Publications by authors named "Noriko S Ishioka"

Intracellular ATP is released outside cells by various stimuli and is involved in cytoprotection by activating purinergic receptors. However, it remains unclear whether targeted radionuclide therapy induces extracellular ATP release. Here, we prepared I-labeled trastuzumab (I-trastuzumab) and examined extracellular ATP release and its roles in I-trastuzumab's growth inhibitory effects.

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Radiohalogens with a short half-life are useful radioisotopes for radiotheranostics. Astatine-211 is an α-emitting radiohalogen and is expected to be applicable to targeted α therapy. A neopentyl labeling group is an effective hydrophilic labeling unit for various radiohalogens, which includes At.

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Radioactive isotope (RI) metals are a new type of tracer for positron emission tomography generated from the target metal by proton irradiation using a cyclotron. The generated metal RIs need to be separated from the target metal rapidly and effectively. In the present study, we developed a 3D-printed flow device to separate metal RIs from target metals.

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Article Synopsis
  • - The study compares the effectiveness of Y (Yttrium) and Lu (Lutetium) as β-emitters in radionuclide therapy using tumor-bearing mice with different tumor growth rates.
  • - Results showed that while Y-Ab had a superior therapeutic effect in fast-growing tumors, Lu-Ab exhibited longer efficacy in slow-growing tumors due to its longer half-life.
  • - The findings suggest that the choice between using Y or Lu for therapy should be based on the growth rate of the specific cancer to achieve optimal treatment outcomes.
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Introduction: Meta-[At]astato-benzylguanidine ([At]MABG) accumulates in pheochromocytoma via norepinephrine transporter (NET) and leads to a strong antitumor effect, but it also distributed in normal tissues non-specifically. Meta-[I]iodo-benzylguanidine ([I]MIBG), an iodine-labeled analog of [At]MABG, is known to be transported by not only NET but also organic cation transporter (OCT). The involvement of OCT in [At]MABG uptake is still largely unknown.

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Prostate-specific membrane antigen (PSMA), expressed in prostate cancer cells, is being investigated extensively worldwide as a target for imaging and therapy of prostate cancer. Various radioiodinated PSMA imaging probes have been developed, and their structure has a peptidomimetic urea-based skeleton as a pharmacophore. For direct radioiodination of molecules containing these peptidomimetic structures, prior studies performed radioiododestannylation or electrophilic radioiodination of tyrosine residues.

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Preparing compounds containing the radioisotope Cu for use in positron emission tomography cancer diagnostics is an ongoing area of research. In this study, a highly efficient separation method to recover Cu generated by irradiating the target Ni with a proton beam was developed by employing a flow electrolysis cell (FE). This system consists of (1) applying a reduction potential for the selective adsorption of Cu from the target solution when dissolved in HCl and (2) recovering the Cu deposited onto the carbon working electrode by desorbing it from the FE during elution with 10 mmol/L HNO, which applies an oxidation potential.

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Short-lived radioactive metals are important tracers in clinical diagnosis. Radioactive metals for clinical use are produced from suitable target metals in cyclotrons. The trace amount of radioactive metal produced is contained in a relatively large amount of target metal.

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Article Synopsis
  • Researchers developed a new method called RAP (RAtio of Pharmacokinetics) for converting absorbed doses of At-meta-astatobenzylguanidine (At-MABG) using a single measurement of biodistribution.
  • The study focused on mathematically refining the RAP method to determine the best timing for this measurement, using a one-compartment model for biological clearance.
  • Results indicated that the refined RAP method was accurate, predicting absorbed doses within 10% error, and identified 4 hours post-injection as the optimal timing for measurement.
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L-type amino acid transporter 1 (LAT1) might be a useful target for tumor therapy since it is highly expressed in various types of cancers. We previously developed an astatine-211 (At)-labeled amino acid derivative, 2-At-astato-α-methyl-L-phenylalanine (2-At-AAMP), and demonstrated its therapeutic potential for LAT1-positive cancers. However, the therapeutic effect of 2-At-AAMP was insufficient, probably due to its low tumor retention.

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The high stability of 2,2-dihydroxymethyl-3-[F]fluoropropyl-2-nitroimidazole ([F]DiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all I-labeled compounds remained stable against nucleophilic substitution, only a I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against deiodination.

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(1) Background: Deferoxamine B (DFO) is the most widely used chelator for labeling of zirconium-89 (Zr) to monoclonal antibody (mAb). Despite the remarkable developments of the clinical Zr-immuno-PET, chemical species and stability constants of the Zr-DFO complexes remain controversial. The aim of this study was to re-evaluate their stability constants by identifying species of Zr-DFO complexes and demonstrate that the stability constants can estimate radiochemical yield (RCY) and chelator-to-antibody ratio (CAR).

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Article Synopsis
  • *Methods*: Researchers created 3200 virtual datasets using the Monte Carlo method and analyzed dose calculations through a new RAP method, which improves upon traditional methods by employing pharmacokinetic data.
  • *Results*: The RAP method successfully predicted At-MABG doses similar to I-MIBG doses, proving effective across different cell lines, though it struggled with long-term prediction from short-term data.
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Radioactive metals are applied in biochemistry, medical diagnosis such as positron emission tomography (PET), and cancer therapy. However, the activity of radioisotopes exponentially decreases with time; therefore, rapid and reliable probe preparation methods are strongly recommended. In the present study, electrodialytic radioactive metal ion handling is studied for counter ion conversion and in-line probe synthesis.

