RESUMO
Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [18F][Gd(FL1)], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [18F][Gd(FL1)] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [18F][Gd(FL1)] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for improved diagnostic accuracy.
RESUMO
The cross-sections of the natTi(3He,x)48V,48Cr and the 165Ho(3He,xn)166,165,163Tm reactions were measured from the threshold to 47â¯MeV using well-established method of stacked-foil activation and off-line γ-ray spectrometry. The 3He-ion induced nuclear reaction cross-sections on 165Ho were measured for the first time. Their comparison with the prediction adopted from the TENDL-2017 library revealed significant difference. Thick target yields deduced from the experimental data are provided.
RESUMO
Human carbonic anhydrase IX is a membrane enzyme that is significantly expressed in some types of cancer cells, while copper radioisotopes offer wide range of diagnostic, therapeutic and theranostic properties. The work was focused on a new approach to the labelling of antibody IgG M75 for epitope human carbonic anhydrase IX with copper radioisotopes 61Cu and 64Cu and its in vivo testing in mice with inoculated colorectal cancer. Monoclonal antibody IgG M75 for epitope human carbonic anhydrase IX was successfully conjugated with copper-specific chelator "phosphinate" and labelled with 61Cu and 64Cu The obtained molecule has considerable potential as a radioimmuno pharmaceutical suitable for imaging of tumours expressing carbonic anhydrase IX by positron emission tomography (PET).
Assuntos
Anticorpos Monoclonais/química , Antígenos de Neoplasias/imunologia , Anidrase Carbônica IX/imunologia , Radioisótopos de Cobre/química , Animais , Anticorpos Monoclonais/farmacocinética , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/enzimologia , Radioisótopos de Cobre/farmacocinética , Células HT29 , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Imunoglobulina G/química , Masculino , Camundongos , Camundongos Nus , Tomografia por Emissão de Pósitrons , Radioimunodetecção , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
Specific oncology diagnostics requires new types of the selective radiopharmaceuticals, particularly those suitable for the molecular PET imaging. The aim of this work is to present a new, specific PET-immunodiagnostic radiopharmaceutical based on the monoclonal antibody IgG M75 targeting human carbonic anhydrase IX labelled with 64Cu (T½ = 12.70h) and its in vitro and in vivo evaluation. The antibody IgG M75 was conjugated with a non-commercial copper-specific chelator "phosphinate" and then labelled with the positron emitter 64Cu. Stability of the labelled conjugated was tested in human serum. The immunoreactivity of the labelled conjugate was evaluated in vitro on a suitable cell cultures of the colorectal carcinoma (HT-29) and its imaging properties were estimated in vivo on a mouse model with inoculated colorectal carcinoma HT-29 imaged on a µPET/CT. The tested radioimmunoconjugate was obtained in a specific activity of 0.25-0.5 MBq/µg. In vitro uptake experiments revealed specific binding to the HT-29 cells (45 ± 2.8% of the total added activity) and the measured KD value was found to be 9.2nM. Imaging clearly demonstrated significant uptake of the labelled monoclonal antibody in the tumour at 18h post administration. The radioimmunoconjugate 64Cu-PS-IgG M75 seems to be a suitable candidate for PET diagnostics of hypoxic tumours expressing human carbonic anhydrase IX.
Assuntos
Anticorpos Monoclonais/farmacologia , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/farmacologia , Anidrase Carbônica IX/antagonistas & inibidores , Anidrase Carbônica IX/imunologia , Radioisótopos de Cobre/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Animais , Anticorpos Monoclonais/farmacocinética , Antineoplásicos Imunológicos/farmacocinética , Transporte Biológico Ativo , Radioisótopos de Cobre/farmacocinética , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Células HT29 , Humanos , Imunoconjugados/farmacocinética , Imunoconjugados/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Nus , Células NIH 3T3 , Neoplasias/diagnóstico por imagem , Neoplasias/enzimologia , Ácidos Fosfínicos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
A novel approach for preparation of ultra-bright fluorescent nanodiamonds (fNDs) was developed and the thermal and kinetic optimum of NV center formation was identified. Combined with a new oxidation method, this approach enabled preparation of particles that were roughly one order of magnitude brighter than particles prepared with commonly used procedures.
Assuntos
Fluorescência , Corantes Fluorescentes/síntese química , Nanodiamantes/química , Corantes Fluorescentes/efeitos da radiação , Nanodiamantes/efeitos da radiação , Tamanho da Partícula , Prótons , Coloração e Rotulagem/instrumentação , Coloração e Rotulagem/métodosRESUMO
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, Rez. 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.