OBJECTIVE: Radiolabeled receptor-specific somatostatin analogs labeled with gamma- or beta-emitting radionuclides are useful for scintigraphic imaging and/or therapy of selected neuroendocrine tumors. However, significant renal uptake may result in radiotoxicological injury of the kidney and can limit clinical application of the agents. The aim of the study was to analyze renal handling, rate, and mechanism of renal accumulation of two somatostatin receptor-targeted peptides, [DOTA(0), Tyr(3), Thr(8)]-octreotide (DOTA-TATE) and [DOTA(0), 1-Nal(3)]-octreotide (DOTA-NOC), labeled with indium-111 using in vitro methods. METHODS: The perfused rat kidney and freshly isolated rat renal cells were used as experimental models. The perfusion was performed in a recirculation regimen at constant pressure with solution containing bovine albumin, erythrocytes, and a mixture of essential substrates. The renal cells were isolated from rat kidneys using two-phase collagenase perfusion. Accumulation studies were used to evaluate the renal uptake of the peptides and to compare their accumulation with that of passively or actively transported model drugs. The influence of selected inhibitors of receptor-mediated endocytosis and the inhibition of energy-dependent transport processes on the uptake were also investigated using isolated renal cells. RESULTS: The renal clearance of (111)In-DOTA-NOC in the perfused rat kidney was significantly lower than that of (111)In-DOTA-TATE. Reverse situation was found in the case of renal retention. Pretreatment of the perfused kidney with maleate markedly decreased the renal retention. (111)In-DOTA-NOC was accumulated in the isolated renal cells at a higher rate than (111)In-DOTA-TATE (ratio 3: 1). The uptake of the radiopeptides in renal cells was higher than the uptake of not only the passively transported sucrose but also actively transported and accumulated methylglucose. The rank order of potency to inhibit the uptake by active endocytosis was approximately aprotinin > maleate > lysine. The uptake of the radiopeptides in the renal cells was temperature dependent. CONCLUSIONS: Both in vitro methods showed a higher renal accumulation of (111)In-DOTA-NOC in comparison with (111)In-DOTA-TATE. The renal uptake was partly decreased by inhibitors of receptor-mediated endocytosis and by a block of energy-dependent processes. A significant participation of active transport processes in renal accumulation of the studied peptides was confirmed.

• MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• ledviny diagnostické zobrazování   metabolismus   MeSH
• metabolická clearance MeSH
• oktreotid analogy a deriváty   farmakokinetika   MeSH
• organokovové sloučeniny farmakokinetika   MeSH
• potkani Wistar MeSH
• radiofarmaka farmakokinetika   MeSH
• radioisotopová scintigrafie MeSH
• receptory somatostatinu metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita 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
• srovnávací studie MeSH
• Názvy látek
• 111In-DOTA-1-Nal(3)-octreotide MeSH Prohlížeč
• 111In-octreotate, DOTA(0)-Tyr(3)-Thr(8)- MeSH Prohlížeč
• oktreotid MeSH
• organokovové sloučeniny MeSH
• radiofarmaka MeSH
• receptory somatostatinu MeSH

Labelling of leucocytes with indium oxinate is currently used abroad. Labelled leucocytes are used mainly for the detection of inflammatory processes. The aim of the work was to test the binding capacity of the radiopharmaceutical preparation indium111 oxinate prepared in the Nuclear Research Institute of the Czechoslovak Academy of Science in Rez, its effect on the survival of leucocytes and its sterility. The authors' aim was also to use during separation of leucocytes Czechoslovak preparations to use this technique on a large scale in Czechoslovakia. The assembled results indicate a good quality of the used pharmaceutical preparation; the assessed values of the percentage of activity linked to leucocytes (72.85 +/- 14.95 closely after preparation and 93.74 +/- 5.91 24 hours after preparation) are consistent with data in the literature. The sterility of the solution and its influence on leucocyte vitality are also satisfactory. All work was done within the framework of preclinical tests of the mentioned preparation, as it was not yet approved for clinical use. In view of the assessed properties there are prerequisite conditions for its early use in clinical practice.

