Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents

To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.

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Design, Preparation, and Evaluation of a Novel 99mTcN Complex of Ciprofloxacin Xanthate as a Potential Bacterial Infection Imaging Agent

Molecules ◽

10.3390/molecules25245837 ◽

2020 ◽

Vol 25 (24) ◽

pp. 5837

Author(s):

Si’an Fang ◽

Yuhao Jiang ◽

Qianqian Gan ◽

Qing Ruan ◽

Di Xiao ◽

...

Keyword(s):

Bacterial Infection ◽

Radiochemical Purity ◽

Binding Assay ◽

Sterile Inflammation ◽

Good Stability ◽

Imaging Agent ◽

Imaging Agents ◽

Infection Imaging ◽

Preparation And Evaluation

In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [99mTcN]2+ core to obtain the 99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that 99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that 99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to 99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of 99mTcN-CPF2XT were higher and the uptakes of 99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that 99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

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High non-specific binding of the β1-selective radioligand 2-125I-ICI-H

Nuklearmedizin ◽

10.1055/s-0038-1625187 ◽

2003 ◽

Vol 42 (04) ◽

pp. 173-180 ◽

Cited By ~ 6

Author(s):

M. P. Law ◽

K. Kopka ◽

St. Wagner ◽

S. Luthra ◽

V. W. Pike ◽

...

Keyword(s):

Specific Activity ◽

Single Photon ◽

Specific Binding ◽

Photon Emission ◽

Radiochemical Yield ◽

Emission Computed Tomography ◽

Biodistribution Studies ◽

Positron Emission

Summary: Aim: As results of cardiac biopsies suggest, myocardial β1-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess β-adrenoceptors non-invasively. Among the novel racemic analogues of the established β1-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β1-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac β-adrenoceptors. The radiolabelled counterpart 2-125I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac β1-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125I-ICI-H is no suitable radiotracer for imaging in vivo.

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

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190304120011 ◽

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.

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

Molecules ◽

10.3390/molecules25235547 ◽

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.

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Ocular Biodistribution Studies Using Molecular Imaging

Pharmaceutics ◽

10.3390/pharmaceutics11050237 ◽

2019 ◽

Vol 11 (5) ◽

pp. 237 ◽

Cited By ~ 3

Author(s):

Ana Castro-Balado ◽

Cristina Mondelo-García ◽

Miguel González-Barcia ◽

Irene Zarra-Ferro ◽

Francisco J Otero-Espinar ◽

...

Keyword(s):

Molecular Imaging ◽

Single Photon ◽

Imaging Techniques ◽

Photon Emission ◽

High Sensitivity ◽

New Drugs ◽

Emission Computed Tomography ◽

Pharmacokinetic Data ◽

Biodistribution Studies

Classical methodologies used in ocular pharmacokinetics studies have difficulties to obtain information about topical and intraocular distribution and clearance of drugs and formulations. This is associated with multiple factors related to ophthalmic physiology, as well as the complexity and invasiveness intrinsic to the sampling. Molecular imaging is a new diagnostic discipline for in vivo imaging, which is emerging and spreading rapidly. Recent developments in molecular imaging techniques, such as positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI), allow obtaining reliable pharmacokinetic data, which can be translated into improving the permanence of the ophthalmic drugs in its action site, leading to dosage optimisation. They can be used to study either topical or intraocular administration. With these techniques it is possible to obtain real-time visualisation, localisation, characterisation and quantification of the compounds after their administration, all in a reliable, safe and non-invasive way. None of these novel techniques presents simultaneously high sensitivity and specificity, but it is possible to study biological procedures with the information provided when the techniques are combined. With the results obtained, it is possible to assume that molecular imaging techniques are postulated as a resource with great potential for the research and development of new drugs and ophthalmic delivery systems.

