Parkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to alteration of the integrity of dopaminergic transporters (DATs). In recent years, some radiopharmaceuticals have been used in the clinic to evaluate the integrity of DATs. These include tropane derivatives such as radiolabeled β-CIT and FP-CIT with iodine-123 (123I), and TRODAT-1 with metastable technetium-99 (99mTc). Radiolabeling of β-CIT with radioactive iodine is based on electrophilic radioiodination using oxidizing agents, such as Chloramine T or Iodo-Gen®. For the first time, the present work performed a comparative study of the radiolabeling of β-CIT with iodine-131 (131I), using either Chloramine T or Iodo-Gen® as oxidizing agents, in order to improve the radiolabeling process of β-CIT and to choose the most advantageous oxidizing agent to be used in nuclear medicine. Both radiolabeling methods were similar and resulted in high radiochemical yield (> 95%), with suitable 131I-β-CIT stability up to 72 h. Although Chloramine T is a strong oxidizing agent, it was as effective as Iodo-Gen® for β-CIT radiolabeling with 131I, with the advantage of briefer reaction time and solubility in aqueous medium.

Individual therapeutic monitoring of busulfan (BU) minimizes its toxicity and improves the therapeutic outcomes during hematopoietic stem cell transplantation (HSCT). For individual dose adjustment, several blood collections are performed that are uncomfortable for patients. The aim of this pilot study was to validate a laboratory method for quantification of BU in saliva and to present the results obtained using this protocol in HSCT patients. We performed analyses of selectivity, precision and accuracy of saliva with standard concentrations of BU using ultra-high-performance liquid chromatography with diode array detection. We also determined salivary and plasmatic concentrations of BU in six HSCT patients. Saliva exhibited excellent selectivity, precision and accuracy for quantification of BU. In the patient samples, significant correlations were noted between plasmatic and salivary concentrations of BU (r=0.97, P<0.001 in the test dose; r=0.93, P<0.001 in the adjusted dose). Passing &Bablok regression revealed good agreement between the two methods (R=0.956 for test dose; R=0.927 for adjusted dose). In conclusion, the saliva is safe for laboratory BU measurement. The good agreement with plasma encourages further clinical studies using saliva for BU therapeutic monitoring.

Radiopharmaceuticals are compounds, with no pharmacological action, which have a radioisotope in their composition and are used in Nuclear Medicine for diagnosis and therapy of several diseases. In this work, the development and validation of an analytical method for 99m Tc-HSA, 99m Tc-EC, 99m Tc-ECD and 99m Tc-Sestamibi radiopharmaceuticals and for some raw materials were carried out by high performance liquid chromatography (HPLC). The analyses were performed in a Shimadzu HPLC equipment, LC-20AT Prominence model. Some impurities were identified by the addition of a reference standard substance. Validation of the method was carried out according to the criteria defined in RE n. 899/2003 of the National Sanitary Agency (ANVISA). The results for robustness of the method showed that it is necessary to control flow rate conditions, sample volume, pH of the mobile phase and temperature of the oven. The analytical curves were linear in the concentration ranges, with linear correlation coefficients (r 2) above 0.9995. The results for precision, accuracy and recovery showed values in the range of 0.07-4.78%, 95.38-106.50% and 94.40-100.95%, respectively. The detection limits (DL) and quantification limits (QL) varied from 0.27 to 5.77 µg mL-1 and 0.90 to 19.23 µg mL-1 , respectively. The values for HAS, EC, ECD and MIBI in the lyophilized reagents (LR) were 8.95; 0.485; 0.986 and 0.974 mg L-1 , respectively. The mean radiochemical purity for 99m Tc-HSA, 99m Tc-EC, 99m Tc-ECD and 99m Tc-Sestamibi was (97.28 ± 0.09)%, (98.96 ± 0.03)%, (98.96 ± 0.03)% and (98.07 ± 0.01)%, respectively. All the parameters recommended by ANVISA were evaluated and the results are below the established limits. Página FIGURA-Gerador de 99 Mo/ 99m Tc. 6 FIGURA 2-Diagrama do decaimento do 99 Mo a 99m Tc. 6 FIGURA 3-Esquema das reações para obtenção dos radiofármacos de 99m Tc 8 FIGURA 4-Estrutura quaternária do SAH com os resíduos de cisteína e triptofano em destaque. 9 FIGURA 5-Esquema simplificado das etapas de síntese do EC. (I) ácido Ltiazolidino-4-carboxílico, (II) EC. FIGURA 6-Estrutura de L,L-EC-99m Tc. FIGURA 7-Estrutura molecular de L,L-ECD-99m Tc. FIGURA 8-(A) Estrutura molecular do MIBI e (B) Estrutura molecular do Sestamibi-99m Tc FIGURA 9-Esquema simplificado de um sistema cromatográfico para CLAE. FIGURA 10-Cromatografia de exclusão molecular. (A) Aplicação da amostra. (B) Interação da amostra com os poros da fase estacionária. (C) Separação das moléculas da amostra de acordo a massa molecular. FIGURA 11-Princípio da cromatografia de par de íons. O pareador iônico adicionado à fase móvel se liga à fase estacionária apolar. Os grupos sulfonatos negativos ficam expostos na fase estacionária e interagem com os íons da amostra. FIGURA 12-Princípio da cromatografia planar. (A) aplicação da amostra; (B) inserção da placa em uma cuba com a fase móvel e (C) separação dos analitos. FIGURA 13-Fluxograma das fases envolvidas no processo de validação de um método analítico. FIGURA 14-Fluxograma das fases de marcação dos RL com 99m Tc.

