Résumé
Objective:To explore the relation of the radiochemical purity and in vivo imaging effect of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)- D-phe1-Tyr3-Thr8-octreotide (TATE) injection. Methods:High performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) methods were established to determine 68Ga-DOTATATE, 68Ga 3+ , 68Ga in colloidal form and 68Ga-DOTA- D-Phe1-Tyr3-Thr8-dethreonine-octreotide (heptapeptide) and to study the influence of precursor purity on radiochemical purity of labelled products. The uptake of 68Ga-DOTATATE injection with different radiochemical purities was investigated in nude mice bearing AR42J cells by microPET imaging and the tumor target/non-target (T/NT) value was calculated. One-way analysis of variance and Pearson correlation analysis were used to analyze the data. Results:The contents of 68Ga 3+ and 68Ga in colloidal form were not related with precursor purity ( r values: 0.385, 0.497, P values: 0.306, 0.137), while the content of 68Ga-DOTA-heptapeptide was positively related with the purity of DOTA-heptapeptide ( r=0.957, P<0.001). The radiochemical purities of 68Ga-DOTATATE injection were (87.0±2.3)%, (86.8±0.8)% and (94.0±3.1)% when the DOTATATE purities were 90.9%, 91.6% and 99.2%, respectively. The results of microPET imaging showed that the tumor uptake was positively related with the radiochemical purity of 68Ga-DOTATATE injection ( r=0.828, P<0.001), and the T/NT values of 68Ga-DOTATATE injection with radiochemical purities of 95.7%, 85.8%, 84.5% and 79.9% were 21.25±8.84, 8.50±1.51, 11.38±1.65 and 6.01±0.99, respectively ( F=11.48, P=0.001). Conclusion:The radiochemical purity of 68Ga-DOTATATE injection is impacted by the purity of labelled precursor and manufacturing processes and is related with the imaging effect in vivo.
Résumé
Abstract Objective: To compare an albumin-bound gadolinium chelate (gadofosveset trisodium) and an extracellular contrast agent (gadobenate dimeglumine), in terms of their effects on myocardial longitudinal (T1) relaxation time and partition coefficient. Materials and Methods: Study subjects underwent two imaging sessions for T1 mapping at 3 tesla with a modified look-locker inversion recovery (MOLLI) pulse sequence to obtain one pre-contrast T1 map and two post-contrast T1 maps (mean 15 and 21 min, respectively). The partition coefficient was calculated as ΔR1myocardium /ΔR1blood , where R1 is 1/T1. Results: A total of 252 myocardial and blood pool T1 values were obtained in 21 healthy subjects. After gadolinium administration, the myocardial T1 was longer for gadofosveset than for gadobenate, the mean difference between the two contrast agents being −7.6 ± 60 ms (p = 0.41). The inverse was true for the blood pool T1, which was longer for gadobenate than for gadofosveset, the mean difference being 56.5 ± 67 ms (p < 0.001). The partition coefficient (λ) was higher for gadobenate than gadofosveset (0.41 vs. 0.33), indicating slower blood pool washout for gadofosveset than for gadobenate. Conclusion: Myocardial T1 times did not differ significantly between gadobenate and gadofosveset. At typical clinical doses of the contrast agents, partition coefficients were significantly lower for the intravascular contrast agent than for the extravascular agent.
