Search

Dendritic cell-based immunotherapy, in which the antigen is effectively delivered to dendritic cells and then the dendritic cells stimulated by the antigen migrate to draining lymph nodes (DLNs) to...

This work reports the synthesis, radiolabeling and imaging studies of iodine-124 labeled peptide modified gold nanoclusters (AuNCs) as positron emission tomography (PET) tracer for lung cancer. The novel modified Au nanoclusters were successfully synthesized by conjugation of tumortargeting peptide luteinizing hormone releasing hormone (LHRH) to human serum albumin (HAS) as a scaffold, resulting in 73% labeling yield of 124I-LHRH-HSA AuNCs. After rapid purification, the radiochemical purity was above 98%. Dynamic PET study in normal rats showed high liver accumulation and rapid lung clearance. Both the PET and fluorescence imaging in A549 xenografted tumor model demonstrated certain amount of tumor uptake. In orthotopic lung cancer model, the tumor sites could be clearly visualized between 2 to 5 hours in PET images. The higher radioactivity concentration in the left lung which inoculated orthotopic tumor than right lung also exhibited the targeting properties. The biological properties of this iodine-124 labeled nanoclusters afford potential applications for early diagnosis of lung cancer with PET.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.

Traditional photodynamic therapy (PDT) requires external light excitation to produce reactive oxygen species (ROSs) for the treatment of tumors. Due to problems of light penetration, traditional PDT is limited by the location and depth of the tumor. In this study, we rationally designed and constructed a novel strategy to amplify the therapeutic effect of PDT. We prepared a chlorin-lipid nanovesicle based on the conjugates of chlorin e6 (Ce 6) and phospholipids, with the surface conjugating the aptamer for lung cancer targeting, GLT21.T. 131I-labeled bovine serum albumin (131I-BSA) was loaded into the chlorin-lipid nanovesicle cavity (131I-BSA@LCN-Apt). 131I not only plays a role in radiotherapy, but its Cerenkov radiation (CR), as an internal light source, can also stimulate Ce6 to produce ROSs without external light excitation. The in vitro and in vivo therapeutic effects in subcutaneous lung tumor models and orthotopic lung tumor models indicated that 131I-BSA@LCN-Apt produced a powerful anti-tumor effect through synergistic radiotherapy and CR-PDT, which almost caused complete tumor growth regression. After treatment, the survival time of the mice was significantly prolonged. During the treatment, no obvious side effects were found by histopathology of important organs, hematology and biochemistry analysis except the decrease of the white blood cell count (WBC). The study provides a major tool for deep-seated tumors to obtain amplified therapeutic effects by synergistic radiotherapy and CR-PDT without the use of any external light source.

This work reports the synthesis, radiolabeling, and biological studies of 99m Tc-diethylene triamine pentaacetic acid (DTPA)-colchicine dimer in tumor-bearing mice. The novel colchicine dimer was successfully synthesized by conjugation of DTPA to 2 colchicine biomolecules. The ligand could be labeled by 99m Tc in high yield to get 99m Tc-DTPA-colchicine dimer, which was hydrophilic and stable at room temperature. Biodistribution and imaging studies in tumor-bearing mice showed that 99m Tc-DTPA-colchicine dimer accumulated in the tumor with improved uptake and retention. The results indicate the need for synthetic modification of the parent colchicine derivative and the 99m Tc-chelate with a view to improve the tumor-targeting efficacy and in vivo kinetic profiles.

Melphalan (MFL) is a typical nitrogen mustard for the treatment of many types of cancer. For the purpose to develop novel 99m Tc-labeled tumor imaging agents with SPECT, MFL was directly labeled by 99m Tc using diethylene triamine pentacetate acid (DTPA) as bifunctional chelating agent. The novel ligands were successfully synthesized by conjugation of DTPA to MFL to get monosubstituted DTPA-MFL and bis-substituted DTPA-2MFL. Radiolabeling was performed in high yield to get 99m Tc-DTPA-MFL and 99m Tc-DTPA-2MFL, respectively, which were hydrophilic and stable at room temperature. The high initial tumor uptake with retention, good tumor/muscle ratios, and satisfactory scintigraphic images suggested the potential of 99m Tc-DTPA-MFL and 99m Tc-DTPA-2MFL for tumor imaging. However, the slow normal tissue clearance would be a great obstacle. Further modification on the linker and/or 99m Tc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.

