We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [18F]fluorocholine.
- MeSH
- apoptóza MeSH
- cholin analogy a deriváty farmakokinetika MeSH
- lidé MeSH
- myši SCID MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádory prostaty diagnostické zobrazování metabolismus patologie MeSH
- pozitronová emisní tomografie MeSH
- proliferace buněk MeSH
- radioaktivní indikátory * MeSH
- radiofarmaka farmakokinetika MeSH
- radioizotopy fluoru farmakokinetika MeSH
- radioizotopy jodu farmakokinetika MeSH
- tkáňová distribuce MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cholin MeSH
- fluorocholine MeSH Prohlížeč
- Iodine-125 MeSH Prohlížeč
- radioaktivní indikátory * MeSH
- radiofarmaka MeSH
- radioizotopy fluoru MeSH
- radioizotopy jodu MeSH
PURPOSE: The purpose of this study was to evaluate a set of widely used nuclear medicine imaging agents as possible methods to study the early effects of systemic inflammation on the living brain in a mouse model of sepsis-associated encephalopathy (SAE). The lipopolysaccharide (LPS)-induced murine systemic inflammation model was selected as a model of SAE. PROCEDURES: C57BL/6 mice were used. A multimodal imaging protocol was carried out on each animal 4 h following the intravenous administration of LPS using the following tracers: [99mTc][2,2-dimethyl-3-[(3E)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(3E)-3-hydroxyiminobutan-2-yl]azanide ([99mTc]HMPAO) and ethyl-7-[125I]iodo-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate ([125I]iomazenil) to measure brain perfusion and neuronal damage, respectively; 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) to measure cerebral glucose uptake. We assessed microglia activity on another group of mice using 2-[6-chloro-2-(4-[125I]iodophenyl)-imidazo[1,2-a]pyridin-3-yl]-N-ethyl-N-methyl-acetamide ([125I]CLINME). Radiotracer uptakes were measured in different brain regions and correlated. Microglia activity was also assessed using immunohistochemistry. Brain glutathione levels were measured to investigate oxidative stress. RESULTS: Significantly reduced perfusion values and significantly enhanced [18F]FDG and [125I]CLINME uptake was measured in the LPS-treated group. Following perfusion compensation, enhanced [125I]iomazenil uptake was measured in the LPS-treated group's hippocampus and cerebellum. In this group, both [18F]FDG and [125I]iomazenil uptake showed highly negative correlation to perfusion measured with ([99mTc]HMPAO uptake in all brain regions. No significant differences were detected in brain glutathione levels between the groups. The CD45 and P2Y12 double-labeling immunohistochemistry showed widespread microglia activation in the LPS-treated group. CONCLUSIONS: Our results suggest that [125I]CLINME and [99mTc]HMPAO SPECT can be used to detect microglia activation and brain hypoperfusion, respectively, in the early phase (4 h post injection) of systemic inflammation. We suspect that the enhancement of [18F]FDG and [125I]iomazenil uptake in the LPS-treated group does not necessarily reflect neural hypermetabolism and the lack of neuronal damage. They are most likely caused by processes emerging during neuroinflammation, e.g., microglia activation and/or immune cell infiltration.
- Klíčová slova
- LPS, Microglia activation, Neuroinflammation, PET/MRI, SPECT/CT, Systemic infection, [125I]CLINME, [125I]iomazenil, [18F]FDG, [99mTc]HMPAO,
- MeSH
- fluorodeoxyglukosa F18 farmakokinetika MeSH
- glukosa metabolismus MeSH
- jednofotonová emisní výpočetní tomografie metody MeSH
- lipopolysacharidy MeSH
- modely nemocí na zvířatech MeSH
- mozek diagnostické zobrazování metabolismus MeSH
- multimodální zobrazování metody MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neurozobrazování metody MeSH
- nukleární lékařství metody MeSH
- pozitronová emisní tomografie metody MeSH
- radioaktivní indikátory * MeSH
- radioisotopová scintigrafie metody MeSH
- radioizotopy jodu farmakokinetika MeSH
- septická encefalopatie chemicky indukované diagnóza metabolismus patologie MeSH
- technecium 99mTc exametazim farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fluorodeoxyglukosa F18 MeSH
- glukosa MeSH
- Iodine-125 MeSH Prohlížeč
- lipopolysacharidy MeSH
- radioaktivní indikátory * MeSH
- radioizotopy jodu MeSH
- technecium 99mTc exametazim MeSH
