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Y Arano

Publications and source records attributed to Y Arano.

At least 73 records · Page 4Linked to original sources
PubMed1992

62Cu-labeled bifunctional radiopharmaceuticals with metabolizable ester groups.

Generator-produced positron emitting 62Cu-labeled bifunctional radiopharmaceuticals with metabolizable ester groups were synthesized and evaluated for their bifunctionality: the Cu chelating ability and the biochemical reactivity of the ester groups. In vitro studies showed high stability of the Cu chelate site (4,4-dimethyldithiosemicarbazone structure) and enzymatic hydrolysis of the ester site (ethylester or acetylester). The 62Cu-labeled compounds showed in vivo behavior which may be due to their ester hydrolysis.

Animals↗
PubMed1991

Characterization of technetium-99m complexes of pentane-2,4-dione bis(N-methylthiosemicarbazone).

Further characterization of the two neutral technetium-99m (99mTc) complexes of pentane-2,4-dione bis-(N-methylthiosemicarbazone) (PETS) was carried out using a new dianionic PETS derivative, 3,3-dimethyl-pentane-2,4-dione bis(N-methylthiosemicarbazone) (DM-PETS), and the well characterized 99mTc complex of 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (DADT) as references. While PETS generated two neutral 99mTc complexes, 99mTc-PETS-L1 and 99mTc-PETS-L2, by both the stannous reduction method and the ligand exchange reaction with six-coordinated 99mTc(V) complex of N,N'-ethylenebis(acetylacetone imine), DM-PETS formed only one neutral 99mTc complex. 99mTc-PETS-L2, the more lipophilic complex of the two 99mTc-PETS, was obtained with a much higher yield than 99mTc-PETS-L1 by the ligand exchange reaction of PETS with the five-coordinated 99mTc(V) complex of glucoheptonate. In addition, while 99mTc-PETS-L2 and 99mTc-DADT remained unchanged in the presence of CN- anions, a breakdown of the original complexes was observed in 99mTc-PETS-L1 and 99mTc-DM-PETS. All four 99mTc complexes exhibited similar brain, heart and pancreas extraction when injected into mice. These cumulative results imply that 99mTc-PETS-L1 and 99mTc-DM-PETS are six-coordinated mononuclear 99mTc(V) complexes and that 99mTc-PETS-L2 is a five-coordinated mononuclear 99mTc(V) complex. These results also suggest that while the chelate ring structure of the 99mTc-dithiosemicarbazone (DTS) chelate played a significant role in its stability, ionization of the third proton of the PETS molecule and the subsequent resonating structure afforded further stability to the 99mTc-PETS complex. Markedly high lipophilicity of the 99mTc-PETS-L2 may also be explained by assuming that 99mTc-PETS-L2 is the five-coordinated resonating structure.

Animals↗
PubMed1991

Diagnosis and treatment of left ventricular false aneurysm.

Three patients are presented in whom a false aneurysm of the left ventricle was surgically treated. False aneurysm of the left ventricle is an unusual consequence of ventricular wall rupture with containment of the resulting hematoma. Most false aneurysms of the left ventricle develop following myocardial infarction. The false aneurysm wall contains no myocardium. The false aneurysm has a great tendency to rupture, regardless of its size. One patient developed progressive congestive heart failure following a myocardial infarction. The other two patients were asymptomatic following myocardial infarction. Preoperative magnetic resonance imaging showed characteristics of a false aneurysm. These included a distinct discontinuance of the myocardium at the neck of the aneurysm and a narrow neck relative to the diameter of the aneurysm. Two patients underwent successful closure of the orifice of the false aneurysms. One patient underwent emergency surgery because of acute rupture while awaiting surgery but died of cerebral damage. Surgical correction of a false aneurysm is clearly advisable even in the absence of symptoms.

Echocardiography↗
PubMed1990

Ligandin binding phthalein complexone complex of technetium for hepatic function studies.

In our pursuit for liver functional diagnosis, development of bifunctional radiopharmaceutical containing iminodiacetic acid (IDA), as the technetium chelating site along with phthalein or fluorescein structure, the skeleton of BSP and Rose Bengal, long used for the assessment of liver function is considered. Among the various PC, PPC, TPC and calcein IDA derivatives commercially available, 99mTc-PC (PC: 3,3'-bis(N, N-dicarboxymethylaminomethyl)o-cresolphthalein) showed the highest hepatobiliary excretion. The functionality of the various technetium labeled phthalein and fluorescein IDA derivatives was evaluated by competitive BSP binding studies and by comparative binding with the hepatocyte specific protein, ligandin.