This work highlights the superiority of the surface-radiolabeling strategy over the core-labeling strategy in the assembly of radioactive iron oxide nanoparticle (IONP)-based nanocomposites for use in multimodal imaging and targeted therapy. It also implies a possible overestimation of the labeling stability in previous studies and points out directions for further optimization.

A wormlike micelle templated attachment growth approach for the preparation of mono- and bi-metallic nanochain networks is reported. Zwitterionic wormlike micelles with PtCl62− and PdCl42− counterions were fabricated for the first time as soft-templates. A possible soft-template assisted attachment-based growth mechanism for nanochain formation is proposed for the morphological replica process. The present strategy was further extended to synthesize alloyed noble-metal such as Pt–Au, Pd–Au, and Pt–Pd nanochain networks. The results presented may provide inspirations and strategies for the fabrication of noble metal nanostructures with adjustable structures and constituents through soft templated attachment growth.

This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of Tc-99m(CO)(3)-labeled pegylated (PEG) 2-nitroimidazoles for tumor hypoxia imaging. The novel 2-nitroimidazole derivatives were successfully synthesized by conjugation of tridendate chelators to 2-nitroimidazole via PEG(3) linker. Radiolabeling was performed in high yield with [Tc-99m(CO)(3)](+) core to get cationic [Tc-99m(CO)(3)(BPA-PEG(3)-NIM)](+), neutral [Tc-99m(CO)(3)(AOPA-PEG(3)-NIM)] and anionic [Tc-99m(CO)(3)(IDA-PEG(3)-NIM)](-) respectively, all of which were hydrophilic and stable at room temperature. Biodistribution studies in tumor-bearing mice showed that Tc-99m(CO)(3)-labeled pegylated 2-nitroimidazoles accumulated in the tumor with low uptake. Tc-99m-chelate and charge had significant impact on partition coefficient, radiotracer tumor uptake and pharmacokinetic properties. The results indicate the need for synthetic modification of the parent 2-nitroimidazole derivatives and the Tc-99m-chelate with a view to improve the tumor targeting efficacy and in vivo kinetic profiles.

In order to develop a novel 99mTc-labeled folate based SPECT radiotracer with an optimized pharmacokinetic profile for the folate receptor (FR) positive tumor imaging, a folate conjugate, HYNIC-PEG2-FA, was designed, synthesized and radiolabeled with 99mTc using tricine/diphenylphosphinobenzene-3-sulfonic acid sodium (TPPMS), tricine/trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS), and ethylenediamine-N,N′-diacetic acid (EDDA) as coligands. 99mTc(HYNIC-PEG2-FA)(tricine/TPPTS), 4, 99mTc(HYNIC-PEG2-FA)(tricine/TPPMS), 5 and 99mTc(HYNIC-PEG2-FA)(EDDA), 6, were obtained respectively. All of them were stable in saline and mouse plasma for 6 h, and displayed high specific binding in the FR-positive KB cell line in vitro. Among them, complex 4 exhibited a higher tumor uptake (11.35 ± 0.67 ID% g−1 at 2 h p.i.) and more rapid clearance from the liver, lungs, blood, muscle and other non-target organs than 99mTc (HYNIC-NHHN-FA)(tricine/TPPTS), which we reported before. Small animal SPECT/CT imaging studies in FR-positive KB tumor models showed that the tumor could be clearly visualized at 120 min p.i., suggesting its potential as a promising folate receptor targeting agent for tumor imaging.

