demonstrating active MSC recruitment into the tumor stroma which was confirmed by immunohistochemistry and ex vivo γ-counter analysis. Three cycles of systemic MSC-mediated NIS gene delivery followed by (131)I application resulted in a significant delay in tumor growth. Our results demonstrate tumor-specific accumulation and therapeutic efficacy of radioiodine after MSC-mediated NIS gene delivery in HCC tumors, opening the prospect of NIS-mediated radionuclide therapy of metastatic cancer using MSCs as gene delivery vehicles.

ObjectivesIn recent years several [18F]-labelled amyloid PET tracers have been developed and have obtained clinical approval. There is accumulating evidence that early (post injection) acquisitions with these tracers are equally informative as conventional blood flow and metabolism studies for diagnosis of Alzheimer's disease, but there have been few side-by-side studies. Therefore, we investigated the performance of early acquisitions of [18F]-florbetaben (FBB) PET compared to [18F]-fluorodeoxyglucose (FDG) PET in a clinical setting.MethodsAll subjects were recruited with clinical suspicion of dementia due to neurodegenerative disease. FDG PET was undertaken by conventional methods, and amyloid PET was performed with FBB, with early recordings for the initial 10 min (early-phase FBB), and late recordings at 90–110 min p.i. (late-phase FBB). Regional SUVR with cerebellar and global mean normalization were calculated for early-phase FBB and FDG PET. Pearson correlation coefficients between FDG and early-phase FBB were calculated for predefined cortical brain regions. Furthermore, a visual interpretation of disease pattern using 3-dimensional stereotactic surface projections (3D-SSP) was performed, with assessment of intra-reader agreement.ResultsAmong a total of 33 patients (mean age 67.5 ± 11.0 years) included in the study, 18 were visually rated amyloid-positive, and 15 amyloid-negative based on late-phase FBB scans. Correlation coefficients for early-phase FBB vs. FDG scans displayed excellent agreement in all target brain regions for global mean normalization. Cerebellar normalization gave strong, but significantly lower correlations. 3D representations of early-phase FBB visually resembled the corresponding FDG PET images, irrespective of the amyloid-status of the late FBB scans.ConclusionsEarly-phase FBB acquisitions correlate on a relative quantitative and visual level with FDG PET scans, irrespective of the amyloid plaque density assessed in late FBB imaging. Thus, early-phase FBB uptake depicts a metabolism-like image, suggesting it as a valid surrogate marker for synaptic dysfunction, which could ultimately circumvent the need for additional FDG PET investigation in diagnosis of dementia.