Effect of amino acid infusion on potassium serum levels in neuroendocrine tumour patients treated with targeted radiopeptide therapy

Purpose: Administration of positively charged amino acids has been introduced to reduce the nephrotoxicity of targeted radiopeptide therapy (TRT). However, the amino acid solution may have side effects, including hyperkalaemia. The aim of this study was to evaluate the frequency and the magnitude of hyperkalaemia in neuroendocrine tumour (NET) patients undergoing TRT. Methods: Enrolled in the study were 31 patients with NET eligible for TRT with [90Y-DOTA(0),Tyr(3)]octreotide (90Y-DOTATOC). Their mean age was 54 ± 14years. Of these 31 patients, 21 (67%) were referred for the first treatment cycle, while 10 (33%) were referred for a subsequent therapy cycle. Patients were treated with therapeutic doses of 90Y-DOTATOC ranging from 7,030 to 35,520MBq. To inhibit tubular reabsorption of 90Y-DOTATOC, 1l of physiological saline solution containing 25g of arginine hydrochloride and 25g of lysine hydrochloride was given over 4h starting 1h before 90Y-DOTATOC injection. All patients underwent a standard biochemical blood analysis at baseline, and 4h and 24h after the beginning of the amino acid infusion. Results: ANOVA repeated measures showed a significant overall effect on K+ levels over time (F = 118.2, df = 2, P 0.05) to baseline K+ levels. Intravenous administration of 40mg furosemide 1h after the beginning of the amino acid infusion did not have a significant effect on K+ levels (P>0.05). No clinical characteristic was predictive for the increase in K+ levels (chi-squared test, P > 0.05). Conclusion: Hyperkalaemia is a frequent, potentially life-threatening side effect of basic amino acid infusion during TRT. K+ levels 4h after the beginning of the infusion should be monitored in patients at risk of complications, such as those with heart disease and those with risk factors for nephrotoxicit

Potentiometric measurement of urinary iodine concentration in patients with thyroid diseases with and without previous exposure to non-radioactive iodine

Background: Extensive application of measurement of urinary iodine concentration (UIC) in several benign and malignant thyroid diseases could profit by the availability of rapid and inexpensive measuring techniques. Aim of this study was to apply a simple and inexpensive commercially available potentiometric method for the quantification of UIC based on iodine-specific ion-selective electrodes (ISE) in patients with thyroid diseases. Methods: This retrospective study included patients with differentiated thyroid cancer (n=286) and patients with hyperthyroidism of different etiologies (n=203). Within the whole sample (n=489) 20 patients had previously (1 week-6 months) been exposed to iodine overload, either from contrast media (n=8) or amiodarone (n=12). Results: In patients not exposed to iodine, the histogram showed that the distribution of UIC violated normality. The peak of the curve occurred between 5.0 μmol/L and 6.0 μmol/L. Variability was sizeable (percent coefficient of variation, %CV: 66%, 95% confidence interval: 1.48-18.72 μmol/L). The group of exposed patients could be easily distinguished from not exposed patients (median UIC: 47.5 μmol/L vs. 5.42 μmol/L). UIC was significantly correlated to urinary creatinine concentration, but normalization to urinary creatinine increased the inter-subject variability of UIC (%CV=96% vs. 66%). In test-retest studies (n=25) the intra-class correlation coefficient was 0.73 for UIC, 0.82 for creatinine and 0.64 for the UIC: creatinine ratio. Conclusions: Iodine-specific ISE-based potentiometric methods can be successfully applied as an alternative to existing methods in patients with thyroid diseases. The promising characteristics of the method need to be confirmed in future larger prospective studies

Toward the discovery and development of PSMA targeted inhibitors for nuclear medicine applications

Background: 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

Targeted radiotherapy with radiolabeled somatostatin analogs

Targeted radiopeptide therapy with (90)Yttrium- or (177)Lutetium-labeled somatostatin analogs has been proven to improve significantly quality of life and survival in patients suffering from metastatic or unresectable neuroendocrine tumors (NETs). Roughly 25% of patients achieve partial remission; progression-free survival is estimated to be 30 to 40 months. A wide range of protocols using different somatostatin analogs, isotopes, injected activity per cycle of administration, and number of cycles are reported. More patient-based therapy protocols are under development, taking into consideration the complexity of NET cell biology, dosimetric issues, and the availability of different radiolabeled analogs. This article reviews the effectiveness and safety of the different protocols and discusses several clinical algorithms used in an attempt to optimize targeted radiopeptide therapy

Effect of amino acid infusion on potassium serum levels in neuroendocrine tumour patients treated with targeted radiopeptide therapy

Administration of positively charged amino acids has been introduced to reduce the nephrotoxicity of targeted radiopeptide therapy (TRT). However, the amino acid solution may have side effects, including hyperkalaemia. The aim of this study was to evaluate the frequency and the magnitude of hyperkalaemia in neuroendocrine tumour (NET) patients undergoing TRT

Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins

Huntington 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

11C-choline PET/CT predicts prostate cancer-specific survival in patients with biochemical failure during androgen-deprivation therapy

Several studies have shown that (11)C-choline PET/CT may be useful for restaging prostate cancer (PCa) patients with biochemical failure after radical prostatectomy. However, validation of (11)C-choline PET/CT findings scarcely relied on histologic findings, and prognostic implications of (11)C-choline PET/CT are currently unknown. The aim of this study was to assess whether (11)C-choline PET/CT predicts survival in PCa patients.; This retrospective study included 195 PCa patients treated with radical prostatectomy who underwent (11)C-choline PET/CT from December 1, 2004, to July 31, 2007, due to biochemical failure (prostate-specific antigen 0001). At multivariate analysis, statistical significance was obtained for (11)C-choline PET/CT (hazard ratio, 2.53; 95% CI, 1.41-4.53; P = 0.002), prostate-specific antigen (hazard ratio, 1.03; 95% CI, 1.00-1.05; P = 0.037), and Gleason score (<7: hazard ratio, 2.49; 95% CI, 1.25-4.95; P = 0.009). Patients with pathologic (11)C-choline uptake in the prostatic bed or in pelvic or retroperitoneal lymph nodes had longer PCa-specific survival (median, 12.1 y; 95% CI, 10.5-13.7 y) in comparison to patients with pathologic tracer uptake in the skeleton (median, 9.9 y; 95% CI, 6.8-13.1 y) (log-rank: χ(2) = 6.5, P = 0.010). Two internally validated nomograms predicted 10- and 15-y PCa-specific survival probability with an accuracy of 76% and 74%, respectively. In an ancillary analysis, we also showed that (11)C-choline PET/CT predicts PCa-specific survival after PET/CT, with similar statistical power.; (11)C-choline PET/CT predicts PCa-specific survival in PCa patients treated with radical prostatectomy who develop biochemical failure during androgen-deprivation therapy. If independent or multicenter confirmation of these findings is obtained, (11)C-choline PET/CT might be more widely used in the follow-up of PCa patients for tailoring salvage therapy