Biodistribution analyses of nanocarriers are often performed with optical imaging. Though dye tags can interact with transporters, e.g., organic anion transporting polypeptides (OATPs), their influence on biodistribution was hardly studied. Therefore, this study compared tumor cell uptake and biodistribution (in A431 tumor-bearing mice) of four near-infrared fluorescent dyes (AF750, IRDye750, Cy7, DY-750) and dye-labeled poly(N-(2-hydroxypropyl)methacrylamide)-based nanocarriers (dye-pHPMAs). Tumor cell uptake of hydrophobic dyes (Cy7, DY-750) was higher than that of hydrophilic dyes (AF750, IRDye750), and was actively mediated but not related to OATPs. Free dyes' elimination depended on their hydrophobicity, and tumor uptake correlated with blood circulation times. Dye-pHPMAs circulated longer and accumulated stronger in tumors than free dyes. Dye labeling significantly influenced nanocarriers' tumor accumulation and biodistribution. Therefore, low-interference dyes and further exploration of dye tags are required to achieve the most unbiased results possible. In our assessment, AF750 and IRDye750 best qualified for labeling hydrophilic nanocarriers.

• Klíčová slova
• Biodistribution, Drug delivery system, Fluorescent dye-labeling, Molecular imaging, Optical imaging,
• MeSH
• fluorescenční barviva chemie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory * diagnostické zobrazování   farmakoterapie   MeSH
• nosiče léků * chemie   MeSH
• optické zobrazování MeSH
• tkáňová distribuce MeSH
• zkreslení výsledků (epidemiologie) MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluorescenční barviva MeSH
• nosiče léků * MeSH

The Turkevich method was optimized to prepare gold nanoparticles (AuNP) stabilized by polyethyleneglycol (PEG) for µCT. Using various independent modalities, we thoroughly characterized the optimized PEG-AuNPs. Here, we show that PEG-AuNPs are retained in the blood and provide a high contrast in the high-resolution µCT imaging of blood vessels and inner organs. The biodistribution is characterized by prolonged circulation in the blood and accumulation in the liver, spleen and skin. The accumulation of AuNP in the skin resulted in the blue discoloration of eyes and the whole skin. In vitro experiments using a leukemic monocyte THP-1 cell line model expressing high levels of NLRP3 demonstrated that the NLRP3inflammasome was not activated by PEG AuNP. Over 9 months, the mice were scanned by µCT and were in good health. Scans in mice using PEG-stabilized AuNPs in this study were sharper, with a higher contrast, when compared to a commercial contrasting agent at the same dose. The PEG-AuNPs were morphologically and chemically stable for at least two years when stored in the refrigerator.

• Klíčová slova
• biodistribution, gold nanoparticles, in vivo imaging, microcomputer tomography, nanotoxicology,
• Publikační typ
• časopisecké články MeSH

Rheumatoid arthritis is a chronic inflammatory autoimmune disease caused by alteration of the immune system. Current therapies have several limitations and the use of nanomedicines represents a promising strategy to overcome them. By employing a mouse model of adjuvant induced arthritis, we aimed to evaluate the biodistribution and therapeutic effects of glucocorticoid dexamethasone conjugated to a nanocarrier based on biocompatible N-(2-hydroxypropyl) methacrylamide copolymers. We observed an increased accumulation of dexamethasone polymer nanomedicines in the arthritic mouse paw using non-invasive fluorescent in vivo imaging and confirmed it by the analysis of tissue homogenates. The dexamethasone conjugate exhibited a dose-dependent healing effect on arthritis and an improved therapeutic outcome compared to free dexamethasone. Particularly, significant reduction of accumulation of RA mediator RANKL was observed. Overall, our data suggest that the conjugation of dexamethasone to a polymer nanocarrier by means of stimuli-sensitive spacer is suitable strategy for improving rheumatoid arthritis therapy.