In recent years, several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of theranostic radiopharmaceuticals for the treatment of prostate cancer (PC). In the second decade of the 21st century, a new era in nuclear medicine was initiated by the clinical introduction of small-molecule PSMA inhibitor radioligands, 40 y after the clinical introduction of 18F-FDG. Because of the high incidence and mortality of PC, the new PSMA radioligands have already had a remarkable impact on the clinical management of PC. For the continuing clinical development and long-term success of theranostic agents, designing modern prospective clinical trials in theranostic nuclear medicine is essential. First-in-human studies with PSMA radioligands derived from small-molecule PSMA inhibitors showed highly sensitive imaging of PSMA-positive PC by means of PET and SPECT as well as a dramatic response of metastatic castration-resistant PC after PSMA radioligand therapy. This tremendous success logically led to the initiation of prospective clinical trials with several PSMA radioligands. Meanwhile, MIP-1404, PSMA-11, 2-(3-{1-carboxy-5-[(6-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (DCFPyL), PSMA-617, PSMA-1007, and others have entered or will enter prospective clinical trials soon in several countries. The significance becomes apparent by, for example, the considerable increase in the number of publications about PSMA-targeted PET imaging from 2013 to 2016 (e.g., a search of the Web of Science for "PSMA" AND "PET" found only 19 publications in 2013 but 218 in 2016). Closer examination of the initial success of PC treatment with PSMA inhibitor radiotracers leads to several questions from the basic research perspective as well as from the perspective of clinical demands: What lessons have been learned regarding the design of PSMA radioligands that have already been developed? Has an acceptable compromise between optimal PSMA radioligand design and a broad range of clinical demands been reached? Can the lessons learned from multiple successes within the PSMA experience be transferred to further theranostic approaches?
- Klíčová slova
- PSMA radiotracers, prostate cancer, radioligand therapy, small-molecule PSMA inhibitors, theranostic PSMA radioligands,
- MeSH
- antigeny povrchové MeSH
- diagnóza * MeSH
- glutamátkarboxypeptidasa II antagonisté a inhibitory MeSH
- lidé MeSH
- močovina chemie farmakologie terapeutické užití MeSH
- molekulová hmotnost MeSH
- objevování léků metody MeSH
- radioaktivní indikátory MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antigeny povrchové MeSH
- FOLH1 protein, human MeSH Prohlížeč
- glutamátkarboxypeptidasa II MeSH
- močovina MeSH
- radioaktivní indikátory MeSH
BACKGROUND: Certain studies suggest that using indocyanine green (ICG) could be comparable with using radioisotopes (RI) in detecting sentinel lymph nodes (SLNs) in breast cancer. A number of these studies were performed in Asia. The objective of our pilot study was to evaluate within a European population of breast cancer patients the detection rate of SLNs using ICG and the HyperEye system and the concordance in SLNs detected using this method and the standard method involving RI and a gamma probe. METHODS: Ten female patients with early-stage breast cancer (Czech Republic) indicated for partial mastectomy and SLN biopsy were subjected to standard application of RI. Before surgery, ICG was administered periareolarly in the amount of 1 ml of 0.5% solution. Sentinel lymph nodes were first detected perioperatively exclusively using ICG fluorescence and the HyperEye device (Mizuho, Japan). Only after removal of all SLNs found in this way was the standard hand-held gamma probe used to detect RI, and any potential additional SLNs not found with ICG were then extirpated. RESULTS: In all 10 cases, at least one SLN was successfully detected using ICG. Nevertheless, in five patients, 1-4 additional SLNs were found using the gamma probe. Complete concordance in detecting SLNs therefore occurred in only one half of the cases. Metastases in SLNs were found in a total of two cases. Had we used only ICG for detection, one of these two cases would have been incorrectly evaluated as N0 (ICG false negativity). CONCLUSIONS: The study did not confirm the hypothesis that the use of ICG with the HyperEye system can currently be considered a method fully comparable with using RI and a gamma probe in a population of European patients. Although the detection rate is high, a significantly lower number of SLNs were detected using ICG than using RI (p = 0.03). Thus, there would be a higher probability for false negatives to occur in using SLN biopsy. This is caused mainly by the limited permeability of tissues to fluorescent radiation and the difficulty therefore of detecting nodes located deeper beneath the body's surface.
