Radioactivity isotope tracing
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- MeSH
- dieta MeSH
- injekce subkutánní MeSH
- izotopy rtuti MeSH
- izotopy zinku MeSH
- kadmium krev metabolismus MeSH
- krysa rodu rattus MeSH
- radionuklidy MeSH
- rtuť krev metabolismus MeSH
- selen farmakologie MeSH
- zinek krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imaging agents were used for pretargeting applications utilizing click reactions with a trans-cyclooctene (TCO) tagged targeting vector for a proof of principle both in vitro and in vivo. Starting from FSC, the fluorophores Sulfocyanine-5, Sulfocyanine-7, or IRDye800CW were conjugated, followed by introduction of one or two Tz motifs, resulting in mono and dimeric Tz conjugates. Evaluation included fluorescence microscopy, binding studies, logD, protein binding, in vivo biodistribution, µPET (micro-positron emission tomography), and optical imaging (OI) studies. 68Ga-labeled conjugates showed suitable hydrophilicity, high stability, and specific targeting properties towards Rituximab-TCO pre-treated CD20 expressing Raji cells. Biodistribution studies showed fast clearance and low accumulation in non-targeted organs for both SulfoCy5- and IRDye800CW-conjugates. In an alendronate-TCO based bone targeting model the dimeric IRDye800CW-conjugate resulted in specific targeting using PET and OI, superior to the monomer. This proof of concept study showed that the preparation of FSC-Tz hybrid imaging agents for pretargeting applications is feasible, making such compounds suitable for hybrid imaging applications.
- MeSH
- click chemie MeSH
- fluorescenční protilátková technika MeSH
- kyseliny hydroxamové * chemie MeSH
- multimodální zobrazování * metody MeSH
- optické zobrazování metody MeSH
- ověření koncepční studie MeSH
- pozitronová emisní tomografie MeSH
- radiofarmaka * chemie MeSH
- radioizotopy galia MeSH
- radionuklidy MeSH
- tkáňová distribuce MeSH
- železité sloučeniny * chemie MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The commercial viability of cyclotron-produced (99m)Tc as an alternative to generator-produced (99m)Tc depends on several factors. These include: production yield, ease of target processing and recycling of (100)Mo, radiochemical purity, specific activity as well as the presence of other radionuclides, particularly various Tc radioisotopes that cannot be separated chemically and will remain in the final clinical preparation. These Tc radionuclidic impurities are derived from nuclear interactions of the accelerated protons with other stable Mo isotopes present in the enriched (100)Mo target. The aim of our study was to determine experimentally the yields of Tc radioisotopes produced from these stable Mo isotopes as a function of incident beam energy in order to predict radionuclidic purity of (99m)Tc produced in highly enriched (100)Mo targets of known isotopic composition. METHODS: Enriched molybdenum targets of (95)Mo, (96)Mo, (97)Mo, (98)Mo and (100)Mo were prepared by pressing powdered metal into an aluminum target support. The thick targets were bombarded with 10 to 24MeV protons using the external beam line of the U-120M cyclotron of the Nuclear Physics Institute, Řež. The thick target yields of (94)Tc, (94m)Tc, (95)Tc, (95m)Tc, (96m+g)Tc and (97m)Tc were derived from their activities measured by γ spectrometry using a high purity Ge detector. These data were then used to assess the effect of isotopic composition of highly enriched (100)Mo targets on the radionuclidic purity of (99m)Tc as a function of proton beam energy. Estimates were validated by comparison to measured activities of Tc radioisotopes in proton irradiated, highly enriched (100)Mo targets of known isotopic composition. RESULTS: The measured thick target yields of (94)Tc, (94m)Tc, (95)Tc, (95m)Tc, (96m+g)Tc and (97m)Tc correspond well with recently published values calculated via the EMPIRE-3 code. However, the measured yields are more favourable with regard to achievable radionuclidic purity of (99m)Tc. Reliability of the measured thick target yields was demonstrated by comparison of the estimated and measured activities of (94)Tc, (95)Tc, (95m)Tc, and (96m+g)Tc in highly enriched (100)Mo (99%) targets that showed good agreement, with maximum differences within estimated uncertainties. Radioisotopes (94m)Tc and (97m)Tc were not detected in the irradiated (100)Mo targets due to their low activities and measurement conditions; on the other hand we detected small amounts of the short-lived positron emitter (93)Tc (T(½)=2.75h). In addition to (99m)Tc and trace amounts of the various Tc isotopes, significant activities of (96)Nb, (97)Nb and (99)Mo were detected in the irradiated (100)Mo targets. CONCLUSIONS: Radioisotope formation during the proton irradiation of Mo targets prepared from different, enriched stable Mo isotopes provides a useful data base to predict the presence of Tc radionuclidic impurities in (99m)Tc derived from proton irradiated (100)Mo targets of known isotopic composition. The longer-lived Tc isotopes including (94)Tc (T(½)=4.883h), (95)Tc (T(½)=20.0h), (95m)Tc (T(½)=61 d), (96m+g)Tc (T(½)=4.24 d) and (97m)Tc (T(½)=90 d) are of particular concern since they may affect the dosimetry in clinical applications. Our data demonstrate that cyclotron production of (99m)Tc, using highly enriched (100)Mo targets and 19-24MeV incident proton energy, will result in a product of acceptable radionuclidic purity for applications in nuclear medicine.
Deuterium- and tritium-labeled compounds play a principal role in tracing of biologically active molecules in complicated biochemical systems. The state-of-the-art techniques using noble metal catalysts or strong reducing agents often suffers from low functional group tolerances, poor selectivity, tricky or multistep synthesis of reagents, and low specific activity of the labeled product. Herein, we demonstrate a mild and nonmetallic technique of deuteration and tritiation of polarized double bonds, such as carbonyl compounds, yielding labeled alcohols of high specific activities. This one-pot synthesis uses carrier-free hydrogen gas in situ activated by a freshly prepared frustrated Lewis pair, generating reducing reagents. This labeling strategy shows better selectivity and functional group tolerances compared with current reductive methods. Reported is an example of the selective reduction of the aldehyde moiety of 3-acetylbenzaldehyde. What makes this technology groundbreaking is its mildness, selectivity, and generation of limited amount of radioactive waste as almost no byproducts were generated after use of (B(C6 F5 )33 H)(3 HTMP) reducing reagent. Radiochemical purity of desired 3 H-labeled product in a crude reaction mixture was determined of over 94%. This work provides, to the community of radiochemists, a practical protocol for frustrated Lewis pairs (FLP)-assisted deuterium/tritium labeling technology.
... 177 -- Short Amino Acid Sequences Can Be Analyzed by -- Automated Machines 177 -- Summary 178 -- Tracing ... ... Cellular Molecules with -- Radioactive Isotopes and Antibodies 179 -- Radioactive Atoms Can Be Detected ... ... with Great -- Sensitivity 179 -- Radioisotopes Are Used to Trace Molecules in Cells and Organisms 179 ...
xxxix, 1146 s. : il., tab. ; 28 cm
- MeSH
- biologie buňky MeSH
- molekulární biologie MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
- cytologie, klinická cytologie