Diethylenetriaminepentaacetic acid neolactosyl human serum albumin (DTPA-LSA) was prepared and labeled with technetium-99m. The labeling conditions of Tc-99m-DTPA-LSA were optimized, and lyophilized kit was developed for instant preparing of Tc-99m-DTPA-LSA. Tc-99m-DTPA-LSA showed high liver uptake in normal mice (> 96% ID/g at 5 min after injection), and it could be blocked significantly by pre-injecting free neogalactosylalbumin (NGA). Single photon emission computed tomography (SPECT) study was performed in normal Japanese White rabbits and SPECT images with high quality were obtained at 15, 30, 60, and 120 min after injection of the radiotracer. The promising biological properties of Tc-99m-DTPA-LSA combined with the development of reliable and instant lyophilized DTPA-LSA kit afford the opportunity of hepatic receptor imaging for routine clinical assessment of hepatic function. (c) 2012 Elsevier Ltd. All rights reserved.

The chlorambucil L-histidine conjugate was synthesized and radiolabeled with [Tc-99m(CO)(3)](+) core to form the Tc-99m(CO)(3)(His-CB) complex. The radiochemical purity of the complex was over 90%. It had good hydrophilicity and was stable at room temperature. The high initial tumor uptake with certain retention, fast clearance from background, good tumor/non-tumor ratios and satisfactory scintigraphic images highlighted the potential of Tc-99m(CO)(3)(His-CB) as a tumor imaging agent. (C) 2012 Elsevier Ltd. All rights reserved.

Three chemical modification methods of carboxymethylation, quaternization and hydroxypropylation were used to synthesize water-soluble chitosan derivatives. In order to study the feasibility of these chitosan derivatives as backbones of nuclear imaging agents, folic acid (FA) and Technetium-99m were introduced onto the water-soluble chitosan chains. The bifunctional chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to the folate grafted chitosan derivatives for chelating with radionuclides such as (64)Cu and (68)Ga. The structures of these new ligands were characterized with multiple methods. The solubility and stability of the (99m)Tc-complexes were both favorable. Further study of their radiochemical and biological properties will be performed to evaluate the usefulness of these water-soluble chitosan derivatives for nuclear imaging agent design.

The (2-methoxyphenyl) piperazine (MPP) was selected as the functional group and conjugated to dithiocarbamate through different spacers. A series of new MPP derivatives (MPPnDTC, n = 2–6) were synthesized and radiolabelled with 99mTc-nitrido core or 99mTc-tricarboxyl core as potential 5-HT1A receptor imaging agents. All the six 99mTc-labelled complexes were lipophilic and neutral. Biodistribution results showed that those radiotracers had moderate initial brain and hippocampus uptake. There have no significant relation was observed between the biological properties of these tracers with the length of its carbon chain. The radioactivity concentrations of hippocampus of 99mTcN-MPP2DTC, 99mTcN-MPP3DTC, 99mTcN-MPP4DTC, 99mTcN-MPP5DTC, 99mTcN-MPP6DTC and 99mTc(CO)3-MPP3DTC at 2 min post-injection time (p.i.) were 0.43, 1.15, 0.99, 1.04, 1.13 and 0.83 %ID/g, respectively.

Rare-earth-based nanoparticles have attracted increasing attention for their unique optical and magnetic properties. However, their application in bioimaging has been limited to photoluminescence bioimaging and magnetic resonance imaging. To facilitate their use in other bioimaging techniques, we developed a simple, rapid, efficient and general synthesis strategy for (18)F-labeled rare-earth nanoparticles through a facile inorganic reaction between rare-earth cations and fluoride ions. The (18)F-labeling process based on rare-earth elements was achieved efficiently in water at room temperature with an (18)F-labeling yield of >90% and completed within 5 min, with only simple purification by aqueous washing and centrifugation, and without the use of organic agents. The effectiveness of (18)F-labeled rare-earth nanoparticles was further evaluated by positron emission tomography (PET) imaging of their in vivo distribution and application in lymph monitoring. In addition, this strategy is proposed for the creation of a dual-model bioimaging technique, combining upconversion luminescence bioimaging and PET imaging.