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Introduction: Targeted α-radionuclide therapy has attracted attention as a promising therapy for refractory cancers. However, the application is limited to certain types of cancer. Since L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers, we prepared an LAT1-selective α-radionuclide-labeled amino acid analog, 2-[At]astato-α-methyl-L-phenylalanine (2-[At]AAMP), and evaluated its potential as a therapeutic agent.

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Article Synopsis
  • Overexpression of the epidermal growth factor receptor (EGFR) is a key target for treating non-small cell lung cancer (NSCLC), but the effectiveness of cetuximab, an EGFR-targeting drug, remains uncertain due to difficulties in identifying appropriate patients.
  • This study explored the use of radiolabeled cetuximab as a non-invasive method to predict the drug's accumulation in NSCLC tumors with varying EGFR levels using PET imaging in mouse models.
  • Results indicated that higher EGFR expression significantly correlated with increased cetuximab uptake, suggesting that immuno-PET imaging could be a useful clinical tool for anticipating which NSCLC patients would benefit from cetuximab treatment.
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Positron emission tomography (PET) imaging with F-labeled α-methyl-substituted amino acids exerts significant influence on differential diagnosis of malignant tumors and tumor-like lesions. Exclusive uptake via L-type amino acid transporter 1 (LAT1), a tumor-specific transporter, accounts for their excellent tumor specificity and low background accumulation. However, further refinement and optimization in their tumor accumulation and pharmacokinetics are sorely needed.

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The α-emitter At-labeled meta-astatobenzylguanidine (At-MABG) has a strong antitumor effect on pheochromocytoma xenograft tumors and holds great promise as a new therapeutic option for malignant pheochromocytoma. To evaluate the acute radiation-related toxicity of At-MABG, we conducted biodistribution and dosimetry studies of At-MABG in ICR mice to estimate the doses absorbed by organs. We determined the maximum tolerated doses (MTD) of At-MABG on the basis of body weight loss and assessed the acute radiation-related toxicity induced by MTD administration on the basis of organ weights, histologic features, hematologic indices, and biochemical indices.

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Targeted α-particle therapy is a promising option for patients with malignant pheochromocytoma. Recent observations regarding -At-astato-benzylguanidine (At-MABG) in a pheochromocytoma mouse model showed a strong anti-tumor effect, though the molecular mechanism remains elusive. Here, we present the first comprehensive RNA-sequencing (RNA-seq) data for pheochromocytoma cells based on At-MABG administration experiments.

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The 211At-labeled compound, 4-[211At]astato-l-phenylalanine, is one of the most promising amino acid derivatives for use in targeted alpha therapy (TAT) for various cancers. Electrophilic demetallation of a stannyl precursor is the most widely used approach for labeling biomolecules with 211At. However, the low acid-resistance of the stannyl precursor necessitates the use of an N- and C-terminus-protected precursor, which results in a low overall radiochemical yield (RCY) due to the multiple synthetic steps involved.

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Astatine-211 is a promising radionuclide for targeted radiotherapy. It is required to image the distribution of targeted radiotherapeutic agents in a patient's body for optimization of treatment strategies. We proposed to image At with high-energy photons to overcome some problems in conventional planar or single-photon emission computed tomography imaging.

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Purpose: Therapeutic options for patients with malignant pheochromocytoma are currently limited, and therefore new treatment approaches are being sought. Targeted radionuclide therapy provides tumor-specific systemic treatments. The β-emitting radiopharmaceutical meta-I-iodo-benzylguanidine (I-MIBG) provides limited survival benefits and has adverse effects.

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Objective: Radionuclide therapy with low-energy auger electron emitters may provide high antitumor efficacy while keeping the toxicity to normal organs low. Here we evaluated the usefulness of an auger electron emitter and compared it with that of a beta emitter for tumor treatment in in vitro models and conducted a dosimetry simulation using radioiodine-labeled metaiodobenzylguanidine (MIBG) as a model compound.

Methods: We evaluated the cellular uptake of I-MIBG and the therapeutic effects of I- and I-MIBG in 2D and 3D PC-12 cell culture models.

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System l amino acid transporter 1 (LAT1) is highly expressed in various types of human cancer, and contributes to cancer growth and survival. Recently, we have shown that LAT1 expression is closely related to the growth and aggressiveness of esophageal cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal cancer growth.

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Selective separation and sensitive detection of dissolved silicon and boron (DSi and DB) in aqueous solution was achieved by combining an electrodialytic ion isolation device (EID) as a salt remover, an ion-exclusion chromatography (IEC) column, and a corona charged aerosol detector (CCAD) in sequence. DSi and DB were separated by IEC on the H(+)-form of a cation exchange resin column using pure water eluent. DSi and DB were detected after IEC separation by the CCAD with much greater sensitivity than by conductimetric detection.

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