• MeSH
• leukocyty * MeSH
• lidé MeSH
• organokovové sloučeniny * MeSH
• oxychinolin analogy a deriváty   MeSH
• radioizotopy india MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• indium oxine MeSH Prohlížeč
• organokovové sloučeniny * MeSH
• oxychinolin MeSH
• radioizotopy india MeSH

5D3 is a new high-affinity murine monoclonal antibody specific for prostate-specific membrane antigen (PSMA). PSMA is a target for the imaging and therapy of prostate cancer. 111In-labeled antibodies have been used as surrogates for 177Lu/90Y-labeled therapeutics. We characterized 111In-DOTA-5D3 by SPECT/CT imaging, tissue biodistribution studies, and dosimetry. Methods: Radiolabeling, stability, cell uptake, and internalization of 111In-DOTA-5D3 were performed by established techniques. Biodistribution and SPECT imaging were done on male nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice bearing human PSMA(+) PC3 PIP and PSMA(-) PC3 flu prostate cancer xenografts on the upper right and left flanks, respectively, at 2, 24, 48, 72, and 192 h after injection. Biodistribution was also evaluated in tumor-free, healthy male CD-1 mice. Blocking studies were performed by coinjection of a 10-fold and 50-fold excess of 5D3 followed by biodistribution at 24 h to determine PSMA binding specificity. The absorbed radiation doses were calculated on the basis of murine biodistribution data, which were translated to a human adult man using organ weights as implemented in OLINDA/EXM. Results:111In-DOTA-5D3 was synthesized with specific activity of approximately 2.24 ± 0.74 MBq/μg (60.54 ± 20 μCi/μg). Distribution of 111In-DOTA-5D3 in PSMA(+) PC3 PIP tumor peaked at 24 h after injection and remained high until 72 h. Uptake in normal tissues, including the blood, spleen, liver, heart, and lungs, was highest at 2 h after injection. Coinjection of 111In-DOTA-5D3 with a 10- and 50-fold excess of nonradiolabeled antibody significantly reduced PSMA(+) PC3 PIP tumor and salivary gland uptake at 24 h but did not reduce uptake in kidneys and lacrimal glands. Significant clearance of 111In-DOTA-5D3 from all organs occurred at 192 h. The highest radiation dose was received by the liver (0.5 mGy/MBq), followed by the spleen and kidneys. Absorbed radiation doses to the salivary and lacrimal glands and bone marrow were low. Conclusion:111In-DOTA-5D3 is a new radiolabeled antibody for imaging and a surrogate for therapy of malignant tissues expressing PSMA.

• Klíčová slova
• PSMA, SPECT, SPECT/CT, immunoimaging, monoclonal antibody, prostate cancer,
• MeSH
• biologický transport MeSH
• glutamátkarboxypeptidasa II imunologie   MeSH
• heterocyklické sloučeniny monocyklické chemie   MeSH
• izotopové značení MeSH
• monoklonální protilátky chemie   imunologie   metabolismus   farmakokinetika   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• radioimunoterapie * MeSH
• radioizotopy india * MeSH
• SPECT/CT metody   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid MeSH Prohlížeč
• glutamátkarboxypeptidasa II MeSH
• heterocyklické sloučeniny monocyklické MeSH
• Indium-111 MeSH Prohlížeč
• monoklonální protilátky MeSH
• radioizotopy india * MeSH

BACKGROUND: Cholecystokinin receptor subtype 2 (CCK-2) is overexpressed in various tumours like medullary thyroid carcinomas and small cell lung cancer. Radiolabelled peptides that bind with high affinity and specificity to CCK-2 receptors, thus hold great potential for visualizing such tumours. METHODS: We compared four 111In labelled gastrin analogues, called minigastrins (MG), namely MG11, MG45, MG47 and MG48 linked to metal chelating DOTA in preclinical experiments. The radiolabelled peptides were tested for peptide binding in CCK-2 receptor-bearing cell line AR42J and for their pharmacokinetics in normal rats. RESULTS: The experiments suggest that all gastrin analogues had similar and relatively rapid internalization into AR42J cells. Binding to CCK-2 receptors in AR42J cells was saturable for all agents but there were some differences in receptor affinity. This biodistribution study in rats showed a rapid decrease in blood radioactivity, predominantly renal clearance and saturable uptake of the radiopharmaceutical and/or its metabolites in the CCK-2 receptor-positive stomach. Higher kidney accumulation of radioactivity was only found for 111In-DOTA-minigastrin 48. CONCLUSIONS: The data suggest that the 111In-DOTA-minigastrin analogues studied are promising candidates for the scintigraphy of CCK-2 receptor-expressing tumours; 111In-DOTA-MG47 and 111In-DOTA-MG11 are the most promising.

