59 research outputs found
Toward the discovery and development of PSMA targeted inhibitors for nuclear medicine applications
No full textBackground: The rising incidence rate of prostate cancer (PCa) has promoted the development of new diagnostic and therapeutic radiopharmaceuticals during the last decades. Promising im-provements have been achieved in clinical practice using prostate specific membrane antigen (PSMA) labeled agents, including specific antibodies and small molecular weight inhibitors. Focusing on molecular docking studies, this review aims to highlight the progress in the design of PSMA targeted agents for a potential use in nuclear medicine. Results: Although the first development of radiopharmaceuticals able to specifically recognize PSMA was exclusively oriented to macromolecule protein structure such as radiolabeled monoclonal antibodies and derivatives, the isolation of the crystal structure of PSMA served as the trigger for the synthesis and the further evaluation of a variety of low molecular weight inhibitors. Among the nuclear imaging probes and radiotherapeutics that have been developed and tested till today, labeled Glutamate-ureido inhibitors are the most prevalent PSMA-targeting agents for nuclear medicine applications. Conclusion: PSMA represents for researchers the most attractive target for the detection and treatment of patients affected by PCa using nuclear medicine modalities. [99mTc]MIP-1404 is considered the tracer of choice for SPECT imaging and [68Ga]PSMA-11 is the leading diagnostic for PET imaging by general consensus. [18F]DCFPyL and [18F]PSMA-1007 are clearly the emerging PET PSMA candidates for their great potential for a widespread commercial distribution. After paving the way with new imaging tools, academic and industrial R&Ds are now focusing on the development of PSMA inhibitors labeled with alpha or beta minus emitters for a theragnostic application
Utility of [11C]choline PET/CT in guiding lesion-targeted salvage therapies in patients with prostate cancer recurrence localized to a single lymph node at imaging: results from a pathologically validated series
No full textObjective: Positron emission tomography (PET)/computed tomography (CT) has been shown to be a valid tool in detecting lymph node (LN) metastases in men with biochemical recurrence after radical prostatectomy. We assessed its validity in detecting a single positive LN at pathologic examination in regard to an increasing interest in lesion-targeted salvage therapies. Methods and materials: We included 46 patients with biochemical recurrence after radical prostatectomy and a single positive spot at [11C]choline PET/CT who underwent pelvic or pelvic and retroperitoneal LN dissection. The ability of [11C]choline PET/CT in identifying the exact positive LN was assessed with the positive predictive value (PPV) in the overall population and according to androgen deprivation therapy, prostate-specific antigen value, and site of PET/CT positivity. Results: Overall, 30 patients (65%) had positive LNs at pathologic examination. Of these, only 16 (35%) had pathologically confirmed metastases in the same lymphatic region and 11 (24%) had involvement of 1 single LN. Conversely, 28 patients had positive LNs in other areas and 8 had no evidence of metastases. The overall PPV of PET/CT was 34.8% and 23.9% when exact concordance was defined according to the lymphatic landing site and single positive LN, respectively. The PPV ranged from 33.3% to 44.4% and from 17.9% to 28.6%, in men with and without androgen deprivation therapy, respectively. Conclusions: The PPV [11C]choline of PET/CT in correctly identifying patients with a single positive LN at salvage LN dissection is poor (24%). Therefore, extensive salvage treatment approaches are needed to maximize the chance of cure. © 2014 Elsevier Inc
Do we have to withdraw antiandrogenic therapy in prostate cancer patients before PET/CT with [11C]choline?
No full textDo we have to withdraw antiandrogenic therapy in prostate cancer patients before PET/CT with [11C]choline?
No full textRiluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins
No full textHuntington disease (HD) mutation increases gain-of-toxic functions contributing to glutamate-mediated excitotoxicity. Riluzole interferes with glutamatergic neurotransmission, thereby reducing excitotoxicity, enhancing neurite formation in damaged motoneurons and increasing serum concentrations of BDNF, a brain cortex neurotrophin protecting striatal neurons from degeneration. We investigated metabolic and volumetric differences in distinct brain areas between 11 riluzole-treated and 12 placebo-treated patients by MRI and (18)F-fluoro-2-deoxy-d-glucose (FDG) PET scanning, according to fully automated protocols. We also investigated the influence of riluzole on peripheral growth factor blood levels. Placebo-treated patients showed significantly greater proportional volume loss of grey matter and decrease in metabolic FDG uptake than patients treated with riluzole in all cortical areas (p < 0.05). The decreased rate of metabolic FDG uptake correlated with worsening clinical scores in placebo-treated patients, compared to those who were treated with riluzole. The progressive decrease in metabolic FDG uptake observed in the frontal, parietal and occipital cortex correlated linearly with the severity of motor scores calculated by Unified Huntington Disease Rating Scale (UHDRS-I) in placebo-treated patients. Similarly, the rate of metabolic changes in the frontal and temporal areas of the brain cortex correlated linearly with worsening behavioural scores calculated by UHDRS-III in the placebo-treated patients. Finally, BDNF and transforming growth factor beta-1 serum levels were significantly higher in patients treated with riluzole. The linear correlation between decreased metabolic FDG uptake and worsening clinical scores in the placebo-treated patients suggests that FDG-PET may be a valuable procedure to assess brain markers of HD
NUMBER OF POSITIVE SPOTS AT PET-CT SCAN PREDICTS CANCER SPECIFIC AND OVERALL SURVIVAL IN PATIENTS TREATED WITH SALVAGE LYMPH NODE DISSECTION FOR RECURRENCE AFTER RADICAL PROSTATECTOMY
No full textWeighted registration of123I-FP-CIT SPECT images improves accuracy of binding potential estimates in pathologically low striatal uptake
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