Quantum Sensors To Track Total Redox-Status and Oxidative Stress in Cells and Tissues Using Electron-Paramagnetic Resonance, Magnetic Resonance Imaging, and Optical Imaging.

Total redox capacity (TRC) and oxidative stress (OxiStress) of biological objects (such as cells, tissues, and body fluids) are some of the most frequently analyzed parameters in life science. Development of highly sensitive molecular probes and analytical methods for detection of these parameters is a rapidly growing sector of BioTech's R&D industry. The aim of the present study was to develop quantum sensors for tracking the TRC and/or OxiStress in living biological objects using electron-paramagnetic resonance (EPR), magnetic resonance imaging (MRI), and optical imaging.

Single-Dose Cisplatin Pre-Treatment Enhances Efficacy of ROBO1-Targeted Radioimmunotherapy.

We previously reported that radioimmunotherapy (RIT) using Y-labeled anti-ROBO1 IgG (Y-B5209B) achieved significant anti-tumor effects against small-cell lung cancer (SCLC) xenografts. However, subsequent tumor regrowth suggested the necessity for more effective therapy. Here, we evaluated the efficacy of combination Y-B5209B and cisplatin therapy in NCI-H69 SCLC xenograft mice.

Adnexal masses characterized on 3 tesla magnetic resonance imaging - added value of diffusion techniques.

Background To assess different types of adnexal masses as identified by 3T MRI and to discuss the added value of diffusion techniques compared with conventional sequences. Patients and methods 174 women age between 13 and 87 underwent an MRI examination of the pelvis for a period of three years. Patients were examined in two radiology departments - 135 of them on 3 Tesla MRI Siemens Verio and 39 on 3 Tesla MRI Philips Ingenia.

64Cu-labeled minibody D2101 visualizes CDH17-positive gastric cancer xenografts with short waiting time.

Objective: We previously reported In-labeled anti-cadherin17 (CDH17) IgG visualized CDH17-positive gastric cancer xenografts. Unfortunately, a long waiting time was required to obtain high-contrast images due to long blood retention (blood half-life: 26 h). To accelerate blood clearance, we have developed anti-CDH17 minibody (D2101 minibody) and evaluated the pharmacokinetics in gastric cancer mouse models.

Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression.

Background: CD73 is an ectonucleotidase regulating extracellular adenosine concentration and plays an important role in adenosine-mediated immunosuppressive pathways. The efficacy of CD73-targeted therapy depends on the expression levels of CD73; therefore, monitoring CD73 status in cancer patients would provide helpful information for selection of patients who would benefit from CD73-targeted therapy. Here, we evaluated the ability of In-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe.

In-labeled anti-cadherin17 antibody D2101 has potential as a noninvasive imaging probe for diagnosing gastric cancer and lymph-node metastasis.

Objective: Cadherin-17 (CDH17) is a transmembrane protein that mediates cell-cell adhesion and is frequently expressed in adenocarcinomas, including gastric cancer. CDH17 may be an effective diagnostic marker for the staging of gastric cancer. Here, we developed an In-labeled anti-CDH17 monoclonal antibody (Mab) as an imaging tracer and performed biodistribution and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies using mice with CDH17-positive gastric cancer xenografts.

Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic Agent At-MABG for the Treatment of Malignant Pheochromocytoma in Normal Mice.

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.

Anti‑tissue factor antibody‑mediated immuno‑SPECT imaging of tissue factor expression in mouse models of pancreatic cancer.

Tissue factor (TF) has emerged as a critical factor in oncogenic events, leading to the development of TF‑targeted diagnostic and therapeutic approaches. A non‑invasive imaging method to evaluate target molecule expression with high sensitivity and high quantitative ability is imperative for selecting the appropriate patients for TF‑targeted therapy. To elucidate the potential of 111In‑labeled anti‑TF antibody 1849 (111In‑1849) as an immuno‑single photon emission computed tomography (SPECT) probe targeting TF, we evaluated TF‑dependent in vitro binding as well as in vivo biodistribution and tumor accumulation of 111In‑1849 in pancreatic cancer cells/models with varying TF expression levels.

Therapeutic efficacy evaluation of radioimmunotherapy with Y-labeled anti-podoplanin antibody NZ-12 for mesothelioma.

Podoplanin is a type I transmembrane sialomucin-like glycoprotein that is highly expressed in malignant mesothelioma. The rat-human chimeric antibody NZ-12 has high affinity for human podoplanin and antibody-dependent cellular cytotoxicity and is applicable for radioimmunotherapy (RIT) to enhance the antitumor effect. In the present study, we evaluated the in vivo and in vitro properties of radiolabeled NZ-12 and the antitumor effect of RIT with Y-labeled NZ-12 in an NCI-H226 (H226) malignant mesothelioma xenograft mouse model.

Near-infrared photoimmunotherapy of pancreatic cancer using an indocyanine green-labeled anti-tissue factor antibody.

Aim: To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor (TF) antibody conjugated to indocyanine green (ICG) in a pancreatic cancer model.

Methods: Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG anti-TF monoclonal antibody 1849 (anti-TF 1849) to a NIR photosensitizer, ICG.

Direct comparison of 2‑amino[3‑11C]isobutyric acid and 2‑amino[11C]methyl‑isobutyric acid uptake in eight lung cancer xenograft models.

The non‑natural amino acid positron emission tomography tracers, 2‑amino[3‑11C]isobutyric acid ([3‑11C]AIB) and 2‑amino[11C]methyl‑isobutyric acid ([11C]MeAIB), are metabolically stable in vivo and accumulate in tumors. [3‑11C]AIB is transported into cells mainly via the amino acid transport system A and partially via systems L and ASC, whereas [11C]MeAIB is transported into cells specifically via system A. How transport via the different systems affects the tumor uptake of these tracers, however, is unclear.

Efficacy Evaluation of Combination Treatment Using Gemcitabine and Radioimmunotherapy with Y-Labeled Fully Human Anti-CD147 Monoclonal Antibody 059-053 in a BxPC-3 Xenograft Mouse Model of Refractory Pancreatic Cancer.

The poor prognosis of pancreatic cancer requires the development of more effective therapy. CD147 expresses in pancreatic cancer with high incidence and has a crucial role in invasion and metastasis. We developed a fully human monoclonal antibody (059-053) with high affinity for CD147.

Combined treatment of pancreatic cancer xenograft with Y-ITGA6B4-mediated radioimmunotherapy and PI3K/mTOR inhibitor.

Aim: To investigate the therapeutic effect of combined integrin αβ-targeted radioimmunotherapy (RIT) and PI3K/mTOR inhibitor BEZ235 in a pancreatic cancer model.

Methods: Phosphorylation of Akt, mTOR, the downstream effectors eukaryotic initiation factor 4E binding protein 1 (4EBP1) and S6 ribosomal protein (S6) were evaluated in BxPC-3 human pancreatic cancer cells treated with Yttrium-90 (Y) labeled anti-integrin αβ antibody (ITGA6B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay.

Synthesis and evaluation of C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression.

Upregulated monocarboxylate transporters (MCTs) in tumors are considered diagnostic imaging targets. Herein, we synthesized the positron emission tomography probe candidates coumarin analogs 2 and 3, and showed 55 times higher affinity of 2 for MCTs than a representative MCT inhibitor. Whereas [C]2 showed low tumor accumulation, probably due to adduct formation with plasma proteins, [C]2 showed high initial brain uptake, suggesting that the scaffold of 2 has properties that are preferable in imaging probes for the astrocyte-neuron lactate shuttle.