- Klíčová slova
- Breast cancer, Fluorescence, HyperEye, Indocyanine green, Sentinel lymph node biopsy,
- MeSH
- biopsie sentinelové lymfatické uzliny metody MeSH
- fluorescence MeSH
- fluorescenční barviva aplikace a dávkování MeSH
- indokyanová zeleň aplikace a dávkování MeSH
- injekce intradermální MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mastektomie MeSH
- nádory prsu diagnostické zobrazování patologie chirurgie MeSH
- pilotní projekty MeSH
- radioaktivní indikátory MeSH
- sentinelová uzlina diagnostické zobrazování MeSH
- staging nádorů MeSH
- technecium 99mTc-agregovaný albumin aplikace a dávkování MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- fluorescenční barviva MeSH
- indokyanová zeleň MeSH
- radioaktivní indikátory MeSH
- technecium 99mTc-agregovaný albumin MeSH
- technetium Tc 99m nanocolloid MeSH Prohlížeč
Ligands with geminal bis(phosphonic acid) appended to 1,4,7-triazacyclonone-1,4-diacetic acid fragment through acetamide (NOTAM(BP) ) or methylenephosphinate (NO2AP(BP) ) spacers designed for (68) Ga were prepared. Ga(III) complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no-carrier-added (68) Ga. For both ligands, formation of Ga(III) complex was slower than that with NOTA owing to the strong out-of-cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C and in a narrow acidity region (pH ~3). At higher temperature, hydrolysis of amide bond of the carboxamide-bis(phosphonate) conjugate was observed during complexation reaction leading to Ga-NOTA complex. In vitro sorption studies confirmed effective binding of the (68) Ga complexes to hydroxyapatite being comparable with that found for common bis(phosphonate) drugs such as pamindronate. Selective bone uptake was confirmed in healthy rats by biodistribution studies ex vivo and by positron emission tomography imaging in vivo. Bone uptake was very high, with SUV (standardized uptake value) of 6.19 ± 1.27 for [(68) Ga]NO2AP(BP) ) at 60 min p.i., which is superior to uptake of (68) Ga-DOTA-based bis(phosphonates) and [(18) F]NaF reported earlier (SUV of 4.63 ± 0.38 and SUV of 4.87 ± 0.32 for [(68) Ga]DO3AP(BP) and [(18) F]NaF, respectively, at 60 min p.i.). Coincidently, accumulation in soft tissue is generally low (e.g. for kidneys SUV of 0.26 ± 0.09 for [(68) Ga]NO2AP(BP) at 60 min p.i.), revealing the new (68) Ga complexes as ideal tracers for noninvasive, fast and quantitative imaging of calcified tissue and for metastatic lesions using PET or PET/CT.
- Klíčová slova
- 68Ga radiopharmaceuticals, NOTA derivatives, PET imaging, bis(phosphonate), bone targeting, in vivo imaging, macrocyclic complexes, nuclear medicine, phosphinate complexes, radiotracer biodistribution,
- MeSH
- bisfosfonáty * chemie farmakokinetika farmakologie MeSH
- femur diagnostické zobrazování metabolismus MeSH
- galium * chemie farmakokinetika farmakologie MeSH
- kontrastní látky * chemie farmakokinetika farmakologie MeSH
- krysa rodu Rattus MeSH
- pozitronová emisní tomografie metody MeSH
- radioaktivní indikátory * MeSH
- radiografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bisfosfonáty * MeSH
- galium * MeSH
- kontrastní látky * MeSH
- radioaktivní indikátory * MeSH
Recently, the role of energy savings in indoor air quality deterioration has been extensively emphasised, predominantly in the context of significant air exchange rate reduction as a result of home energy retrofits. In case of refurbishment of existing buildings, the effect of energy-efficient technologies on indoor radon concentration is considerably complex and has to be carefully evaluated with respect to radon entry rate (RER) and air exchange rate alteration. For the purpose of detailed analysis of radon entry pathways, the unique infiltration experiment has been carried out using the tracer gas (N2O) method application in field conditions. Significant amount of experimental works has been done to provide an independent assessment of RER and air-exchange rate facilitating the analysis of fundamental factors influencing the indoor radon variations (e.g. indoor-outdoor pressure difference induced by wind, stack effect, heating, ventilation and operation of air-conditioning systems).
- MeSH
- bydlení * MeSH
- lidé MeSH
- monitorování radiace metody MeSH
- oxid dusičitý analýza MeSH
- plyny analýza MeSH
- radioaktivní indikátory * MeSH
- radioaktivní látky znečišťující vzduch analýza MeSH
- radon analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- oxid dusičitý MeSH
- plyny MeSH
- radioaktivní indikátory * MeSH
- radioaktivní látky znečišťující vzduch MeSH
- radon MeSH
When a patient is examined by positron emission tomography (PET), radiotracer dose amount (activity) has to be determined. However, the rules for activity correction according to patients' weight used nowadays do not correspond with practical experience. Very high image quality is achieved for slim patients, whereas noisy images are produced for obese patients. There is opportunity to modify the correction rule with the aim to equalize image quality within the broad spectrum of patients and to diminish radiation risk to slim patients, with special importance for children. We have built a model of a particular PET scanner and approximated human trunk, which is our region of interest, by a cylindrical model with segments of liver, outer adipose tissue, and the rest. We have performed Monte Carlo simulations of PET imaging using the GATE simulation package. Under reasonably simplifying assumptions and for special parameters, we have developed curves that recommend amount of injected activity based on body parameters to give PET images of constant quality, the quality being expressed in terms of noise equivalent counts. The dependence qualitatively differs from the rules used in clinical practice nowadays, and the results indicate potential for improvement.