Animals↗
PubMed1990

62Cu-labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate for regional plasma volume measurement: application of new 62Zn/62Cu generator system.

62Cu-Labeling of human serum albumin-dithiosemicarbazone (HSA-DTS) conjugate was performed using a newly developed 62Zn/62Cu generator system. HSA-DTS was easily labeled with 62Cu, by simple mixing with 62Cu-generator eluate. In vivo blood clearance of 62Cu-HSA-DTS was similar to 131I-HSA, indicating the high applicability of 62Cu-HSA-DTS as a method for plasma volume measurement. In a positron emission tomography study of a dog, a clear plasma pool image of the head region was obtained.

Animals↗
PubMed1990

Stable and lipophilic technetium-99m dithiosemicarbazone complexes with 5-6-5 membered chelate ring structure.

Modification of the chelate ring structure of technetium-99m (99mTc) dithiosemicarbazone (DTS) chelate was carried out in pursuit of a more stable and lipophilic compound. A new DTS chelating molecule, pentane-2,4-dione bis(N-methylthiosemicarbazone) (PETS), with a 5-6-5 membered chelate ring structure, was synthesized and labeled with 99mTc, PETS generated two 99mTc compounds as major products. Both had much higher stability and lipophilicity than a 5-5-5 membered 99mTc DTS compound, as well as great stability in plasma. Both 99mTc-PETS compounds were rapidly extracted by the brain and heart when injected into mice. Thus, the modified chelate ring structure afforded a preferable characteristics to DTS chelate as for the chelating site for technetium radiopharmaceuticals.

Animals↗
PubMed1989

Design, synthesis and 64Cu labeling of fatty acid analogs containing dithiosemicarbazone chelate.

For the development of 62Cu labeled fatty acid analogs, two fatty acid analogs, containing dithiosemicarbazone (DTS) molecule as the 62Cu coordinating site, were designed and synthesized: a fatty acid analog containing DTS molecule at the omega-position, (a) the 12,13-dioxotetradecanoic acid di(N-methyl-thiosemicarbazone) (FA-DTS), and an omega-phenyl fatty acid analog containing DTS molecule at the para-position, (b) the p-carboxyundecylphenylglyoxal-di (N-methylthiosemicarbazone] (PFA-DTS). FA-DTS was synthesized by the reaction of ethyl diethoxyacetate with ethyl 11-bromonundecanate by successive decarboxylation and hydrolysis and final condensation with N-methylthiosemicarbazide. PFA-DTS was synthesized by the Friedel-Craft acylation of ethyl 11-phenylundecanate, selenium oxidation of the acetophenone derivative, followed by the condensation with N-methylthiosemicarbazide. Radiolabeling of FA-DTS and PFA-DTS with [64Cu]copper acetate was simple, rapid and quantitative. When injected into mice, both compounds were distributed and retained in the myocardium. These results offer a good basis for further development of 62Cu labeled fatty acid analogs.

Animals↗
PubMed1988

Immunoscintigraphy and pharmacokinetics of indium-111-labeled ZME-018 monoclonal antibody in patients with malignant melanoma.

Immunoscintigraphic and pharmacokinetic characteristics of 111In-labeled ZME-018 monoclonal antibody were examined in 8 patients with malignant melanoma. Each patient received a single intravenous infusion of 20 mg of ZME-018, coupled to 3 mCi of 111In without any acute toxicity. Scintigrams were taken 1, 3, and 6 days after the administration, and blood and urine samples were also taken frequently. Rapid clearance of some radioactivity was seen in early urine samples in the form of 111In DTPA, but after 1 day, urinary excretion of radioactivity was slow and steady, with an average of 2.5% of the injected dose excreted per day. The scans demonstrated that there was blood retention of radioactivity in the heart and great vessels 1 day after infusion and considerable clearance from the blood pool occurred by 3 days. However, 111In was deposited in the liver, spleen and bone for up to 6 days. The optimal time for imaging appeared to be at 3 days. Nineteen out of 26 known lesions or 6 out of 8 patients were positive. There were 21 lesions detected that were not suspected during the work-up the patient. Five patients developed human anti-mouse antibody in the serum by 3 weeks. These results suggest that immunoscintigraphy with 111In-labeled ZME-018 antibody is safe and useful for the detection of metastatic lesions in a selected group of patients with malignant melanoma.

Adult↗
PubMed1987

Preparation of 67Ga-labeled antibodies using deferoxamine as a bifunctional chelate. An improved method.