• Klíčová slova
• Biodistribution, Dexamethasone, HPMA, RANKL, Rheumatoid arthritis,
• MeSH
• artritida experimentální farmakoterapie   patologie   MeSH
• dexamethason * chemie   farmakokinetika   aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• myši MeSH
• nanočástice chemie   MeSH
• nosiče léků chemie   farmakokinetika   MeSH
• polymery * chemie   farmakokinetika   MeSH
• revmatoidní artritida * farmakoterapie   patologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dexamethason * MeSH
• nosiče léků MeSH
• polymery * MeSH

Horseradish peroxidase (HRP)/H2O2-mediated crosslinking of polypeptides in inverse miniemulsion is a promising approach for the development of next-generation biocompatible and biodegradable nanogels. Herein, we present a fundamental investigation of the effects of three surfactants and their different concentrations on the (HRP)/H2O2-mediated nanogelation of poly[N5-(2-hydroxyethyl)-l-glutamine-ran-N5-propargyl-l-glutamine-ran-N5-(6-aminohexyl)-l-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-l-glutamine] (PHEG-Tyr) in inverse miniemulsion. The surfactants sorbitan monooleate (SPAN 80), polyoxyethylenesorbitan trioleate (TWEEN 85), and dioctyl sulfosuccinate sodium salt (AOT) were selected and their influence on the nanogel size, size distribution, and morphology was evaluated. The most effective nanogelation stabilization was achieved with 20 wt% nonionic surfactant SPAN 80. The diameter of the hydrogel nanoparticles was 230 nm (dynamic light scattering, DLS) and was confirmed also by nanoparticle tracking analysis (NTA) which showed the diameters ranging from 200 to 300 nm. Microscopy and image analyses showed that the nanogel in the dry state was spherical in shape and had number-average diameter Dn = 26 nm and dispersity Ð = 1.91. In the frozen-hydrated state, the nanogel appeared porous and was larger in size with Dn = 182 nm and Ð = 1.52. Our results indicated that the nanogelation of the polymer precursor required a higher concentration of surfactant than classical inverse miniemulsion polymerization to ensure effective stabilization. The developed polypeptide nanogel was radiolabeled with 125I, and in vivo biodistribution and blood clearance evaluations were performed. We found that the 125I-labeled nanogel was well-biodistributed in the bloodstream, cleared from mouse blood during 48 h by renal and hepatic pathways and did not provoke any sign of toxic effects.

• Klíčová slova
• Blood clearance, Inverse miniemulsion, Nanogel, Polypeptide, Surfactant, in vivo biodistribution,
• MeSH
• myši MeSH
• nanogely MeSH
• peptidy MeSH
• peroxid vodíku * MeSH
• polyethylenglykoly MeSH
• polyethylenimin MeSH
• povrchově aktivní látky * MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nanogely MeSH
• peptidy MeSH
• peroxid vodíku * MeSH
• polyethylene glycol polyethyleneimine nanogel MeSH Prohlížeč
• polyethylenglykoly MeSH
• polyethylenimin MeSH
• povrchově aktivní látky * MeSH

Drug delivery systems based on thermoresponsive polymers might serve as suitable carriers for local radiotherapy. We have, therefore, designed and synthesized a radioiodine-labellable thermoresponsive polymer. The polymer was synthesized by copolymerization of N-isopropylacrylamide with N-methacryloyl tyrosinamide in tetrahydrofuran, and then labelled by (131)I. The solution of this labelled polymer in dimethylsulfoxide (4.4 MBq/ml; 1.8 wt% polymer) was applied to femoral muscle of male Balb/C mice (50 microl per animal). The biodistribution and excretion of radioactivity was followed in 2h and 1, 7, 14, 28 and 42 d post injection (n=6 per time point). As expected, the labelled polymer was left on the application site (ca 90% 2h post injection), decreasing slowly to ca 80% within 14 d. At 28 d post injection, ca 70% of the injected activity was still found on the application site, decreasing to ca 60% at 42 d. No organ-specific accumulation of the radioactivity released from the application site, including thyroid, was observed. Majority of the released radioactivity was excreted via urine and faeces. This preliminary study suggests that thermoresponsive polymers could be used as an effective delivery system for localized radiotherapy.

