Impact of 68GA-PSMA PET / CT on treatment of patients with recurrent / metastatic high risk prostate cancer - a multicenter study

ABSTRACT Purpose: The purpose of our study was to evaluate the clinical impact of 68Ga-PSMA PET / CT in the setting of biochemical recurrence of prostate cancer. Materials and Methods: We retrospectively evaluated 125 prostate cancer patients submitted to the 68Ga-PSMA PET / CT due to biochemical recurrence. The parameters age, Gleason score, PSA levels, and the highest SUVmax were correlated to potential treatment changes. The highest SUVmax values were correlated with age and Gleason score. The median follow-up time was 24 months. Results: 68Ga-PSMA PET / CT led to a treatment change in 66 / 104 (63.4%) patients (twenty-one patients were lost to follow-up). There was a significant change of treatment plan in patients with a higher Gleason score (P = 0.0233), higher SUVmax (p = 0.0306) and higher PSA levels (P < 0.0001; median PSA = 2.55 ng / mL). Conclusion: 68Ga-PSMA PET / CT in prostate cancer patients with biochemical recurrence has a high impact in patient management.

Use of EDTA in the treatment of local tissue damage caused by the Bothrops alternatus venom / Utilização do EDTA no tratamento da lesão tecidual local causado pelo veneno de Bothrops alternatus

Twelve adult rabbits were distributed in three groups and received on the femoral biceps region, via intradermal injection (ID), 25µg of Bothrops alternatus venom dissolved in NaCl 0.9% and diluted in 0.25mL of phosphate buffered saline (PBS). Thirty minutes later, the group G1 received 0.25mL of phosphate buffered saline (PBS) ID while to G2 and G3 25mg of ethylenediamine tetraacetic acid (EDTA) dissolved in 0.25mL of PBS were administered via intramuscular (IM) and intravenous (IV) injection, respectively. Evaluations included local lesion and blood profile of all animals, before (time zero) and at 1, 2, 3, 4, 5, 6, 12, 18 and 24h after venom administration. All animal treated with PBS (G1) and EDTA IV (G3) presented increase of nociceptive stimuli at the site of inoculation of the venom, followed by moderate edema that persisted for 24h. Animals treated with IM EDTA (G2) only manifested increase of nociceptive stimuli at the site of injection 1h after treatment with discrete local edema between 12 and 24h. In relation to the local hemorrhagic halo no differences were found amongst the studied groups. Blood profile revealed significant decrease of segmented neutrophils in all groups. There was also increase in triglycerides and decrease in total protein and albumin in all groups. The local lesion was not altered by the treatments.(AU)

Doze coelhos adultos, distribuídos em três grupos, receberam, na região de bíceps femoral, por via intradérmica (ID), 25µg de veneno de Bothrops alternatus, dissolvidos em NaCl 09%, diluído em 0,25mL de tampão salina fosfato (PBS). Trinta minutos após o desafio, o grupo G1 recebeu 0,25mL de (PBS) ID, e os grupos G2 e G3 receberam 25mg de ácido etilenodiamino tetra-acético (EDTA), dissolvidos em mL de PBS por via intramuscular (IM) e intravenosa (IV), respectivamente. Foram avaliados lesão local e perfil sanguíneo de todos os animais, antes - tempo zero, e à uma, às duas, três, quatro, cinco, seis, 12, 18 e 24 horas após a injeção do veneno. Tanto os animais tratados com PBS (G1) como os animais tratados com EDTA IV (G3) apresentaram aumento do estímulo nociceptivo no local da administração do veneno, seguido por moderado edema, que perdurou por 24h. Os animais tratados com EDTA IM (G2) somente manifestaram aumento do estímulo nociceptivo local uma hora após tratamento e discreto edema local entre 12 e 24 horas. Em relação ao halo hemorrágico, não houve diferença entre os três grupos estudados. No perfil hematológico, observou-se diminuição significativa dos neutrófilos segmentados nos três grupos estudados. Da mesma forma, houve aumento dos triglicerídeos e diminuição da proteína total e albumina em todos os grupos. Conclui-se que a lesão local não foi alterada pelos tratamentos.(AU)

Synthesis and preliminary evaluation of a new[99m]Tc labeled substance P analogue as a potential tumor imaging agent

Neurokinin 1 receptors [NK[1]R] are overexpressed on several types of important human cancer cells. Substance P [SP] is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK[1]R positive tumors.[6-hydrazinopyridine-3-carboxylic acid [HYNIC]-Tyr[8]-Met[O][11]-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N,N-diacetic acid [EDDA]and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity [>99%] and radiolabeled with [99m]Tc at high specific activities [84-112GBq/ micro mol] with an acceptable labeling yield [>95%]. The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 +/- 0.22% with the ratio of 60.21 +/- 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 +/- 0.43 nM and Bmax of 128925 +/- 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram [%ID/g] for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK[1]R positive primary or secondary tumors

Relation between Calcium Loss and Its Effect on Microhardness of Root Canal Dentin Following Treatment With 17% Ethylene Diamine Tetraacetic Acid(EDTA) at Different Time Intervals: An Ex-Vivo Study.

