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Objectives: To identify predictors of early oncological outcomes in patients who opt for robot-assisted laparoscopic radical prostatectomy (RARP) for localized prostate cancer (PCa), including conventional prognostic variables as well as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET)., Patients and Methods: This observational study included 493 patients who underwent RARP and extended pelvic lymph node dissection (ePLND) for unfavourable intermediate- or high-risk PCa. Outcome measurement was biochemical progression of disease, defined as any postoperative prostate-specific antigen (PSA) value ≥0.2 ng/mL, or the start of additional treatment. Cox regression analysis was performed to assess predictors for biochemical progression, including initial PSA value, biopsy Grade Group (GG), T-stage on mpMRI, and lymph node status on PSMA PET imaging (miN0 vs miN1)., Results: The median (interquartile range) total follow-up of all included patients without biochemical progression was 12.6 (7.5-22.7) months. When assessing biochemical progression after surgery, initial PSA value (per doubling; odds ratio [OR] 1.22, 95% confidence interval [CI] 1.07-1.40; P = 0.004), biopsy GG ≥4 vs GG 1-2 (OR 1.83, 95% CI 1.18-2.85; P = 0.007), T-stage on mpMRI (rT3a vs rT2: OR 2.13, 95% CI 1.39-3.27; P = 0.001; ≥rT3b vs rT2: OR 4.78, 95% CI 3.20-7.16; P < 0.001) and miN1 on PSMA PET imaging (OR 2.94, 95% CI 2.02-4.27; P < 0.001) were independent predictors of early biochemical progression of disease., Conclusion: Initial PSA value, biopsy GG ≥4, ≥rT3 disease on mpMRI and miN1 disease on PSMA PET were predictors of early biochemical progression after RARP. Identifying these patients with an increased risk of early biochemical progression after surgery may have major implications for patient counselling in radical treatment decisions and on patient selection for modern (neo-)adjuvant and systematic treatments., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are membrane efflux pumps that may have a role in the kinetics of (99m)Tc-sestamibi (MIBI) in parathyroid tumors. P-gp and MRP1 expression in parathyroid tumors was studied and related to histology, weight and pre- and intraoperative MIBI imaging results., Design: Patient cohort study, Setting: Tertiary referral center, Patients: Thirty-three patients underwent radioguided parathyroidectomy for primary or secondary hyperparathyroidism., Main Outcome Measures: P-gp and MRP1 expression., Methods: Dual-phase (99m)Tc-MIBI scintigraphy and SPECT results were compared to the surgical findings. Radioactivity and weight of resected parathyroid tumors were measured. Intraoperative radioactivity measurements were decay corrected. After routine histology immunohistochemistry was performed using C494 monoclonal antibodies to P-gp and MRP1r1 to MRP1. P-gp and MRP1 expression were scored covering both distribution of positivity and degree of immunostaining semi quantitatively., Results: P-gp and MRP1 staining was observed in 97% and 43% of the glands respectively. P-gp staining was positive in 91% (21/23) of the adenomas and in all 36 hyperplastic glands. MRP1 staining was positive in 22% (5/23) of the adenomas and in 61% (22/36) of the hyperplastic glands. P-gp or MRP1 expression did not correlate with preoperative (99m)Tc-MIBI imaging or intraoperative radioactivity. Parathyroid weight was associated with preoperative MIBI imaging results and MIBI uptake measured during surgery., Conclusion: P-gp and MRP1 expression did not correlate with (99m)Tc-MIBI uptake in parathyroid tumors. Parathyroid weight remains the major known factor influencing (99m)Tc-MIBI uptake., (J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart.New York.)

Unlabelled: Serotonin-1A (5-hydroxytryptamine-1A [5-HT1A]) receptors have been reported to play an important role in the pathophysiology of a variety of psychiatric and neurodegenerative disorders. Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2'-pyridinyl)-p-[18F]fluorobenzamido ]ethylpiperazine ([18F]MPPF) may be suitable for 5-HT1A receptor imaging in humans. The aim of this study was to determine if [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor densities in brain regions of healthy human volunteers., Methods: [15O]H2O perfusion scanning was performed before intravenous injection of [18F]MPPF to obtain anatomic information. Cerebral radioactivity was monitored using a PET camera. Plasma metabolites of [18F]MPPF were determined by high-performance liquid chromatography. Binding potentials were calculated using the metabolite-corrected arterial input function and a linear graphic method (Logan-Patlak analysis)., Results: The highest levels of radioactivity were observed in the medial temporal cortex, especially in the hippocampal area. In contrast, the cerebellum and basal ganglia showed low uptake of 18F, in accordance with known 5-HT1A receptor distribution. The calculated binding potentials correlated well with literature values for 5-HT1A receptor densities. The binding potentials for [18F]MPPF were 4-6 times lower than those that have been reported for [carbonyl-1C]-(N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyrid yl) cyclohexane-carboxamide (WAY 100635), indicating that [18F]MPPF has a lower in vivo affinity for 5-HT1A receptors., Conclusion: These results confirm that [18F]MPPF can be used for the quantitative analysis of 5-HT1A receptor distribution in the living human brain. The rapid dissociation from the receptor makes this ligand a possible candidate to monitor changes in endogenous serotonin levels.

Animal experiments have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido+ ++] ethylpiperazine ([(18)F]p-MPPF) can be used for 5-hydroxytryptamine(1A) (5-HT(1A)) receptor imaging. The aim of this study was to develop a method for the quantitative imaging of 5-HT(1A) receptors in healthy volunteers with [(18)F]p-MPPF. After injection of [(18)F]p-MPPF radioactivity was rapidly taken up in the brain, with the highest accumulation in the medial temporal cortex. Low levels of radioactivity were found in cerebellum and basal ganglia. Plasma clearance and metabolism of [(18)F]p-MPPF resulted in only about 1% of the radioactivity in plasma as parent radioligand after 10 min. Using a linear graphical method (Logan-Patlak), binding potentials were calculated in several brain areas. A good correlation (r = 0.95) was found between the obtained binding potentials and literature values for 5-HT(1A) receptor densities. A good correlation (r = 0.96) was also found between the body weight-corrected region/cerebellum ratios and the respective binding potentials. Moreover, a blocking experiment with pindolol (n = 3) showed a decrease of 40% in the region/cerebellum ratios of the target areas. Compared to those of [carbonyl-(11)C]WAY-100635, the binding potentials were four to six times lower, indicating that [(18)F]p-MPPF has a lower in vivo affinity for 5-HT(1A) receptors. In conclusion, [(18)F]p-MPPF can be used for the quantitative analysis of 5-HT(1A) receptor distribution in human brain.