Radionuclides or anti-cancer drugs may be coupled to antibodies for specific transport to target tissues. We have previously reported that several proteins could be rapidly and efficiently labeled with gallium (67Ga) by using deferoxamine (DFO) as a bifunctional chelating agent. In the present paper, we have described the use of hetero-bifunctional agents for the conjugation of DFO with antibodies and investigated the effect of coupling agents on in vitro properties and biodistribution of 67Ga-labeled antibodies. 67Ga-labeled monoclonal antibodies retained antigen-binding activity when prepared under optimum conditions. The use of hetero-bifunctional reagents, such as succinimidyl 6-maleimido-hexanoate (EMCS) or N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), which link thioether bonds and disulfide bridges prevented the formation of polymerized antibodies. Although high non-specific uptake in the liver was observed with radiolabels prepared by the homo-bifunctional agent glutaraldehyde, uptake in the liver was low with conjugates linked by hetero-bifunctional agents. 67Ga-labeled antibodies with thioether bonds showed in vivo stability, but the clearance from the circulation was the fastest with the radiolabel holding disulfide bonds. The coupling reagents used to link DFO and antibodies greatly influenced both in vitro properties and in vivo distribution of labeled antibodies and 67Ga-labeled antibodies provide a good model for the study of coupling methods and biodistribution of antibody conjugates.

Animals↗
PubMed1987

Procurement of radioiodinated glucose derivative and its biological character.

Radiolabeled glucose derivatives are attracting great interest in the clinical field. Development of an analogous substrate labeled with a practical radionuclide, 123I, is most desirable, however, no radioiodine labeled glucose derivative has been reported as being chemically and biologically compatible. Thus, in the present study, a glucose derivative substituted at the C-2 position by a p-iodobenzyl group, a 2-O-(p-iodobenzyl)-D-glucose (IBG) was designed and its synthesis was carried out. A very easy and simple synthetic method was developed, and the obtained IBG showed appropriate purity and stability for its radioiodination. [125I]IBG was obtained by radioisotopic exchange reaction with high radiochemical purity and radiochemical yield, requiring no purification. The good in vivo and in vitro stability and the chemical and biological characteristic displayed by the new [125I]IBG stimulated the measurement of the brain uptake index (BUI). In the presence of glucose, brain uptake inhibition was detected, a good indication of a glucose carrier mediator for the transport of [125I]IBG through the blood-brain barrier, a similar feature to that of [14C]glucose or 3-O-[14C]methylglucose. The newly designed ligand IBG holds good promise for the study of regional cerebral glucose utilization, should the 123I become available.

Animals↗
PubMed1987

Preparation and properties of antitumor monoclonal antibodies labeled with metallic radionuclides indium-111, gallium-67, and technetium-99m.

In this study, metallic radionuclides such as 111In, 67Ga, or 99mTc produced clear visualization in scintigraphic imaging of tumors; they have short half-lives and can easily be used in the radiolabeling of monoclonal antibodies by using bifunctional chelating agents. Under selected conditions, these radiolabeled antibodies were stable both in vitro and in vivo with no loss of the antigen-binding activity. Despite high background imaging of the liver and kidney, transplanted tumors in nude mice were clearly visualized with 111In-, 67Ga-, and 99mTc-labeled antibodies at 6, 24, or 48 hours after the injection. Although tissue distribution in the liver, kidney, and bone was different among radionuclides used for the labeling, all tumor to blood ratios were higher than those of radioiodinated monoclonal antibodies. These results provide a good basis for studies of the clinical usefulness of 111In-, 67Ga-, and 99mTc-labeled monoclonal antibodies for radioimmunoimaging.

Animals↗
PubMed1987

Technetium-99m-labeled monoclonal antibody with preserved immunoreactivity and high in vivo stability.

Recent availability of monoclonal antibodies (MoAb) and their radiolabeling through the use of the bifunctional chelating agents (BCA) have become an alternative procedure for in vivo radioimmunodetection. Using a newly synthesized BCA, a p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), the coupling and technetium-99m (99mTc) labeling of monoclonal IgG against hCG were carried out. In the system presented, factors affecting stability and immunoreactivity were examined. Immunoreactivity of the original IgG (56C) was preserved by conjugating one CE-DTS molecule per molecule of IgG (56C) using the phosphorylazide method, however, 99mTc labeling pH affected the immunoreactivity and limited the 99mTc labeling reaction between pH 4.5 and 6.2. A screening of labeling conditions, such as pH, reaction time, and reducing agent system were then carried out. Technetium-99m-labeled IgG (56C), [99mTc]CE-DTS-IgG (56C), showed good stability upon incubation with mice sera and comparable mice biodistribution to that of indium-111 (111In) DTPA-IgG (56C). Thus, these results indicate the excellent potential of CE-DTS as a BCA for labeling MoAb with 99mTc.