• MeSH
• gastriny farmakokinetika   farmakologie   MeSH
• heterocyklické sloučeniny monocyklické MeSH
• komplexní sloučeniny MeSH
• krysa rodu Rattus MeSH
• nádorové buněčné linie MeSH
• peptidy MeSH
• radiofarmaka MeSH
• receptor cholecystokininu B 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
• gastriny MeSH
• heterocyklické sloučeniny monocyklické MeSH
• indium-111-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid MeSH Prohlížeč
• komplexní sloučeniny MeSH
• minigastrin MeSH Prohlížeč
• peptidy MeSH
• radiofarmaka MeSH
• receptor cholecystokininu B MeSH

INTRODUCTION: Indium-111 when formulated as indium-111 oxine remains the gold standard for long term cell tracking, whereas radiometals for improved PET applications still have to be established. We here describe the on-cartridge formation of gallium-68, zirconium-89 and copper-64 complexes in small volumes suitable for cell labelling, including labelling of red blood cells (RBC) and white blood cells (WBC) and their biological evaluation in vivo. METHODS: Small volumes (1-2 mL) of tracers (oxine, tropolone) were directly prepared on an anion exchange cartridge (Sep-Pak QMA). Cells were radiolabelled and the labelling efficiency and efflux were evaluated. The in vivo biodistribution of copper-64-labelled WBC using [64Cu][Cu(oxinate)2] and [64Cu][Cu(tropolonate)2] was monitored in an infection and inflammation animal model using BALB/c mice. RESULTS: On-cartridge concentration of gallium-68, zirconium-89 and copper-64 enabled formation of oxine and tropolone tracers in small volumes with good yields (≥50%) and quality (extraction ≥90%). Prepared tracers radiolabelled the RBC comparable to indium-111 tracers and in vivo biodistribution of copper-64 labelled WBC showed clear accumulation of cells at the site of infection and inflammation. CONCLUSIONS: This on-cartridge preparation method enables simple formation of various PET tracers for cell radiolabelling. Zirconium-89 and copper-64 tracers radiolabelled cells with sufficient stability. Due to their longer half-life this approach could be promising for routine applications where longer evaluation periods for cell tracking are needed. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This novel approach for on-cartridge concentration and preparation of oxine and tropolone precursors with different positron emitters, in small volume and suitable pH, offers a versatile tool towards cell labelling for preclinical and clinical PET applications.

• Klíčová slova
• Cell labelling, Copper-64, Gallium-68, On-cartridge complex formation, PET, Zirconium-89,
• MeSH
• erytrocyty metabolismus   MeSH
• izotopové značení MeSH
• leukocyty metabolismus   MeSH
• myši MeSH
• PET/CT MeSH
• radiochemie přístrojové vybavení   MeSH
• radioizotopy galia chemie   metabolismus   MeSH
• radioizotopy mědi chemie   metabolismus   MeSH
• radionuklidy chemie   metabolismus   MeSH
• zirkonium chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Copper-64 MeSH Prohlížeč
• Gallium-68 MeSH Prohlížeč
• radioizotopy galia MeSH
• radioizotopy mědi MeSH
• radionuklidy MeSH
• Zirconium-89 MeSH Prohlížeč
• zirkonium MeSH

Polyamidoamine dendrimers (PAMAMs) of generations 1 (G1) and 4 (G4) were conjugated with a bifunctional pyridine-N-oxide DOTA analog, 10-[(4-carboxy-1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(4)do3a-py(NO-C)), through the pyridine-4-carboxylic acid group, and the conjugates were radiolabeled with indium-111. Reaction conditions for the radiolabelling were optimized. Both radiolabeled conjugates, G1-[(111)In(do3a-py(NO-C))] and G4-[(111)In(do3a-py(NO-C))], were kinetically stable for at least 48h after preparation; in the presence of competitive ligands, the radiochemical purity of the conjugates slightly decreased (4-7%) over the same time period. The preclinical pharmacokinetics of both agents were evaluated. Biodistribution and elimination in rats were more favorable for the G1-[(111)In(do3a-py(NO-C))] conjugate than G4-[(111)In(do3a-py(NO-C))] conjugate. However, the G1-[(111)In(do3a-py(NO-C))] conjugate was rapidly eliminated from the body, mainly through urine, while, significant and long-term radioactivity uptake in the liver and kidney was observed for the G4-[(111)In(do3a-py(NO-C))] conjugate.