• MeSH
• akrylamidy chemie   MeSH
• akrylové pryskyřice aplikace a dávkování   chemická syntéza   farmakokinetika   terapeutické užití   MeSH
• kosterní svaly metabolismus   MeSH
• methakryláty chemie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• radiofarmaka chemická syntéza   farmakokinetika   terapeutické užití   MeSH
• radioizotopy jodu MeSH
• radioterapie metody   MeSH
• systémy cílené aplikace léků metody   MeSH
• teplota MeSH
• tkáňová distribuce MeSH
• tyrosin analogy a deriváty   chemie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• akrylové pryskyřice MeSH
• methakryláty MeSH
• N-isopropylacrylamide MeSH Prohlížeč
• N-methacryloyl tyrosinamide MeSH Prohlížeč
• radiofarmaka MeSH
• radioizotopy jodu MeSH
• tyrosin MeSH

Androgen deprivation therapy (ADT) is known to influence the prostate-specific membrane antigen (PSMA) expression of prostate cancer, potentially complicating the interpretation of PSMA ligand PET findings and affecting PSMA radioligand therapy. However, the impact of ADT on PSMA ligand biodistribution in nontumorous organs is not well understood. Methods: Men (n = 112) with histologically proven prostate cancer who underwent 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) PET/CT between November 2015 and July 2021 at the Medical University Vienna with known ADT status were retrospectively recruited. Fifty-six patients were on gonadotropin-releasing hormone-interfering ADT at the time of imaging (ADT group), whereas 56 patients with no history of ADT served as a control group. Physiologically PSMA-expressing organs (salivary glands, kidneys, liver, and spleen) were delineated, and their uptake was compared according to their data distributions. Multivariate regression analysis assessed the relationship between renal, hepatic, splenic, and salivary gland uptake and the explanatory variables metabolic tumor volume, glomerular filtration rate, and ADT status. Results: ADT was associated with lower levels of PSMA uptake in the kidneys (SUVmean: Δ[ADT - control] = -7.89; 95% CI, -10.73 to -5.04; P < 0.001), liver (SUVpeak: Δ[ADT - control] = -2.3; 95% CI, -5.72 to -0.93; P = 0.003), spleen (SUVpeak: Δ[ADT - control] = -1.27; 95% CI, -3.61 to -0.16; P = 0.033), and salivary glands (SUVmean: Δ[ADT - control] = -1.04; 95% CI, -2.48 to -0.13; P = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUVmean: β = -7.95; 95% CI, -11.06 to -4.84; P < 0.0001), hepatic (SUVpeak: β = -7.85; 95% CI, -11.78 to -3.91; P < 0.0001), splenic (SUVpeak: β = -5.83; 95% CI, -9.95 to -1.7; P = 0.006), and salivary gland (SUVmean: β = -1.47; 95% CI, -2.76 to -0.17; P = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUVmean (β = 0.16; 95% CI, 0.05 to 0.26; P = 0.0034). Conclusion: These findings suggest that ADT systemically modulates PSMA expression, which may have implications for treatment-optimizing and side-effect-minimizing strategies for PSMA radioligand therapies, particularly those using more potent 225Ac-labeled PSMA conjugates.