A novel bifunctional coupling agents-biomolecular compound DMP-NGA was prepared by coupling the SATP with galactosyl-neoglycoalbumin (NGA). The DMP-NGA was labeled with technetium-99 m, and the radiochemical purity in excess of 98% after purified with HPLC. In vivo biodistribution showed that 99m Tc-DMP-NGA had very high initial liver uptake with good retention. The liver accumulated 99.35±9.77%, 74.25±3.03%, 52.47±7.58% of the injected dose per gram at 5, 30 and 120 min after injection, respectively. It had relative higher initial liver uptake and much lower blood uptake than that of 99m Tc-GSA. The liver/blood ratio reached 83.4 at 30 min post-injection, while the ratio of liver/kidney was 14.4. The uptakes in other organs in the abdomen were also slightly low. In addition, the hepatic uptake of 99m Tc-DMP-NGA was blocked by preinjecting free GSA as blocking agent. The result indicates that 99m Tc-DMP-NGA has specific binding to ASGP receptor. Images acquired with Kodak In-Vivo Imaging System FX Pro showed significant difference before and after inhibition. The promising biological properties of 99m Tc-DMP-NGA afford potential applications in liver receptor imaging for assessment of hepatocyte function.

This study reports the synthesis and characterization of N-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl-4-[(18)F]fluorobenzamide ([(18)F]MPP3F). The total reaction time for [(18)F]MPP3F, including final high-performance liquid chromatography purification, was about 3h. Typical decay-corrected radiochemical yield was 18.4+/-3.1%. The radiochemical purity was98%. Biodistribution in mice showed that [(18)F]MPP3F is a potential brain imaging agent for positron emission tomography. The brain uptake of [(18)F]MPP3F was 6.59+/-0.77% Injected Dose/g at 2 min post-injection time. A brain-to-blood ratio of 3.67 was reached at 15 min after injection.

In order to study the extraction pattern of protactinium in different types of extracting agents and compare the similarity of patterns of extraction with dubnium and thereby unraveling its chemistry, solvent extraction of protactinium(V) with methyl-iso-butyl carbinol (MIBC) and methyl-iso-butyl ketone (MIBK) was studied using 233Pa as a radiotracer. The extraction efficiencies of Pa were determined as a function of shaking time, concentrations of mineral acids, and extractant concentrations using the two extractants. The results show that MIBK is more suitable for the extraction of protactinium than MIBC in benzene. Furthermore, the effect of the F anion is also discussed.

The neutron-rich target-like isotope 236Th has been produced in the 238U-2p multinucleon transfer reaction between a 60 MeV/u 18O beam and natural 238U targets. The activities of thorium were determined after radiochemical separation of Th from the mixture of uranium and reaction products. The 236Th isotope was identified by the characteristic γ-rays of 642.2, 687.6 and 229.6 keV. The production cross section of 236Th was determined to be 250±50 μb.

Solvent extraction of protactinium with tri-iso-octyl-amine (TIOA) in xylene, benzene, carbon tetrachloride and chloroform from HCl, HF, HNO3, HClO4 and H2SO4 media was studied using 233Pa as a radiotracer. The extraction efficiencies of protactinium were determined as a function of shaking time, concentrations of mineral acids in aqueous phase, extractant concentrations and diluents in organic phase. The extraction mechanism was discussed. The results show that the extracted species in the organic phase is [(R3N−H)nPa(OH)xCl y 5−x−y ].

The goal of this study is to develop a novel 5-HT 1A receptor imaging agent. 4-[(2-methoxyphenyl)piperazin-1-yl]-dithioformate (MPPDTF) was labeled with 99m Tc-tricarbonyl core via dithioformate moiety in high yield (>96% by HPLC). 99m Tc(CO) 3 –MPPDTF is a neutral and lipophilic complex, which was confirmed by paper electrophoresis and octanol/water partition coefficient ( P =27.0±1.4, n =3), respectively. In vivo biodistribution indicated that this complex had moderate brain uptake (0.53±0.10% ID/g at 5 min and 0.42±0.02% ID/g at 120 min) and good retention (about 80% of the activity was retained in the brain at 120 min post-injection). Regional brain distribution study showed that hippocampus, where the 5-HT 1A receptor density is high, had the highest uptake (0.60±0.02% ID/g at 5 min p.i.) and the cerebellum, where the 5-HT 1A receptor density is low, had the lowest uptake (0.10±0.02% ID/g at 5 min p.i.). After blocking with 8-OH-DPAT, the hippocampus uptake was decreased obviously while the cerebellum uptake was increased slightly. This result indicates that 99m Tc(CO) 3 –MPPDTF complex has specific binding to 5-HT 1A receptor.

