Browsing by Subject "SPECT/CT"
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(2014)Many drugs are known to bind to melanin, a complex pigment polymer found in several human tissues. Melanin can act as a natural depot by prolonging the effect of the drug and reducing its toxicity. Since it is highly concentrated in the posterior part of the eye, pigment targeted long-acting drug delivery systems are proposed as an option in ocular diseases. In systemic drug delivery, pigment targeted drugs can potentially distribute to any melanin containing tissue. Therefore, the literature review of the thesis concentrates on the characteristics of melanin and melanosomes, drug binding property and melanin distribution in humans and other species. The main objective of the exploratory part was to determine if melanin binding can be studied with SPECT/CT (single photon emission computed tomography / computed tomography) imaging method. Two different melanin binding drugs, chloroquine and nadolol, were selected and labeled with iodine and radioactive iodine (123I). Equilibrium melanin binding of iodinated and non-iodinated drugs was studied in vitro in order to find out if iodination affects to the binding. Melanin binding was studied in vitro also with non-binding reference salicylic acid, I2-salicylic acid and salbutamol. Finally, melanin binding of 123I-choloroquine and 123I-nadolol was studied with SPECT/CT (NanoSPECT/CT, Bioscan Inc., USA) by comparing distribution kinetics between pigmented and albino rat. Drugs were administered intravenously to the tail vena and the distribution was followed in several time points, up to 24 h. Based on in vitro study, iodination increases melanin binding of hydrophilic drugs, nadolol and salicylic acid, significantly. In vivo study showed clear accumulation of 123I-chloroquine in the posterior eye of pigmented rats whereas it was absent from albino rat. Interestingly, 123I-nadolol accumulated in to the nasal cavity of pigmented rats. Aromatic iodination changes electronegative properties of compounds and raises their logP (octanol/water partition coefficient) value affecting to the melanin binding positively. Therefore the effect of the radiotracer to the physicochemical properties of the compound and melanin binding should be determined in vitro. This study showed that SPECT/CT imaging method can be used to study melanin binding in vivo. Because the method is semi-quantitative, also a quantitative method should be incorporated to the study in order to have more powerful data. Additional studies are required for statistical analysis.
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(2013)Cellulose has already been used as an industrial raw material for over a century. However, during recent years the nanostructural features of the naturally occurring biopolymer have been fully investigated and characterized through different processing methods as nanofibrillar cellulose (NFC). This has led to a rapid development of novel cellulose based nanoscale materials and advancements in the field of composite materials. NFC offers interesting specific properties that differ from many other natural and synthetic polymers, such as self-renewable raw materials, semi-crystalline morphology, broad chemical modification capacity, biocompatibility and biodegradability. Biocompatibility and the biomimetic aspects of NFC have enabled the fabrication of nanoporous membranes and scaffolds that can function as medical devices (e.g. tissue engineering, wound healing, novel active implants). In this study, the properties of plant-derived NFC, as potential injectable drug releasing hydrogel "implants" were investigated. Three different sized candidate molecules were selected (123I-NaI, 123I-β-CIT and 99mTc-HSA, from small to large respectively) and investigated with the use of a small animal SPECT/CT molecular imaging device. Study compounds were mixed with the NFC biomaterial and injected into the pelvic region of mice. Drug release was observed for a period of 24 hours and the results were compared to saline/study compound control injections. In addition, 99mTc labeled NFC hydrogels were prepared for dual label tracing to observe the hydrogel positioning during the SPECT/CT acquisitions. For the smaller compounds (123I-NaI, 123I-β-CIT), no differences were found in the drug release or absorption in between the NFC biomaterial and saline injections. However, a clear difference was found with the large compound (99mTc-HSA). In the NFC hydrogel, the rate of release was slower and the distribution of 99mTc-HSA was more concentrated around the area of injection. In addition, the NFC hydrogel did not migrate from, or disintegrate, at the site of injection, suggesting a robust enough structural integrity to withstand normal movement and activity. In conclusion, the labeling of NFC was found to be a reliable and simple method. NFC hydrogels have the potential use as drug releasing medical devices with larger compounds. NFC matrix did not have any controlled release effect on the studied small molecules. Therefore further studies are required for more specific conclusions.
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