• Klíčová slova
• PSMA PET, androgen deprivation therapy, biodistribution, prostate cancer,
• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• EDTA MeSH
• lidé MeSH
• ligandy MeSH
• nádory prostaty * patologie   MeSH
• PET/CT metody   MeSH
• radioizotopy galia MeSH
• retrospektivní studie MeSH
• tkáňová distribuce MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté androgenů MeSH
• EDTA MeSH
• gallium 68 PSMA-11 MeSH Prohlížeč
• ligandy MeSH
• N,N'-bis(2-hydroxy-5-(ethylene-beta-carboxy)benzyl)ethylenediamine N,N'-diacetic acid MeSH Prohlížeč
• radioizotopy galia MeSH

BACKGROUND AND METHODS: In this study, we investigated the biodistribution and elimination characteristics of a new radiolabelled somatostatin analogue, 99mTc demotate 1, in rats by in-vivo biodistribution and elimination experiments, perfused rat liver and kidney experiments and micro-autoradiography of renal tissue. RESULTS: Rapid clearance from blood and most organs was found. High and long-term uptake in organs with high density of somatostatin receptors (the adrenals and pancreas) and in stomach and intestine was reduced in non-radiolabelled octreotide pretreated animals. The predominant urine excretion was associated with an accumulation of 99mTc demotate 1 in the kidney, mainly in the renal cortex. This uptake was not affected by non-radiolabelled octreotide pretreatment. CONCLUSION: 99mTc demotate 1 is a prospective radiopharmaceutical for use in human medicine in somatostatin receptor-positive tumour imaging and its potential should be confirmed in further experiments and clinical trials.

• MeSH
• cyklické peptidy farmakokinetika   MeSH
• játra diagnostické zobrazování   metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny diagnostické zobrazování   metabolismus   MeSH
• metabolická clearance MeSH
• organotechneciové sloučeniny farmakokinetika   MeSH
• orgánová specificita MeSH
• potkani Wistar MeSH
• radiofarmaka farmakokinetika   MeSH
• radioisotopová scintigrafie MeSH
• receptory somatostatinu metabolismus   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklické peptidy MeSH
• organotechneciové sloučeniny MeSH
• radiofarmaka MeSH
• receptory somatostatinu MeSH
• technetium Tc 99m demotate MeSH Prohlížeč

AIM: The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model. METHODS: The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used. RESULTS: The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative. CONCLUSIONS: The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

• MeSH
• alloxan MeSH
• experimentální diabetes mellitus krev   MeSH
• fixní kombinace léků MeSH
• glibenklamid analogy a deriváty   farmakokinetika   terapeutické užití   MeSH
• hypoglykemika metabolismus   farmakokinetika   MeSH
• krevní glukóza metabolismus   MeSH
• krysa rodu Rattus MeSH
• metformin terapeutické užití   MeSH
• potkani Wistar MeSH
• pregnenolon farmakokinetika   terapeutické užití   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alloxan MeSH
• fixní kombinace léků MeSH
• glibenklamid MeSH
• hypoglykemika MeSH
• krevní glukóza MeSH
• metformin MeSH
• pregnenolon MeSH

BACKGROUND: In this study, two octreotate derivatives N-[4-carboxy-4-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl]butanoyl]-Tyr(3)-octreotate (DOTAGA-tate) and N-[[4,10-bis(carboxymethyl)-7-(1(1,3-dicarboxypropyl))-1,4,7,10-tetraaza-cyclododec-1-yl]acetyl]-Tyr(3)-octreotate (DOTA-t-GA-tate) were radio-labeled with (111)In or (88)Y and their biodistribution profiles together with their elimination characteristics in rats were compared. MATERIALS AND METHODS: Radiolabeling of the peptides with high radiochemical purity was carried out in an acetate buffer with gentisic acid as radioprotective compound. Biodistribution profiles of the radiolabeled peptides were determined in intact male Wistar rats after an intravenous dose of 1 microg/kg. For elimination pathways analysis, studies in intact rats in metabolic cages and perfused rat kidney and liver were carried out. RESULTS: Fast radioactivity clearance from rat tissues (excepting somatostatin receptor-rich organs and the kidney) was determined for all agents under study. Profound radioactivity uptake in organs with a high density of somatostatin receptors (namely the adrenals and pancreas as biomarkers of somatostatin receptor-positive tissue) was slightly higher for radiolabeled DOTAGA-tate when compared with DOTA-t-GA-tate. Significantly higher accumulation in kidney and somewhat lower urinary elimination of (111)In-labeled peptides in comparison with that of (88)Y-agents were determined. Perfused rat kidney experiments confirmed that glomerular filtration was the main elimination mechanism for the compounds under study; their bile clearances in the perfused rat liver were negligible. CONCLUSION: (111)In((88)Y)-DOTAGA-tates exhibited higher distribution into somatostatin receptor-rich organs when compared with the corresponding radiolabeled DOTA-t-GA-tates. Higher uptake of (111)In-labeled peptides in the kidney is attributed to its different coordination properties.