- Klíčová slova
- Monte Carlo simulation, biological system modeling, image quality, positron emission tomography,
- MeSH
- biologické modely MeSH
- dávka záření * MeSH
- fantomy radiodiagnostické MeSH
- index tělesné hmotnosti MeSH
- lidé MeSH
- metoda Monte Carlo * MeSH
- počítačová rentgenová tomografie MeSH
- počítačová simulace MeSH
- počítačové zpracování obrazu MeSH
- pozitronová emisní tomografie metody MeSH
- radioaktivní indikátory MeSH
- trup diagnostické zobrazování fyziologie MeSH
- velikost těla fyziologie MeSH
- výpočet dávky léku * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- radioaktivní indikátory MeSH
PURPOSE: This study assessed the effect of different levels of tracer uptake in the infarcted area on improvement of left ventricular function in patients treated by intracoronary mononuclear bone marrow cell (BMC) transplantation during long-term (12-month) follow-up. METHODS: Thirty-seven patients with irreversible injury after their first acute myocardial infarction, as confirmed by dobutamine echocardiography and sestamibi single-photon emission computed tomography/fluorodeoxyglucose positron emission tomography underwent BMC transplantation (1 × 10(8) cells), whereas 36 similar patients were randomly assigned to a control group. RESULTS: In 16 BMC-treated patients with very low sestamibi uptake (<30% of maximum) in the infarcted area, the mean baseline left ventricular ejection fraction (LVEF) increased at 3- and 12-month follow-up by 3% and 4% only, and mean end-diastolic/end-systolic volumes (EDV/ESV) enlarged by 20/7 mL and 23/9 mL, respectively (P = NS vs. controls). In 21 BMC-treated patients with higher sestamibi uptake (31%-50% of maximum), the LVEF improved by 6% and 7%, and EDV/ESV decreased by 4/13 mL and 1/13 mL, respectively (P < 0.05 vs. BMC-treated subgroup with low uptake and control subjects). There was no statistically significant difference in LVEF, EDV, or ESV changes between controls with low versus higher sestamibi uptake. CONCLUSION: During long-term follow-up, the post-transplant improvement of left ventricular function remained significant only in BMC-treated patients with higher sestamibi uptake.
- MeSH
- biologický transport MeSH
- časové faktory MeSH
- dysfunkce levé srdeční komory diagnostické zobrazování metabolismus MeSH
- fluorodeoxyglukosa F18 * metabolismus MeSH
- infarkt myokardu diagnostické zobrazování patologie patofyziologie chirurgie MeSH
- koronární cévy patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- pozitronová emisní tomografie * MeSH
- radioaktivní indikátory MeSH
- senioři MeSH
- srdeční akcí synchronizovaná jednofotonová emisní počítačová tomografie * MeSH
- technecium 99mTc sestamibi * metabolismus MeSH
- transplantace kostní dřeně * MeSH
- výběr pacientů * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- fluorodeoxyglukosa F18 * MeSH
- radioaktivní indikátory MeSH
- technecium 99mTc sestamibi * MeSH
A comparative study of the factors of non-specific protection and specific immunity, allergic and autoallergic reactivity during prolonged introduction into the organism of experimental animals of 6 different radioactive and 7 harmful chemical substances was carried out. Qualitative and quantitative peculiarities were found in the changes in immunological reactivity during exposure of the organism to radionuclides and stable chemical compounds. Impairment of immunity plays a substantial role in the course and outcome of affections provoked by chronic effect of the substances examined.
- MeSH
- autoprotilátky MeSH
- časové faktory MeSH
- diaminy metabolismus MeSH
- imunita * MeSH
- komplement fixační testy MeSH
- králíci MeSH
- krysa rodu Rattus MeSH
- lymfoidní tkáň imunologie MeSH
- muramidasa imunologie MeSH
- myši MeSH
- olovo metabolismus MeSH
- radioaktivní indikátory * MeSH
- radionuklidy * MeSH
- rtuť metabolismus MeSH
- stroncium metabolismus MeSH
- voda * MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu Rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- autoprotilátky MeSH
- diaminy MeSH
- muramidasa MeSH
- olovo MeSH
- radioaktivní indikátory * MeSH
- radionuklidy * MeSH
- rtuť MeSH
- stroncium MeSH
- voda * MeSH