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Quantitative Accuracy of Low-Count SPECT Imaging in Phantom and In Vivo Mouse Studies

International Journal of Molecular Imaging ◽

10.1155/2011/197381 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Ciara M. Finucane ◽

Iain Murray ◽

Jane K. Sosabowski ◽

Julie M. Foster ◽

Stephen J. Mather

Keyword(s):

Single Photon ◽

Photon Emission ◽

Quantitative Information ◽

Emission Computed Tomography ◽

Biodistribution Studies ◽

Calibration Phantom ◽

Quantitative Accuracy ◽

Wide Range ◽

True Activity

We investigated the accuracy of a single photon emission computed tomography (SPECT) system in quantifying a wide range of radioactivity concentrations using different scan times in both phantom and animal models. A phantom containing various amounts of In-111 or Tc-99m was imaged until the activity had decayed close to background levels. Scans were acquired for different durations, employing different collimator pinhole sizes. VOI analysis was performed to quantify uptake in the images and the values compared to the true activity. The phantom results were then validated in tumour-bearing mice. The use of an appropriate calibration phantom and disabling of a background subtraction feature meant that absolute errors were within 12% of the true activity. Furthermore, a comparison of in vivo imaging and biodistribution studies in mice showed a correlation of 0.99 for activities over the 200 kBq to 5 MBq range. We conclude that the quantitative information provided by the NanoSPECT camera is accurate and allows replacement of dissection studies for assessment of radiotracer biodistribution in mouse models.

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Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

Materials ◽

10.3390/ma13030513 ◽

2020 ◽

Vol 13 (3) ◽

pp. 513 ◽

Cited By ~ 3

Author(s):

Francisco Silva ◽

António Paulo ◽

Agnès Pallier ◽

Sandra Même ◽

Éva Tóth ◽

...

Keyword(s):

Cancer Cells ◽

Cellular Uptake ◽

Photon Emission ◽

Spect Imaging ◽

Emission Computed Tomography ◽

Bimodal Imaging ◽

Biodistribution Studies ◽

T1 And T2 ◽

T2 Mri

Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1- and T2- MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1- and T2- MRI / SPECT imaging probes.

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Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer

Pharmaceutics ◽

10.3390/pharmaceutics13020182 ◽

2021 ◽

Vol 13 (2) ◽

pp. 182

Author(s):

Ayman Abouzayed ◽

Sara S. Rinne ◽

Hamideh Sabahnoo ◽

Jens Sörensen ◽

Vladimir Chernov ◽

...

Keyword(s):

Prostate Cancer ◽

Computed Tomography ◽

Single Photon ◽

Specific Binding ◽

Photon Emission ◽

Absorbed Dose ◽

Single Step ◽

Emission Computed Tomography

Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers. Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26. Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq. Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.

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The Use of Radiolabelled Human Serum Albumin and SPECT/MRI Co-Registration to Study Inflammation in The Cavernous Sinus of Cluster Headache Patients

Cephalalgia ◽

10.1111/j.1468-2982.2006.01170.x ◽

2006 ◽

Vol 26 (9) ◽

pp. 1115-1122 ◽

Cited By ~ 14

Author(s):

S Schuh-Hofer ◽

M Richter ◽

H Israel ◽

L Geworski ◽

A Villringer ◽

...

Keyword(s):

Human Serum Albumin ◽

Cluster Headache ◽

Serum Albumin ◽

Human Serum ◽

Cavernous Sinus ◽

Single Photon ◽

Photon Emission ◽

Sterile Inflammation ◽

Surrounding Tissue ◽

Emission Computed Tomography

A sterile inflammation in the cavernous sinus was hypothesized to underlie cluster headache (CH). Neurogenic inflammation is accompanied by the extravasation of plasma proteins in the surrounding tissue. We tested the hypothesis of an inflammatory process in the cavernous sinus in CH patients using 99mTc-human serum albumin (HSA) and single photon emission computed tomography (SPECT). Six patients with episodic CH were enrolled. After baseline imaging, CH attacks were induced by IV injection of nitroglycerin. The patients remained untreated for 20 min. A second SPECT was performed after successful treatment. Region of interest (ROI) analysis was performed on the basis of coregistered MRI/SPECT data. There was no statistical difference between the 99mTc-HSA uptake in the ipsilateral cavernous sinus before and after induction of an acute CH attack. There was no evidence for 99mTc-HSA extravasation in the cavernous sinus during the active episode as compared with the remission phase. Our results do not support the hypothesis of an inflammation in the cavernous sinus.

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