scholarly journals Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 918
Author(s):  
Marco Verona ◽  
Sara Rubagotti ◽  
Stefania Croci ◽  
Sophia Sarpaki ◽  
Francesca Borgna ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Single Photon ◽  
Photon Emission ◽  
Tumor Cell Line ◽  
Normal Tissues ◽  
Molar Activity ◽  
Suitable Target ◽  
Indium 111 ◽  
Preliminary Study

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [111In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.

Development of radiolabeled mapatumumab and imaging in solid tumor patients who are treated with gemcitabine, cisplatin, and mapatumumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14521-e14521 ◽  
Author(s):  
C. Oldenhuis ◽  
E. C. Dijkers ◽  
E. W. Duiker ◽  
N. L. Fox ◽  
J. L. Klein ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Radiochemical Purity ◽  
Single Photon ◽  
Phase 1 ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Multiple Time ◽  
Tracer Injection ◽  
Camera Imaging

e14521 Background: Mapatumumab is a fully human agonistic monoclonal antibody (mAb) to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1). Mapatumumab combined with gemcitabine and cisplatin increased cytotoxicity in preclinical models and was safe in a phase 1 study. To study its biodistribution, 111Indium (111In) labeled mapatumumab was developed for γ-camera imaging and tested in mice. Subsequently, 111In-mapatumumab scintigraphy was performed in patients (pts). Methods: Mapatumumab was labeled with 111In. Labeling efficiency, radiochemical purity, stability and binding properties were determined in vitro. Biodistribution was studied at multiple time points in nude mice bearing human xenografts (SKBR3 or SW948). Tissue activity was expressed as % injected dose/gram tissue (%ID/g). In a feasibility study, gemcitabine 1250 mg/m2 IV on days 1 and 8, cisplatin 80 mg/m2 IV and mapatumumab 20 mg/kg on day 1 was administered to advanced solid tumor pts every 21 days. In cycles 1 and 3, pts underwent γ-camera imaging directly, and at day 1, 3, and 6 after 150 MBq 111In-mapatumumab IV (planar and single-photon emission computed tomography (SPECT)). Results: Labeling efficiency was 92.0% and radiochemical purity 96.0%. 111In-mapatumumab was stable in serum for 1 week at 37°C and specific TRAIL-R1 binding was maintained after labeling. In mice, high uptake was seen in liver (8.14 ± 0.75 %ID/g), kidneys (16.30 ± 1.75 %ID/g), spleen (7.25 ± 2.64 %ID/g) and bone (5.68 ± 1.31 %ID/g), with a maximum 24–72 hours (h) after tracer injection. Maximum uptake in the xenografts was observed after 72 h (7.55 ± 3.54 %ID/g for SKBR3 and 6.21 ± 2.03 %ID/g for SW948). Five pts have been enrolled in the ongoing clinical study. Known tumor lesions (by CT-scan) showed variable tracer uptake in 3 pts, while within pts not all known tumor lesions were positive on SPECT. Conclusions: Mapatumumab can be efficiently radiolabeled for clinical use. Preliminary results show that mapatumumab scintigraphy identifies some but not all tumor lesions in pts. This is the first demonstration that mAb targeting a TRAIL-R distributes to tumor tissues in patients and could potentially guide mapatumumab therapy. [Table: see text]

CITOTOXICITY OF INDIUM-111-LABELED AUTOLOGOUS WBC

2019 ◽  
pp. 18-22
Author(s):  
K. A. Luneva ◽  
K. E. Ternovskaya ◽  
O. E. Klement’eva ◽  
A. S. Lunev
Keyword(s):  
Cytotoxic Effect ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Blood Leukocytes ◽  
Cytotoxic Effects ◽  
Indium 111 ◽  
Single Photon Emission Computed ◽  
Photon Emission Computed Tomography ◽  
Subsequent Introduction

The radiopharmaceutical precursor «Oxind, 111In» is a complex compound for labeling autologous leukocytes of human blood and their subsequent introduction for non-specific visualization and localization of inflammation foci of different nature by single-photon emission computed tomography (SPECT). The cytotoxic effect of lyophilisate for preparation of radiopharmaceutical preparation «Oxind, 111In» and its radiopharmaceutical precursor on rabbit blood leukocytes has been investigated. In the course of studies of the cytotoxicity of the lyophilisate for the preparation of a radiopharmaceutical precursor with successively increasing concentrations of the main substance, 8-hydroxyquinoline, the permissible concentrations have been determined and the absolutely cytotoxic concentration was achieved.In the study of the cytotoxic effect of the precursor of radiopharmaceutical on two dosages that differ by 10 times in volume activities (MBq / ml), the absence of cytotoxic effects has been confirmed.