The extraction of protactinium with Aliquat 336 (methyl-tri-caprylyl ammonium chloride) in toluene, cyclohexane and chloroform from HCl, HNO3, H2SO4, HClO4, HF and mixed HCl-HF media was investigated by radioactive tracer technique. Distribution ratios of protactinium between the aqueous solution and the organic phase were determined as a function of shaking time, concentrations of acid in aqueous solution phase, extractant concentration and type of diluents in the organic phase. Aliquat 336 can almost quantitatively extract protactinium from strong HCl solution. At the same time, small amounts of HF in HCl solutions have a strong effect on Pa distribution.

Osmium isotope, 197Os, produced with 14 MeV neutrons through the reaction of 198Pt(n,2p)197Os, has been identified and its decay properties have been studied with a g(X) spectroscopic method. The ten new g-rays of 41.2, 50.7, 196.8, 199.6, 223.9, 233.1, 250.2, 342.1, 403.6, and 406.4 keV assigned to the decay of 197Os were observed. The half-life of 197Os has been determined as 2.8±0.6 minutes. A partial decay scheme of 197Os was proposed.

Lipophilic cations such as phosphonium salts can accumulate in mitochondria of heart in response to the negative inner-transmembrane potentials. Two phosphonium salts [(18)F]FMBTP and [(18)F]mFMBTP were prepared and evaluated as potential myocardial perfusion imaging (MPI) agents in this study. The cations were radiolabeled via a simplified one-pot method starting from [(18)F]fluoride and followed by physicochemical property tests, in vitro cellular uptake assay, ex vivo mouse biodistribution, and in vivo rat microPET imaging. The total radiosynthesis time was less than 60 min including HPLC purification. The [(18)F] labeled compounds were obtained in high radiolabeling yield (∼50%) and good radiochemical purity (>99%). Both compounds were electropositive, and their log P values at pH 7.4 were 1.16 ± 0.003 (n = 3) and 1.05 ± 0.01 (n = 3), respectively. Both [(18)F]FMBTP and [(18)F]mFMBTP had high heart uptake (25.24 ± 2.97% ID/g and 31.02 ± 0.33% ID/g at 5 min postinjection (p.i.)) in mice with good retention (28.99 ± 3.54% ID/g and 26.82 ± 3.46% ID/g at 120 min p.i.). From the PET images in rats, the cations exhibited high myocardium uptake and fast clearance from liver and small intestine to give high-contrast images across all time points. These phosphonium cations were radiosynthesized via a highly efficient one-pot procedure for potential MPI offering high heart accumulation and rapid nontarget clearance.

Poly(vinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide) (PVLA) can be specifically internalized by hepatocytes via the asialoglycoprotein receptor. In this study, we synthesized and characterized galactose-carrying copolymers with hydrazinonicotinamide chains as bifunctional groups to radiolabel PVLA with 99mTc for SPECT targeting specific hepatocytes. Methods: Poly(N-p-vinylbenzyl-[O-β-D-galactopyranosyl-(1→4)-D-gluconamide]-co-N-p-vinylbenzyl-6-[2-(4-dimethylamino)benzaldehydehydrazono]nicotinate) (P(VLA-co-VNI)) was first prepared via copolymerization of N-p-vinylbenzyl-O-β-D-galactopyranosyl-D-gluconamide with 5% (mol) of N-p-vinylbenzyl-(4-dimethylaminobenzaldehyde hydrazono)nicotinamide. The copolymer was labeled with 99mTc using tricine as a coligand. Then 99mTc[P(VLA-co-VNI)](tricine)2 was evaluated by in vivo metabolic stability and biodistribution in normal mice. SPECT was performed in normal New Zealand White rabbits and rabbits with liver cancer. Results:99mTc[P(VLA-co-VNI)](tricine)2 was prepared in high labeling yield (>95%) and radiochemical purity (>99%), with good stability. The results of biodistribution in mice demonstrated that the liver uptake was 125.33 ± 10.99 percentage injected dose per gram at 10 min after injection and could be blocked significantly by preinjecting free neogalactosylalbumin or P(VLA-co-VNI). SPECT images with high quality were obtained at 15, 30, 60, and 120 min after injection of the radiotracer. Significant radioactivity defect was observed in the liver cancer model. Conclusion: The bifunctional coupling agent hydrazinonicotinamide was introduced to PVLA via copolymerization and labeled with 99mTc. The promising biologic properties of 99mTc[P(VLA-co-VNI)](tricine)2 afford potential applications for the assessment of hepatocyte function in the future.