Decalcification and its effect on microhardness of root canal dentin by an aqueous solution of 17% EDTA at different time intervals were studied.Single rooted forty extracted human premolar teeth after adequate processing and embedded with acrylic resin were randomly divided into 8 groups based on different time intervals. Each sample group was assessed for Ca²⁺ release into the test solution by Atomic Absorption Spectrophotometer, respectively and then were subjected for microhardness testing.17% EDTA and 0.9% Saline, test solutions were used; EDTA was adjusted to 7.5 pH. Data analysis was done by One Way analysis of variance (ANOVA) and the comparison of means was done by using Tukey’s multiple comparison tests. The decalcifying activity of 17% EDTA solution was time dependent and increased immersion time showing very high significant influence on the amount of calcium extracted (<strong>F=154.304, p). The reduction in microhardness for 17% EDTA solution was time dependent and increased immersion time showing very high significant decrease in the microhardness among the different time intervals tested (<strong>F=249.925, p < 0.0005</strong>).Effect of 17 % EDTA solution as root canal irrigant is time dependent as evidenced by dentin microhardness reduction.

An Incidentally Found Inflamed Uterine Myoma Causing Low Abdominal Pain, Using Tc-99m-Tektrotyd Single Photon Emission Computed Tomography-CT Hybrid Imaging

We report the case of a 50-year-old woman presented with a history of right hemicolectomy due to an ileocecal neuroendocrine tumor and left breast metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal pain, single photon emission computed tomography-computer tomography (SPECT-CT) was performed. There were no signs of recurrence on the SPECT-CT scan, but the patient was incidentally found to have an inflamed intramural myoma. We believe that the slightly elevated chromogranin A-level was caused by the hypertension that the patient presented. In the clinical context, this is a report of an inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc-EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging.

Synthesis and evaluation of a new radiolabeled bombesin analogue for diagnosis of GRP receptor expressing tumors

Bombesin [BN], a 14-amino acid neuropeptide, shows high affinity for the human GRP [gastrin releasing peptide] receptors, which are overexpressed by a variety of cancers, including prostate, breast, pancreas, gastrointestinal, and small cell lung cancer. Aim was to prepare [6-hydrazinopyridine-3-carboxylic acid [HYNIC[0], D-Tyr[6], D-Trp[8]] - BN [6-14] NH[2] that could be easily labeled with[99m]Tc and evaluation of its potential as an imaging agent. Synthesis of the peptide amide was carried out onto Rink Amide MB HA [4-Methylbenzhydrylamine] resin. A bifunctional chelating agent [BFCA] was attached to the N terminal peptide in solid-phase. [99m]Tc labeling was performed by addition of sodium pertechnetate to solution that include [HYNIC[0], D-Tyr[6], D-Trp[8]] Bombesin [6-14] NH[2], tricine, ethylenediamine-N,N'-diaeetic acid [EDDA] and SnCl[2]. Radiochemical evaluation was carried out by reverse phase high-performance liquid chromatography [HPLC] and instant thin layer chromatography [ITLC]. In- vitro internalization was tested using human prostate cancer cells [PC-3] with blocked and non-blocked receptors. Biodistribution was determined in rats. [99m]Tc/tricine/EDDA-HYNIC[0], D-Tyr[6], D-Trp[8]] bombesin [6-14] NH[2] was obtained with radiochemical purities >98%. Results of in-vitro studies demonstrated a high stability in serum and suitable internalization. Biodistribution data showed a rapid blood clearance, with renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas. In this study, labeling of this novel conjugate with [99m] Tc easily was performed using coligand. The prepared [99m]Tc-HYNIC-BN conjugate has promising characteristics for the diagnosis of malignant tumors

A scanning electron microscopic evaluation of different root canal irrigation regimens / Avaliação por microscopia eletrônica de varredura de diferentes regimes irrigantes no canal radicular

The purpose of this study was to assess the effectiveness of endodontic irrigants in removing the smear layer from instrumented root canal walls using Scanning Electron Microscopy (SEM). The endodontic irrigants used were: 1 percent sodium hypochlorite (NaOCl); 1 percent NaOCl mixed to 17 percent EDTAC; 2 percent chlorhexidine gel; and Ricinus communis gel. Photomicrographs of the middle and apical thirds were evaluated with the aid of the Fotoscore - v. 2.0 software. The results indicated that the mixture of sodium hypochlorite and EDTAC completely removed the smear layer from dentinal walls. The other endodontic irrigants were not as efficient in cleansing the root canals.