Resumo Objetivo: Avaliar o efeito da utilização de um agente de contraste intravascular baseado em gadolínio quelado a albumina (gadofosveset) no tempo T1 e no coeficiente de partição do miocárdio, quando comparado com um agente de contraste extravascular baseado no gadolínio não quelado a albumina (gadobenato). Materiais e Métodos: Os participantes do estudo foram submetidos a dois exames para aquisições do mapeamento T1 em aparelho de 3 tesla. Utilizando uma sequência de pulso modificada - modified look-locker inversion recovery (MOLLI) -, realizou-se uma etapa pré-contraste e duas etapas pós-contraste do mapa T1 (média de 15 e 21 minutos). O coeficiente de partição foi calculado como: ΔR1miocárdio /ΔR1sangue. Resultados: Um total de 252 valores de mapa T1 no miocárdio e no sangue foi obtido em 21 indivíduos saudáveis. Após a administração do meio de contraste, a diferença média do tempo T1 do miocárdio entre os agentes de contraste foi -7,6 ± 60 ms (p = 0,41) (isto é, gadobenato T1 < gadofosveset T1). Já no sangue, a diferença média de tempo T1 foi 56,5 ± 67 ms (p < 0,001) (isto é, gadobenato T1 > gadofosveset T1). O coeficiente de partição foi maior para o gadobenato (λ = 0,41) do que para o gadofosveset (λ = 0,33), refletindo uma eliminação mais lenta do gadofosveset em comparação com o gadobenato. Conclusão: Os tempos T1 do miocárdio não foram significativamente diferentes entre gadobenato e gadofosveset. Os coeficientes de partição foram significativamente mais baixos para o agente de contraste intravascular em comparação com o agente extravascular em doses clínicas típicas de cada contraste.
Résumé
Objective To investigate the preventive effect of Strontium ranelate on stress-absence induced osteoporo?sis in tail-suspended rat. Methods A total of 30 SD rats with average age of 6 month were randomly divided into 3 groups (n=10 in each group):Group A was normal control group while rats in group B and C were subjected to tail suspension test to establish stress absence models. Rats in group C were administered with Strontium ranelate [1 g/(kg·d)]. All rats were sacri?ficed 4 weeks later. Left femurs were harvested for bone mineral density (BMD) test and prepared for undecalcified tissue sec?tion and thereby bone histomorphometry assessment. Bone marrow from right femurs and tibias were cultured and induced to?wards osteogenic-differentiation. The expression levels of osteocalcin in the fourth-passage cultured bone marrow cells and in blood serum were detected separately. Results Rats in group B showed markedly decreased BMD comparing to those in group A and C(P<0.05). Trabecular volume (BV/TV), number (Tb.N) and thickness (Tb.Th) in group B were lower than those in group A and C;erosion percentage (Er.Pm) and osteoclast number (Oc.N) in group B and C were higher than those in group A;comparing to those in group B, bone formation rate (BFR/BV), labeled percentage (L.Pm), were higher in group C, coupled with decreased Er.Pm and Oc.N(P<0.05). mRNA expression levels of OCN in group B and C were higher than those of group A. But its level in plasma were lower in group B than those in group A and C(P<0.05). Conclusion Tail suspension could induce osteosporosis. Strontium ranelate prevent bone loss in stress-absence osteoporosis in rat induced by tail-suspension for 4 weeks, which might be partially through upregulating the expression of OCN, thereby promoting bone formation.
Résumé
Nodular regenerative hyperplasia (NRH) consists in diffuse transformation of the hepatic parenchyma into small regenerative nodules without fibrosis, secondary to vascular occlusion and flow alterations. This gives a nodular appearance to theliver, as there is atrophy and compensatory hypertrophy of hepatocytes. We reporta 69-year-old male who suffered of colon cancer and was treated with Oxaliplatin (OX) and Bevacizumab (B). During treatment with B the patient presented a partial thrombosis of the portal vein, that one year later became permeable. Esophageal varices were found in an upper digestive endoscopy. Hepatic tests were normal. Aliver biopsy was performed and informed nodular regenerative hyperplasia. Thus, the different factors that could explain this pathology are analyzed. B, a monoclonal antibody against vascular endothelial growth factor, reduces the anti-apoptotic, anti-inflammatory and survival effects produced by this factor, affecting the vascular protection of the endothelial cell. On the other hand, OX activates metalloproteinasesand depletes sinusoidal glutathione producing sinusoidal lesions. Thus, (OX) would be associated with sinusoidal obstruction and NRH sporadically. It is important to discuss the possible etiologic factors that can cause NRH reviewing the hepatotoxic effects caused by both drugs.