Subject(s)
Anastomotic Leak/diagnostic imaging , Bile Duct Diseases/diagnostic imaging , Bile Ducts/diagnostic imaging , Biliary Atresia/surgery , Contrast Media/administration & dosage , Portoenterostomy, Hepatic/adverse effects , Anastomotic Leak/etiology , Anastomotic Leak/metabolism , Anastomotic Leak/physiopathology , Bile Duct Diseases/etiology , Bile Duct Diseases/metabolism , Bile Duct Diseases/physiopathology , Bile Ducts/metabolism , Bile Ducts/surgery , Biliary Tract/diagnostic imaging , Biliary Tract/metabolism , Contrast Media/pharmacokinetics , Extravasation of Diagnostic and Therapeutic Materials/diagnostic imaging , Extravasation of Diagnostic and Therapeutic Materials/etiology , Extravasation of Diagnostic and Therapeutic Materials/metabolism , Female , Gadolinium DTPA/administration & dosage , Gadolinium DTPA/pharmacokinetics , Humans , Imino Acids/administration & dosage , Infant , Ligaments/diagnostic imaging , Ligaments/metabolism , Liver/diagnostic imaging , Liver/metabolism , Magnetic Resonance Imaging , Tissue DistributionABSTRACT
The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to ß-neurotoxins (ß-NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main ß-NTx of M. fulvius venom. ß-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA) and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%-78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50) and PLA2 activity of bioconjugated ß-NTx decreased 3 and 2.5 times, respectively, in comparison with native ß-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of ß-NTx-DTPA-(67)Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with (67)Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of ß-NTx-DTPA-(67)Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of ß-NTx-DTPA-(67)Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.
Subject(s)
Elapid Venoms/chemistry , Gadolinium DTPA/pharmacokinetics , Lymphatic System/metabolism , Neurotoxins/pharmacokinetics , Animals , Elapidae , Gadolinium DTPA/chemistry , Lethal Dose 50 , Male , Mice , Molecular Imaging , Neurotoxins/chemistry , Neurotoxins/toxicity , Rats, Wistar , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/pharmacokinetics , Single Photon Emission Computed Tomography Computed Tomography , Tissue DistributionABSTRACT
The hepatobiliary-specific contrast medium (gadoxetic acid - Primovist®) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Contrast Media , Gadolinium DTPA , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging/methods , Animals , Carcinoma, Hepatocellular/pathology , Chronic Disease , Contrast Media/pharmacokinetics , Diagnosis, Differential , Gadolinium DTPA/pharmacokinetics , Humans , Image Enhancement/methods , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Organ Specificity , Organic Anion Transporters , Sensitivity and SpecificityABSTRACT
ABSTRACT The hepatobiliary-specific contrast medium (gadoxetic acid – Primovist®) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis.
RESUMO O contraste hepato-específico (ácido gadoxético – Primovist®) tem como utilidade principal melhorar a detecção e a caracterização de lesões hepáticas focais, por exemplo, em hepatopatas crônicos com suspeita de hepatocarcinoma. Por apresentar captação seletiva por hepatócitos funcionantes na fase hepatobiliar tardia, auxilia na detecção de hepatocarcinomas típicos – a maioria dos quais apresentando hipossinal nessa fase. Essa característica de imagem também auxilia na diferenciação entre nódulos regenerativos/ displásicos e hepatocarcinomas precoces (com mais de 90% de acurácia), e entre hepatocarcinomas hipervascularizados e focos de pseudorrealce arterial. Perspectivas futuras promissoras incluem sua utilização na quantificação de função e de fibrose hepáticas.
Subject(s)
Animals , Humans , Contrast Media , Carcinoma, Hepatocellular/diagnosis , Gadolinium DTPA , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging/methods , Chronic Disease , Carcinoma, Hepatocellular/pathology , Contrast Media/pharmacokinetics , Diagnosis, Differential , Gadolinium DTPA/pharmacokinetics , Image Enhancement/methods , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Organ Specificity , Organic Anion Transporters , Sensitivity and SpecificityABSTRACT
PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the Gd-DTPA-BMA complex were prepared and radiolabeled by neutron activation. The radiolabeled liposomes presented significant in vitro cytotoxic activity against Ehrlich tumor cells when compared with controls. The biodistribution profile of these liposomes and free (159)Gd-DTPA-BMA were studied in mice bearing a previously-developed solid Ehrlich tumor. The results demonstrated an important uptake of the formulations by the tumor tissue, with a tissue/blood partition coefficient (Kp) 3.88 and 14.16 times higher than that of the free complex for pH-sensitive PEG-coated and PEG-folate-coated liposomes containing the (159)Gd-DTPA-BMA complex, respectively. Both formulations accumulated in the liver and spleen, thereby revealing some difficulty in escaping the action of the MPS cells. The formulation without folate presented a lower renal uptake, which is desirable in patients with chronic renal failure due to the potential risk of nephrogenic systemic fibrosis (NFS). The scintigraphic study revealed that the target/non-target ratio is always greater than three for pH-sensitive PEG-coated liposome formulations and above nine for pH-sensitive PEG-folate-coated liposome formulations. The results obtained in this study demonstrated that the formulations employed can be considered to be a potential alternative for the treatment of cancer, including patients with chronic renal failure.