Should glomerular filtration rate (GFR) be affected by the amount of viable, functioning tubular cells which in turn reflected by absolute renal uptake of Tc-99m DMSA.

Wong Wai Lun.Thesis (M.Phil.)--Chinese University of Hong Kong, 1998.Includes bibliographical references (leaves 119-125).Abstract also in Chinese.Acknowledgments --- p.iLegend for Figures --- p.iiLegend for Tables --- p.ivAbstract --- p.vAbstract in Chinese --- p.ixChapter Chapter I --- Introduction --- p.1Objective --- p.5Chapter Chapter II --- Literature ReviewChapter II.1. --- Anatomy of the urinary system --- p.6Chapter II.2. --- Physiology of the urinary system --- p.10Chapter II.3. --- Methods for investigating the urinary system --- p.12Chapter II.3.1. --- Plain film radiography --- p.12Chapter II.3.2. --- Excretory Urogram --- p.12Chapter II.3.3. --- Ultrasound --- p.13Chapter II.3.4. --- Computed Tomography --- p.15Chapter II.3.5. --- Renal Angiography --- p.16Chapter II.3.6. --- Magnetic Resonance Imaging (MRI) --- p.16Chapter II.3.7. --- Radionuclide Imaging --- p.17Chapter II.4. --- Radiopharmaceuticals for renal parenchyma imaging --- p.17Chapter II.4.1. --- Tc-99m GHA --- p.18Chapter II.4.1.1. --- Chemistry of Tc-99m GHA --- p.18Chapter II.4.1.2. --- Preparation --- p.18Chapter II.4.1.3. --- Doses --- p.18Chapter II.4.1.4. --- Biological behavior --- p.19Chapter II.4.2. --- Tc-99m DMSAChapter II.4.2.1. --- Chemistry of Technetium-99m Dimercaptosuccinic Acid (Tc-99m DMSA) --- p.20Chapter II.4.2.2. --- Chemical property of Tc-99m DMSA --- p.21Chapter II.4.2.3. --- Preparation --- p.22Chapter II.4.2.4. --- Radiochemical purity measurement --- p.22Chapter II.4.2.5. --- Doses --- p.23Chapter II.4.2.6. --- Pharmacokinetic of Tc-99m DMSA --- p.23Chapter II.4.2.7. --- Renal handling of injected Tc-99m DMSA --- p.25Chapter II.5. --- General consideration for quantitative uptake measurement in organs --- p.26Chapter II.5.1. --- Clinical significance of renal Tc-99m DMSA uptake --- p.28Chapter II.5.2. --- Special consideration and problems for quantitative renal Tc-99m uptake measurement --- p.29Chapter II.5.3. --- Suggestions and solutions for quantitative renal Tc-99m uptake measurement --- p.29Chapter II.5.3.1. --- Planar images Vs SPECT images for quantification --- p.29Chapter II.5.3.2. --- Background subtraction --- p.31Chapter II.5.3.3. --- Choice of location for background ROI --- p.32Chapter II.5.3.4. --- Attenuation --- p.35Chapter II.5.3.5. --- Principle of the conjugate view method --- p.36Chapter II.5.3.6. --- Body thickness and kidney depth measurement --- p.37Chapter II.6. --- Glomerular FiltrationChapter II.6.1. --- Introduction --- p.39Chapter II.6.2. --- Gold standard for GFR measurement --- p.40Chapter II.6.3. --- Laboratory studies for the measurement of glomerular filtration : Serum Creatinine and Blood Urea Nitrogen (BUN) levels --- p.41Chapter II.6.3.1. --- Calculation of Creatinine Clearance Rate --- p.43Chapter II.6.3.2. --- Critique for using creatinine clearance as a measurement of renal function --- p.44Chapter II.6.3.3. --- Limitation of the serum creatinine concentration used alone as a measurement of renal function --- p.46Chapter II.6.4. --- Radionuclide technique for the assessment of the glomerular function --- p.48Chapter II.6.4.1. --- Diethylene Triamine Penta Acetic acid (DTPA) --- p.49Chapter II.6.4.2. --- MethodsChapter II.6.4.2.1. --- Measurement of Glomerular Filtration Rate using Tc-99m DTPA with single injection techniques --- p.51Chapter II.6.4.2.2. --- Compartment model --- p.52Chapter II.6.4.2.2a. --- Two-compartment model --- p.52Chapter II.6.4.2.2b. --- Single-compartment model --- p.54Chapter II.6.4.2.3. --- Single blood sample technique: a modification of Tauxe's OIH method in which counts in a single plasma sample correlated with a GFR nomogram --- p.56Chapter II.6.4.2.4. --- Gamma camera based method --- p.58Chapter II.6.4.2.4a. --- Gates-modification of Schlegel's OIH technique --- p.58Chapter II.6.4.2.4b. --- Critique for the Gamma camera technique for measuring GFR --- p.62Chapter II.7. --- The relationship between the Tc-99m DMSA uptake and GFR --- p.67Chapter Chapter III --- Material and Methods --- p.69Chapter III.1. --- Subjects and Sampling Methods --- p.69Chapter III.2. --- Quantitation of Absolute DMSA uptake --- p.70Chapter III.2.1. --- Parameters for Tc-99m DMSA uptake study --- p.70Chapter III.2.1.1. --- Materials and methods --- p.70Chapter III.2.1.1.1. --- Instrumentation --- p.70Chapter III.2.1.1.2. --- Dosage --- p.70Chapter