A proposta deste estudo foi avaliar, por meio de microscopia eletrônica de varredura (MEV), a efetividade dos irrigantes endodônticos na remoção da "smear layer" das paredes dos canais radiculares instrumentados. Os irrigantes endodônticos utilizados foram: solução de hipoclorito de sódio a 1 por cento; solução de hipoclorito de sódio a 1 por cento misturado ao EDTAC a 17 por cento, gel de clorexidina a 2 por cento e gel de Ricinus communis. Fotomicrografias dos terços médio e apical foram avaliadas com o auxílio do software Fotoscore - versão 2.0. Os resultados indicaram que a mistura da solução de hipoclorito de sódio e EDTAC removeu eficientemente a "smear layer" das paredes dentinárias. Os demais irrigantes endodônticos não foram tão eficientes na limpeza dos canais.

Smear layer removal and chelated calcium ion quantification of three irrigating solutions

The purpose of this study was to evaluate, by scanning electron microscopy (SEM), smear layer removal and quantify, by atomic absorption spectrophotometry, the amount of calcium ion present in the chelating solutions after their use. Sixteen extracted canines were instrumented using the step-back technique and were assigned to 3 groups according to the irrigating solution used: G1: 1 mL 17 percent EDTAC between each file; G2: 1 mL 17 percent CDTA; G3: 1 mL 17 percent EGTA. The solutions were collected after use. The teeth were cleaved longitudinally, evaluated under SEM and assessed for smear layer by blinded examiners and scored from 1 to 4. In order to quantify calcium ion release, the collected solutions were examined by atomic absorption spectrophotometry. Freidman's test was used for statistical analysis of SEM values and showed that canals irrigated with 17 percent EDTAC and 17 percent CDTA had significantly less smear layer throughout the canals than 17 percent EGTA (p<0.01). For analysis of the collected solutions, Tukey's test was used and showed that EDTAC and CDTA had a greater amount of calcium ions (22.8±7.54 and 60.6±20.67 æg/mL, respectively) compared to EGTA (70.5±14.2 æg/mL) (p<0.01). The association both methodologies may contribute to the understanding of how these solutions act in the root canal.

O objetivo do presente estudo foi avaliar a remoção de smear layer por meio da microscopia eletrônica de varredura (MEV) e quantificar a liberação de íons cálcio resultante da irrigação com as soluções quelantes estudadas, por meio da espectrofotometria de absorção atômica. Dezesseis caninos extraídos foram instrumentados com a técnica step-back e divididos em 3 grupos de acordo com a solução irrigadora utilizada: G1: 1 mL de EDTAC a 17 por cento entre cada lima; G2: CDTA a 17 por cento; e G3: EGTA a 17 por cento. As soluções foram coletadas após o uso. Os dentes foram secionados longitudinalmente e as raízes examinadas por MEV para verificação de smear layer nos terços por meio de escores (variando de 1 a 4), e avaliadas por três examinadores calibrados "cegos". Para quantificar a liberação de íons cálcio, as soluções coletadas foram avaliadas por espectrofotometria de absorção atômica. Com relação ao smear layer, o teste de Friedman evidenciou diferença estatisticamente significante (p<0,01) comparando-se o EGTA 17 por cento ao EDTAC 17 por cento e ao CDTA 17 por cento, sendo que os canais irrigados com estas duas soluções apresentaram menor quantidade de smear layer que aqueles irrigados com EGTA. As soluções de EDTAC 17 por cento (70,5±14,2 æg/mL Ca) e CDTA 17 por cento (60,6±20,67 æg/mL Ca) apresentaram maiores quantidades de íons cálcio (p<0,01) quando comparadas ao EGTA 17 por cento (22,8±7,54 æg/mL Ca). Desta forma, pode-se concluir que a associação destas metodologias pode contribuir para o entendimento da ação das soluções quelantes no interior dos canais radiculares.