Animals↗
PubMed1986

In the procurement of stable 99mTc labeled protein using bifunctional chelating agent.

Recently, technetium-99m (99mTc) labeling of proteins through the use of a bifunctional chelating agent (BCA) has been reported. In previous work, a BCA containing a di(N-methylthiosemicarbazone) (DTS) moiety for 99mTc has offered good potential; however, conjugation with bulky proteins has induced some steric interference in the 99mTc labeling step using the stannous chloride method. In order to minimize this effect, changes in the hydrocarbon chain length (spacer) between the DTS and the protein binding site (carboxyl group), as well as the chemical state of the reducing agent, stannous chloride, were considered of interest. DTS molecules with variable spacer length (n = 0, 2, 4) were synthesized, coupled with human serum albumin and labeled with 99mTc. Also, stannous chloride prepared in different media was evaluated. Validity of the present approach is tested and discussed.

Animals↗
PubMed1986

Search for 99mTc labeled DTS bifunctional radiopharmaceutical: role of functional groups in myocardial accumulation.

Development of 99mTc-bifunctional radiopharmaceutical (BR) is attracting the interest of various research groups. In the present paper, various molecules containing a neutral 99mTc-dithiosemicarbazone (DTS) structure as the technetium chelating site, along with various functional groups (amino, carboxyl or isobutyl group with diverse charge) are tested for their chemical or biological functions. The study on the effect of those functional groups is carried out in vitro and in vivo. The validity of introducing an amino group along with the technetium chelating site DTS for myocardial accumulation is discussed.

Animals↗
PubMed1986

Design of bifunctional radiopharmaceutical for the development of 99mTc complexes for myocardial imaging agents.

Several bifunctional radiopharmaceuticals (BR), molecules containing a neutral 99mTc-dithiosemicarbazone (DTS) structure as a chelating site, along with a functional amino group (primary tertiary and quaternary amino group) are tested for their chemical or biological functionalities as myocardial agents. Investigation of these amino compounds is carried out in vitro and in vivo. Mice (ddY) distribution studies show a high radioactivity distribution in heart with every tested derivative, but the highest heart to blood ratio of 2.92 (1 h) is achieved with the quaternary amino DTS. Also, this derivative displays low lung uptake inducing a proper target/non-target ratio for myocardial agent. The role conveyed by the various amino containing side chain in the biodistribution and validity of DTS derivative as BR are discussed.

Animals↗
PubMed1986

Synthesis and evaluation of a new bifunctional chelating agent for 99mTc labeling proteins: p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone).

A new bifunctional chelating agent, p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), containing a di(N-methylthiosemicarbazone) as the technetium coordinating site and an aralkyl carboxylate site for the protein conjugation was synthesized. Coupling to human serum albumin (HSA), selected as a model protein was carried out by the phosphorylazide method using diphenylphosphoryl azide (DPPA). The conjugation level of CE-DTS to HSA played a critical role in its biological evaluation. A 99mTc-CE-DTS-HSA with high in vivo stability was obtained when CE-DTS was coupled to HSA at 1:1 molar ratio. This compound showed similar in vivo stability to 131I labeled HSA in mice and rabbits.

Animals↗
PubMed1986

In the procurement of a neutral and compact monomeric complex of dithiosemicarbazone (DTS) derivative: 99mTc-KTS.

As a basic structure of a bifunctional radiopharmaceutical (BR), dithiosemicarbazone (DTS) enables the formation of a small conjugated chelating ring with divalent metals (Cu2+, Zn2+, Ni2+), yielding stable and compact complexes. In the development of a neutral and compact monomeric DTS complex of technetium (99mTc), a DTS containing ligand, kethoxal-bis(thiosemicarbazone) (KTS) was selected. A well known monomeric Cu-KTS complex (or 64Cu-KTS) is taken as a model compound, and in vitro (TLC, EP, HPLC) and in vivo (mice biodistribution) studies were compared. Using the stannous chloride method, under conditions to avoid the hydrolytic polynucleation of technetium, a good yield of 99mTc-KTS with characteristics resembling the non-charged, compact and stable Cu-KTS is obtained, in in vitro as well as in vivo studies. The importance of DTS as the constituent of a BR is discussed.

Animals↗