III.2.1.1.3. --- Optimum acquisition start time --- p.70Chapter III.2.1.1.4. --- Length of acquisition time --- p.71Chapter III.2.1.1.5. --- Acquisition parameter --- p.71Chapter III.3. --- Calculation of absolute renal DMSA uptake --- p.72Chapter III.3.1. --- Attenuation Coefficient factor(μ) --- p.73Chapter III.3.2. --- Table attenuation --- p.75Chapter III.3.3. --- Body thickness measurement --- p.77Chapter III.3.4. --- Decay correction --- p.78Chapter III.3.5. --- Calculation of DMSA uptake --- p.78Chapter III.3.6. --- Counting dose injected --- p.80Chapter III.3.7. --- Calculation of absolute quantitation of Tc-99m DMSA uptake --- p.80Chapter III.3.8. --- Dose infiltration --- p.81Chapter III.4. --- GFR measurement --- p.82Chapter III.4.1. --- Instrumentation --- p.82Chapter III.4.2. --- Methods --- p.82Chapter III.5. --- Statistical and analytical methods --- p.84Chapter Chapter IV --- Results --- p.87Chapter IV. 1. --- Characteristics of experimental subjects and their serum creatinine profile --- p.88Chapter IV.2. --- Absolute Tc-99m DMSA uptakeChapter IV.2.1. --- The change of absolute Tc-99m uptake with time --- p.89Chapter IV.2.2. --- Absolute Tc-99m DMSA uptake measurement at 6 and 24 hours --- p.90Chapter IV.2.3. --- Gender difference in absolute Tc-99m uptake measurement at 6 hour --- p.92Chapter IV.3. --- GFR measurement --- p.93Chapter IV.3.1. --- GFR measurement by single (3hr) and double (1&3 hrs) plasma sampling --- p.93Chapter IV.3.2. --- Gender difference in GFR measurement using single plasma sampling --- p.96Chapter IV.4. --- Univariate Correlation --- p.97Chapter IV.4.1. --- Correlation between GFR using single plasma sampling and absolute Tc-99m uptake --- p.97Chapter IV.4.2. --- Correlation between GFR using single plasma sampling and plasma creatinine levels --- p.98Chapter IV.4.3. --- Correlation between anthropometric variables on GFR(3 hr) --- p.99Chapter IV.4.4. --- Correlation between anthropometric variables and serum creatinine plasma level on absolute Tc-99m DMSA uptake measurement at 6 hour --- p.101Chapter IV.4.5. --- Multiple linear stepwise regression --- p.103Chapter Chapter V. --- DiscussionChapter V. 1 --- . Review of the study --- p.104Chapter V.1.1. --- Experimental subjects and their absolute Tc-99m DMSA uptake (%) at 6 hr --- p.104Chapter V.1.2. --- Experimental subjects and their GFR(3 hr) --- p.105Chapter V.2. --- Discussion on subject --- p.105Chapter V.2.1. --- Subject preparation --- p.106Chapter V.3. --- Discussion of method --- p.106Chapter V.3.1. --- Equipment --- p.106Chapter (a) --- Dose calibrator --- p.106Chapter (b) --- The sensitivity of the head 1 and 2 of the gamma camera --- p.106Chapter (c) --- Validation of quantification of injected activity by gamma camera method--------constancy of performance for gamma camera --- p.110Chapter (d) --- LEHR Collimator --- p.112Chapter (f) --- Dead time loss --- p.112Chapter V.4. --- Discussion on measurement --- p.113Chapter (a) --- Length of acquisition time --- p.113Chapter (b) --- Attenuation Coefficient factor (\x) --- p.113Chapter (c) --- "Body thickness, L, measurement" --- p.113Chapter (d) --- Optimum acquisition time for data collection --- p.115Chapter v.5. --- Discussion on overall error estimation --- p.115Chapter (a) --- Tc-99m DMSA uptake measurement at 6 hr --- p.115Chapter (b) --- GFR measurement by single (3 hr) sample --- p.116Chapter Chapter VI --- Conclusion --- p.117Reference --- p.119Appendix I --- p.126Appendix II --- p.128Appendix III --- p.13

Preclinical MRI of the Kidney

This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

Targeted radionuclide therapy: current status and potentials for future improvements

target cell while the absorption of the radioactivity in non-target tissue should be as low as achievable. Usually, this goal is reached by coupling the radionuclide to a vector which recognises a structure, e.g. receptor, on the target cell. By far the most established combination is the somatostatin receptor (sst) and radiolabeled somatostatin analogues. The majority of neuroendocrine tumours feature a strong over-expression of the somatostatin receptors (sst), mainly subtype 2 (sst2). Somatostatin receptors are attractive targets for radiolabelled peptides since the density of sst on tumours is vastly higher than on non tumour tissue. In addition to the favourable receptor distribution, sst2 internalises into the cell after a ligand bound to the receptor. Consequently, radioactivity delivered by the vector is captured in the target cell after binding