The aim of this work was to develop a selective method for quantification of Sn(II) and Sn(IV) in dimercaptosuccinic acid (DMSA), ethylcysteinate dimer (ECD), methylenediphosphonic acid (MDP), and pyrophosphate radiopharmaceutical cold kits by differential pulse polarography. Methods: A dripping mercury electrode 150 polarographic/stripping analyzer with a conventional 3-electrode configuration was used with 3 M H 2 SO 4 and 3 M HCl supporting electrolytes for Sn(II) and Sn(IV), respectively. The polarographic analysis was performed using a 1-s drop time, 50-mVÁs 21 scan rate, 250-mV pulse amplitude, 40-ms pulse time, and 10-mV step amplitude. To quantify Sn(IV), oxidation of Sn(II) by H 2 O 2 was performed. The calibration curves for Sn (II) and Sn(IV) were obtained in the range of 0-10 mgÁmL 21 . Results: The analytic curves for Sn(II) in 3 M H 2 SO 4 and Sn(IV) in 3 M HCl were represented by the following equations: i (mA) 5 0.098 [Sn(II)] 1 0.018 (r 2 5 0.998) and i (mA) 5 0.092 [Sn(IV)] 1 0.016 (r 2 5 0.998), respectively. The detection limits were 0.21 mgÁmL 21 for Sn(II) and 0.15 mgÁmL 21 for Sn(IV). In DMSA, ECD, MDP, and pyrophosphate, 90.0%, 64.9%, 93.2%, and 87.5%, respectively, of the tin was present as Sn(II). In this work, selective determination of Sn(II) and Sn(IV) was achieved using 2 supporting electrolytes (H 2 SO 4 and HCl). In 3 M H 2 SO 4 , only Sn(II) produced a polarographic wave with the maximum current in 2370 mV. Under the same conditions, no current could be determined for Sn(IV). In 3 M HCl, Sn(II) and Sn(IV) were electroactive and the maximum currents of the 2 waves appeared in 2250 and 2470 mV. No other components of the lyophilized reagents had any influence. Conclusion: The developed polarographic method was adequate to quantify Sn(II) and Sn(IV) in DMSA, ECD, MDP, and pyrophosphate cold kits. Radi opharmaceutical cold kits for labeling with 99m Tc contain Sn(II) for reduction of technetium to lower oxidation states that are chemically reactive to specific ligands. Besides these ligands, the cold kits usually contain stannous chloride (SnCl 2 ) and different additives (complexing agents, antioxidants, and buffers). The amount of stannous ions varies (0.03-1.5 mg of SnCl 2 ), although a minimum concentration must be present to guarantee the lyophilized reagent shelf life and to allow efficient labeling with 99m Tc (1).Depending on the medium composition, Sn(II) ions in low-concentration solutions (,2.0Á10 24 M) are oxidized, and the formation of basic complexes takes place above pH 2.00 (2,3). The quantitative determination of Sn(II) in radiopharmaceutical cold kits is an important aspect of quality control, and the analytic method must be accurate even in the presence of Sn(IV) ions (4).Such techniques as colorimetry, titrimetry, spectrophotometry, voltammetry, and polarography have been described in the literature for Sn(II) determination in cold kits (5-12).Zimmer et al. studied the formation of a red porphyrin complex in the presence of Sn(II) ions using a colorimetric method....

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