• MeSH
• krysa rodu Rattus MeSH
• ledviny metabolismus   MeSH
• oktreotid analogy a deriváty   chemie   farmakokinetika   MeSH
• potkani Wistar MeSH
• radiofarmaka chemie   farmakokinetika   MeSH
• radioizotopy india * MeSH
• radioizotopy ytria * MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• oktreotid MeSH
• radiofarmaka MeSH
• radioizotopy india * MeSH
• radioizotopy ytria * MeSH
• Y-DOTA-t-GA-tate MeSH Prohlížeč
• Y-DOTAGA-tate MeSH Prohlížeč

BACKGROUND: (68)Ga-triacetylfusarinine C (TAFC) and (68)Ga-ferrioxamine E (FOXE) show great potential to be used as highly sensitive and selective tracers for Aspergillus infection imaging. Here we report on a comparison of the ex vivo biodistribution and small animal imaging of (68)Ga-TAFC and (68)Ga-FOXE versus (68)Ga-colloid and (68)Ga-citrate as unspecific control in mice. METHODS: The radiochemical purity of tested (68)Ga labelled tracers was determined by RP-HPLC or ITLC-SG. Ex vivo biodistribution was studied in normal DBA/2 mice 30 min and 90 min p.i. Static and dynamic imaging were performed using µPET/CT. RESULTS: (68)Ga-TAFC and (68)Ga-FOXE showed rapid renal excretion and low blood values even 90 min p.i. (68)Ga-TAFC showed almost no retention in other organs while (68)Ga-FOXE displayed some uptake in gastrointestinal tract. (68)Ga-colloid and (68)Ga-citrate revealed significantly different ex vivo biodistribution. (68)Ga-colloid showed pronounced radioactivity retention in the liver, while (68)Ga-citrate displayed high blood values and significant retention of radioactivity in highly perfused organs. CONCLUSIONS: From the results, both (68)Ga-TAFC and (68)Ga-FOXE have excellent and significantly different in vivo behaviour compared to (68)Ga-colloid and (68)Ga-citrate. (68)Ga-TAFC in particular confirmed its great potential use as a specific tracer for Aspergillus infection imaging.

• MeSH
• aspergilóza diagnostické zobrazování   metabolismus   MeSH
• citráty farmakokinetika   MeSH
• cyklické peptidy farmakokinetika   MeSH
• diagnostické zobrazování * MeSH
• galium farmakokinetika   MeSH
• heterocyklické sloučeniny monocyklické farmakokinetika   MeSH
• koloidy MeSH
• myši inbrední DBA MeSH
• myši MeSH
• pozitronová emisní tomografie metody   MeSH
• radiofarmaka farmakokinetika   MeSH
• radioizotopy galia MeSH
• siderofory MeSH
• somatostatin analogy a deriváty   farmakokinetika   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• citráty MeSH
• cyklické peptidy MeSH
• galium MeSH
• gallium 68-DOTA-lanreotide MeSH Prohlížeč
• gallium citrate MeSH Prohlížeč
• heterocyklické sloučeniny monocyklické MeSH
• koloidy MeSH
• radiofarmaka MeSH
• radioizotopy galia MeSH
• siderofory MeSH
• somatostatin MeSH