The feasibility of chitosan (CS) as a backbone for the design of (99m)Tc-labeled targeting agent was evaluated in this study. Chitosan-folate conjugate (CSFA) and chitosan-folate dithiocarbamate (CSFADTC) were synthesized, characterized and radiolabeled with (99m)Tc as model compounds for folate-receptor (FR) targeting. (99m)Tc-complexes were prepared with high radiochemical purity and high stability. The hydrophilicities of these (99m)Tc-complexes were determined by partition coefficient experiments. The results of biodistribution in normal mice showed that the folic-acid modified agents ((99m)Tc-CSFA and (99m)TcN-CSFADTC) had obviously higher uptake in FR-positive kidney and much lower liver and spleen uptakes than that of non-folic-acid modified (99m)Tc-agent, and the kidney uptakes of FA-modified agents could be blocked significantly by the corresponding cold ligand. Furthermore in vitro and in vivo specific studies will be done in cell line and tumor bearing mice to confirm the usefulness of this chitosan backbone for FR targeting agent design.

Galactosylated chitosan (GC) was prepared by reacting lactobionic acid with water-soluble chitosan. GC was labeled with fluorine-18 by conjugation with N-succinimidyl-4-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, [(18)F]FB-GC was obtained with high radiochemical purity (>97%) determined by radio-HPLC. The total reaction time for [(18)F]FB-GC was about 150 min. Typical decay-corrected radiochemical yield was about 4-8%. Ex vivo biodistribution in normal mice showed that [(18)F]FB-GC had moderate activity accumulation in liver with very good retention (11.13+/-1.63, 10.97+/-1.90 and 10.77+/-0.95%ID/g at 10, 60, 120 min after injection, respectively). The other tissues except kidney showed relative low radioactivity accumulation. The high liver/background ratio affords promising biological properties to get clear images. The specific binding of this radiotracer to the ASGP receptor was confirmed by blocking experiment in mice. Compared with the non-blocking group the hepatic uptake of [(18)F]FB-GC significantly declined in all selected time points. The better liver retention properties of [(18)F]FB-GC than that of albumin based imaging agents may improve imaging quality and simplify pharmacokinetic model of liver function in the future application with PET imaging.

Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor, is well correlated with blood flow. Based on the synthesis and characterization of pyridaben analogue 2- tert -butyl-5-[2-(2-[ 18 F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2 H -pyridazin-3-one ([ 18 F]FP2OP), this study assessed its potential to be developed as myocardial perfusion imaging (MPI) agent. Methods : The tosylate labeling precursor 2-(2-(4-( tert -butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)benzyloxy)ethoxy)ethyl ester (OTs-P2OP) and the nonradioactive 2- tert -butyl-5-[2-(2-[ 19 F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2 H -pyridazin-3-one ([ 19 F]FP2OP) were synthesized and characterized by IR, 1 H NMR, 13 C NMR and MS analysis. By substituting tosyl of precursor OTs-P2OP with 18 F, the radiolabeled complex [ 18 F]FP2OP was prepared and further evaluated for its in vitro physicochemical properties, in vivo biodistribution, the metabolic stability in mice, ex vivo autoradiography and cardiac PET/CT imaging. Results : Starting with [ 18 F]F − Kryptofix 2.2.2./K 2 CO 3 solution, the total reaction time for [ 18 F]FP2OP was about 100 min, with final high-performance liquid chromatography purification included. Typical decay-corrected radiochemical yield stayed at 41 ± 5.3%, the radiochemical purity, 98% or more. Biodistribution in mice showed that the heart uptake of [ 18 F]FP2OP was 41.90 ± 4.52%ID/g at 2 min post-injection time, when the ratio of heart/liver, heart/lung and heart/blood reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further produced by metabolized [ 18 F]FP2OP in blood and urine at 30 min. Ex vivo autoradiography demonstrates that [ 18 F]FP2OP may have high affinity with MC-I and that can be blocked by [ 19 F]FP2OP or rotenone (a known MC-I inhibitor). Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min post-injection time with high quality. Conclusion : [ 18 F]FP2OP was synthesized with high radiochemical yield. The promising biological properties of [ 18 F]FP2OP suggest high potential as MPI agent for positron emission tomography in the future.

