Abstract
Background: Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with clinically approved ligands for technetium complexation. Methods: The influence of synthesized IDA derivatives on plasma haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test), coagulation assay, Prothrombin Time and Activated Partial Tromboplastin Time. The effects of the tested compounds on erythrocytes were assessed using haemolysis assays, microscopy and flow cytometry studies. Results: Despite their significant influence on the kinetic parameters of the process of clot formation and fibrinolysis, the tested ligands, at potential diagnostic concentrations, did not alter the overall potential of clot formation and lysis (CLAUC). At potential diagnostic concentrations (0.4 μmol/mL) all the tested compounds showed no adverse effects on the membranes of RBCs (Red Blood Cells). Conclusion: IDA derivatives with methoxy substituents in aromatic ring, exert multidirectional effects on plasma haemostasis and should be considered safe as their significant impacts were mostly observed at 4 μmol/mL, which is about 10-fold higher than the theoretical plasma concentrations of these compounds.
Highlights
Any novel chemical substance or biomedical material must reach their biocompatibility before being put into clinical use
We found that five Iminodiacetic acid (IDA) derivatives, the ligands for technetium used in cholescintigraphy, exert multi-dimensional effects on the coagulation and fibrinolysis [15]
Taking into consideration the above-mentioned literature examples and the necessity to establish the biocompatibility of potential ligands for technetium complexation, the purpose of this study was to assess the effect of five novel iminodiacetic acid derivatives on plasma haemostasis by measuring the overall potential of clot formation and fibrinolysis and the kinetic parameters of these processes, and to draw the conclusion which group of iminodiacetic acid derivatives presents favourable properties regarding plasma haemostasis and effects on morphology of RBCs
Summary
Any novel chemical substance (e.g., drugs, drug carriers, contrast agents used for imaging) or biomedical material (e.g., implants, sutures, glues) must reach their biocompatibility before being put into clinical use. The typical way of administrating diagnostic agents (including both contrast agents (CAs) and radiopharmaceuticals) is intravenously. These compounds should only exert a minimum. Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with clinically approved ligands for technetium complexation. Conclusion: IDA derivatives with methoxy substituents in aromatic ring, exert multidirectional effects on plasma haemostasis and should be considered safe as their significant impacts were mostly observed at 4 μmol/mL, which is about 10-fold higher than the theoretical plasma concentrations of these compounds
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