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

SPECT Quantification of [123I]Iomazenil Binding to Benzodiazepine Receptors in Nonhuman Primates: II. Equilibrium Analysis of Constant Infusion Experiments and Correlation with in vitro Parameters

1994 ◽  
Vol 14 (3) ◽  
pp. 453-465 ◽  
Author(s):  
Marc Laruelle ◽  
Anissa Abi-Dargham ◽  
Mohammed S. AI-Tikriti ◽  
Ronald M. Baldwin ◽  
Yolanda Zea-Ponce ◽  
...  
Keyword(s):  
Specific Activity ◽  
Single Photon ◽  
Benzodiazepine Receptors ◽  
Photon Emission ◽  
Benzodiazepine Receptor ◽  
Equilibrium Analysis ◽  
Constant Infusion ◽  
Scatchard Analysis

In vivo benzodiazepine receptor equilibrium dissociation constant, KD, and maximum number of binding sites, Bmax, were measured by single photon emission computerized tomography (SPECT) in three baboons. Animals were injected with a bolus followed by a constant i.v. infusion of the high affinity benzodiazepine ligand [123I]iomazenil. Plasma steady-state concentration and receptor–ligand equilibrium were reached within 2 and 3 h, respectively, and were sustained for the duration (4–9 h) of the experiments (n = 15). At the end of the experiments, a receptor saturating dose of flumazenil (0.2 mg/kg) was injected to measure nondisplaceable activity. Experiments were carried out at various levels of specific activity, and Scatchard analysis was performed for derivation of the KD (0.59 ± 0.09 n M) and Bmax (from 126 n M in the occipital region to 68 n M in the striatum). Two animals were killed and [125I]iomazenil Bmax and KD were measured at 22 and 37°C on occipital homogenate membranes. In vitro values of Bmax (114 ± 33 n M) and 37°C KD (0.66 ± 0.16 n M) were in good agreement with in vivo values measured by SPECT. This study demonstrates that SPECT can be used to quantify central neuroreceptors density and affinity.

scholarly journals Introduction to Infrared and Raman-Based Biomedical Molecular Imaging and Comparison with Other Modalities

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5547
Author(s):  
Carlos F. G. C. Geraldes
Keyword(s):  
Computed Tomography ◽  
Molecular Imaging ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Raman Imaging ◽  
Emission Computed Tomography ◽  
Label Free ◽  
Advantages And Disadvantages

Molecular imaging has rapidly developed to answer the need of image contrast in medical diagnostic imaging to go beyond morphological information to include functional differences in imaged tissues at the cellular and molecular levels. Vibrational (infrared (IR) and Raman) imaging has rapidly emerged among the molecular imaging modalities available, due to its label-free combination of high spatial resolution with chemical specificity. This article presents the physical basis of vibrational spectroscopy and imaging, followed by illustration of their preclinical in vitro applications in body fluids and cells, ex vivo tissues and in vivo small animals and ending with a brief discussion of their clinical translation. After comparing the advantages and disadvantages of IR/Raman imaging with the other main modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography/single-photon emission-computed tomography (PET/SPECT), ultrasound (US) and photoacoustic imaging (PAI), the design of multimodal probes combining vibrational imaging with other modalities is discussed, illustrated by some preclinical proof-of-concept examples.

scholarly journals Room-temperature single-photon emission from zinc oxide nanoparticle defects and their in vitro photostable intrinsic fluorescence

Nanophotonics ◽  
2017 ◽  
Vol 6 (1) ◽  
pp. 269-278 ◽  
Author(s):  
Kelvin Chung ◽  
Timothy J. Karle ◽  
Asma Khalid ◽  
Amanda N. Abraham ◽  
Ravi Shukla ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Room Temperature ◽  
Single Photon ◽  
Photon Emission ◽  
Intrinsic Defect ◽  
Single Photon Emission ◽  
Silica Substrate ◽  
Skin Cells ◽  
Oxide Nanoparticle

AbstractZinc oxide (ZnO) is a promising semiconductor that is suitable for bioimaging applications due to its intrinsic defect fluorescence. However, ZnO generally suffers from poor photostability. We report room-temperature single-photon emission from optical defects found in ZnO nanoparticles (NPs) formed by ion implantation followed by thermal oxidation in a silica substrate. We conduct a thorough investigation into the photophysics of a particularly bright defect and identify other single emitters within the NPs. Photostability was observed when the NPs were removed from the growth substrate and taken up by skin cells for in vitro imaging.

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