Asialoglycoprotein receptors (ASGP-R) are well known to exist on the mammalian liver, situate on the surface of hepatocyte membrane. Quantitative imaging of asialoglycoprotein receptors could estimate the function of the liver. 99m Tc labeled galactosyl-neoglycoalbumin (NGA) and diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) have been developed for SPECT imaging and clinical used in Japan. In this study, we labeled the NGA with 18 F to get a novel PET tracer [ 18 F]FNGA and evaluated its hepatic-targeting efficacy and pharmacokinetics. Methods : NGA was labeled with 18 F by conjugation with N -succinimidyl-4- 18 F-fluorobenzoate ([ 18 F]SFB) under a slightly basic condition. The in vivo metabolic stability of [ 18 F]FNGA was determined. Ex vivo biodistribution of [ 18 F]FNGA and blocking experiment was investigated in normal mice. MicroPET images were acquired in rat with and without block at 5 min and 15 min after injection of the radiotracer (3.7 MBq/rat), respectively. Results : Starting with 18 F − Kryptofix 2.2.2./K 2 CO 3 solution, the total reaction time for [ 18 F]FNGA is about 150 min. Typical decay-corrected radiochemical yield is about 8–10%. After rapid purified with HiTrap desalting column, the radiochemical purity of [ 18 F]FNGA was more than 99% determined by radio-HPLC. [ 18 F]FNGA was metabolized to produce [ 18 F]FB-Lys in urine at 30 min. Ex vivo biodistribution in mice showed that the liver accumulated 79.18 ± 7.17% and 13.85 ± 3.10% of the injected dose per gram at 5 and 30 min after injection, respectively. In addition, the hepatic uptake of [ 18 F]FNGA was blocked by pre-injecting free NGA as blocking agent (18.55 ± 2.63%ID/g at 5 min pi), indicating the specific binding to ASGP receptor. MicroPET study obtained quality images of rat at 5 and 15 min post-injection. Conclusion : The novel ASGP receptor tracer [ 18 F]FNGA was synthesized with high radiochemical yield. The promising biological properties of [ 18 F]FNGA afford potential applications for assessment of hepatocyte function in the future. It may provide quantitative information and better resolution which particularly help to the liver surgery.

Fullerenes (C60) and metallofullerenes (Gd@C82) have similar chemical structure, but the bio-effects of both fullerene-based materials are distinct in vivo. Tracking organic carbon-based materials such as C60 and Gd@C82 is difficult in vivo due to the high content of carbon element in the living tissues themselves. In this study, the biodistribution and metabolism of fullerenes (C60 and Gd@C82) radiolabeled with (64)Cu were observed by positron emission tomography (PET). (64)Cu-C60 and (64)Cu-Gd@C82 were prepared using 1, 4, 7, 10-tetrakis (carbamoylmethyl)-1, 4, 7, 10-tetra-azacyclodo-decanes grafted on carbon cages as a chelator for (64)Cu, and were obtained rapidly with high radiochemical yield (≥90%). The new radio-conjugates were evaluated in vivo in the normal mouse model and tissue distribution by small animal PET/CT imaging and histology was carried out. The PET imaging, the biodistribution and the excretion of C60 and Gd@C82 indicated that C60 samples have higher blood retention and lower renal clearance than the Gd@C82 samples in vivo and suggested that the differences in metabolism and distribution in vivo were caused by the structural differences of the groups on the fullerene cages though there is chemical similarity between C60 and Gd@C82.