Demineralization effect of EDTA, EGTA, CDTA and citric acid on root dentin: a comparative study / Efeito do EDTA, EGTA, CDTA e ácido cítrico na desmineralização da dentina radicular: estudo comparativo

Este trabalho teve como objetivo comparar o efeito desmineralizante do EDTA (pH 7,4), EGTA (pH 7,4), CDTA (pH 7,4), ácido cítrico (pH 1,0 e 7,4) e da solução salina (controle) sobre a dentina radicular. Todas as soluções teste foram preparadas na concentração de 1%. Quarenta e oito dentes unirradiculares recém-extraídos foram utilizados neste experimento. Após a instrumentação dos canais radiculares pela técnica "step-back", as raízes foram aleatoriamente divididas em 6 grupos experimentais (n = 8) de acordo com a solução teste utilizada na irrigação final. Em cada grupo, 30 µL da solução teste foram pipetados no interior de cada canal radicular e mantidos estáveis por 5 minutos. Decorrido esse período, 15 µL da solução foram removidos do canal e depositados em frasco contendo 5 mL de água deionizada. A concentração de Ca2+ (µg/mL) extraída dos espécimes foi determinada pela espectrometria de absorção de massa (ICP-AES); e os dados foram submetidos à análise estatística pelos testes de Kruskal-Wallis e de mediana de Mood. O ácido cítrico em pH 1,0 foi a solução mais efetiva na remoção de Ca2+ comparativamente às demais soluções-teste (p < 0,05). Nenhuma diferença estatística foi observada entre a ação do EDTA e a do EGTA. Ambos os quelantes removeram significantemente mais Ca2+ que o CDTA e o ácido cítrico em pH 7,4 (p < 0,05). Não houve diferença significante entre ácido cítrico em pH 7,4 e solução salina (p > 0,05). Os resultados deste estudo indicam que o ácido cítrico em solução de pH 1,0 apresenta-se como uma boa opção para remover a "smear layer" e facilitar o preparo biomecânico do sistema de canal radicular.

Gadobenate Dimeglumine as an Intrabiliary Contrast Agent: Comparison with Mangafodipir Trisodium with Respect to Non-dilated Biliary Tree Depiction

OBJECTIVE: To compare the efficacy of Mangafodipir trisodium (Mn-DPDP) -enhanced MR cholangiogrphy (MRC) and Gadobenate dimeglumine (Gd-BOPTA) -enhanced MRC in visualizing a non-dilated biliary system. MATERIALS AND METHODS: Eighty-eight healthy liver donor candidates underwent contrast-enhanced T1-weighted MRC. Mn-DPDP and Gd-BOPTA was used in 36 and 52 patients, respectively. Two radiologists reviewed the MR images and rated the visualization of the common duct, the right and left hepatic ducts, and the second-order branches using a 4-point scale. The contrast-to-noise ratio (CNR) of the common duct to the liver in the two groups was also compared. RESULTS: Mn-DPDP MRC and Gd-BOPTA MRC both showed similar visualization grades in the common duct (p = .380, Mann-Whitney U test). In the case of the proximal bile ducts, the median visualization grade was significantly higher with Gd-BOPTA MRC than with Mn-DPDP MRC (right hepatic duct: p = 0.016, left hepatic duct: p = 0.014, right secondary order branches: p = 0.006, left secondary order branches, p = 0.003). The common duct-to-liver CNR of the Gd-BOPTA MRC group was significantly higher (38.90+/-24.50) than that of the Mn-DPDP MRC group (24.14+/-17.98) (p = .003, Student's t test). CONCLUSION: Gd-BOPTA, as a biliary contrast agent, is a potential substitute for Mn-DPDP.

Evaluation of the effect of EDTA, EGTA and CDTA on dentin adhesiveness and microleakage with different root canal sealers

The effect of chelating solutions EDTA, EGTA and CDTA on human dentin adhesiveness and microleakage with 4 sealers (Sealer 26, Sealapex, N-Rickert and Endofill) was evaluated in vitro. Whether or not there was a mathematical correlation between the tests of adhesiveness and microleakage was also evaluated. A total of eighty maxillary and mandibular molars were used to test adhesiveness. After wearing of the occlusal surface to obtain a flat surface, the sealer was placed with an aluminum cylinder (10 mm x 6 mm). Adhesiveness was evaluated with a 4444 Instron universal testing machine. Microleakage was evaluated in 160 maxillary canines after root canal instrumentation, obturation and clearing. The penetration of India ink in the apical region was measured with a measurescope. The teeth were divided into 4 groups: group 1, distilled water, group 2, EDTA; group 3, EGTA; group 4, CDTA. Sealer 26 and EDTA had the best results (p<0.01) for adhesiveness and microleakage. There was no correlation between the test for adhesiveness and microleakage.