• MeSH
• dendrimery chemie   farmakokinetika   MeSH
• heterocyklické sloučeniny monocyklické chemie   farmakokinetika   MeSH
• izotopové značení metody   MeSH
• krysa rodu Rattus MeSH
• nosiče léků chemie   farmakokinetika   MeSH
• potkani Wistar MeSH
• pyridiny chemie   farmakokinetika   MeSH
• radiofarmaka chemie   farmakokinetika   MeSH
• radioizotopy india chemie   farmakokinetika   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
• 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid MeSH Prohlížeč
• dendrimery MeSH
• heterocyklické sloučeniny monocyklické MeSH
• nosiče léků MeSH
• PAMAM Starburst MeSH Prohlížeč
• pyridine N-oxide MeSH Prohlížeč
• pyridiny MeSH
• radiofarmaka MeSH
• radioizotopy india MeSH

We have developed a radiolabeling strategy for synthetic polymers based on the formation of azo dye usable for both covalent and chelating labeling modalities under mild conditions. Poly[N-(2-hydroxypropyl)methacrylamide] and poly(N-isopropyl acrylamide) were used as model polymers. N-methacryloyl tyrosinamide was introduced into the polymers and the phenolic moiety was then reacted with diazotized chelator precursors. The conjugates were radiolabeled with both the covalently bound (iodine-125) and chelated (indium-111) radionuclides in high yields and sufficient in vitro stability of the labels was proven.

• MeSH
• azosloučeniny chemie   MeSH
• izotopové značení metody   MeSH
• polymery chemie   MeSH
• radionuklidy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azosloučeniny MeSH
• polymery MeSH
• radionuklidy MeSH

Immunoscintigraphic methods present a great step forward in non-invasive diagnostics. They contribute not only in tumor diagnostic where monoclonal antibodies against tumorous antigens (TAG 72, CEA) are used but also in the sphere of inflammation diagnostic with the use of monoclonal antibody BW 250/183 which is bound onto non-specific cross reacting antigen NCA 95 of granulocytes. Another sphere of interest is the detection of heart muscle damage with the use of monoclonal antibody against myosin and detection of venous thrombosis with the use of monoclonal antibody against fibrin. Monoclonal antibodies are labelled with indium 111 or technecium 99m.

• MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• radioimunodetekce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• monoklonální protilátky MeSH

Non-steroidal anti-inflammatory drug (NSAIDs) induced enteropathy represents an important complication of one of the most commonly used drugs worldwide. Due to previous diagnostics difficulties the real prevalence of this disease was underestimated for a long time. The pathogenesis of NSAID-enteropathy is more multifactorial and complex than formerly assumed but has still not been fully uncovered. A combination of the local and systemic effect plays an important role in pathogenesis. Thanks to novel enteroscopy methods (wireless capsule endoscopy, double balloon enteroscopy), small bowel lesions are described in a substantial section of NSAID users although most are clinically asymptomatic. The other non-invasive tests (small bowel permeability, faecal calprotectin, scintigraphy using faecal excretion of 111-indium-labelled leukocytes etc.) proposed for diagnostics are not generally used in clinical practice, mainly because of their non-specificity. Despite intensive research into possible treatment, the main measure for patients with NSAID-enteropathy is still withdrawal of NSAIDs. Double balloon enteroscopy plays an important role in the treatment of complications (bleeding, strictures).

• MeSH
• antiflogistika nesteroidní škodlivé účinky   MeSH
• Aspirin škodlivé účinky   MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• nemoci střev chemicky indukované   diagnóza   patologie   MeSH
• tenké střevo účinky léků   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• Aspirin MeSH

Electrons confined within the 2D layer of metals grown on silicon substrates exhibit exotic properties due to strong correlation effects. Their properties, such as their 2D superconductivity, have been frequently subjected to possible tuning by doping using charge transfer from adsorbed layers. Doping relies on adding electrons or holes to the system and the resulting shift of the Fermi level EF in the otherwise robust surface electronic structure. This strategy has not been sufficiently controlled in the case of an indium double layer grown on the Si(111) surface. This study provides an alternative approach relying on spatially periodic modification of the surface electronic structure of the 2D metal. Derivatives of diketopyrrolopyrroles (DPP) are used for the growth of perfectly ordered 1D-like molecular superstructures on top of the In double layer, imaged by scanning tunneling microscopy. The integral changes of electronic structure are measured by angle-resolved photoelectron spectroscopy and density functional theory calculations show local modification of the surface states near EF by the adsorbed molecules. This study demonstrates that the surface electronic states can be controllably patterned, using a proper bonding scheme. It is anticipated that the combination of the original 2D superconductor and the 1D-like patterning will motivate further research.

• Publikační typ
• časopisecké články MeSH