Ocular Biodistribution Studies Using Molecular Imaging

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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Recent Advances in Targeting Nuclear Molecular Imaging Driven by Tetrazine Bioorthogonal Chemistry

Current Medicinal Chemistry ◽

10.2174/1386207322666190702105829 ◽

2020 ◽

Vol 27 (23) ◽

pp. 3924-3943 ◽

Cited By ~ 1

Author(s):

Ping Dong ◽

Xueyi Wang ◽

Junwei Zheng ◽

Xiaoyang Zhang ◽

Yiwen Li ◽

...

Keyword(s):

Molecular Imaging ◽

Single Photon ◽

Imaging Techniques ◽

Photon Emission ◽

Emission Computed Tomography ◽

Bioorthogonal Chemistry ◽

Cellular Processes ◽

Positron Emission ◽

Diagnosis Of Cancer

Molecular imaging techniques apply sophisticated technologies to monitor, directly or indirectly, the spatiotemporal distribution of molecular or cellular processes for biomedical, diagnostic, or therapeutic purposes. For example, Single-Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) imaging, the most representative modalities of molecular imaging, enable earlier and more accurate diagnosis of cancer and cardiovascular diseases. New possibilities for noninvasive molecular imaging in vivo have emerged with advances in bioorthogonal chemistry. For example, tetrazine-related Inverse Electron Demand Diels-Alder (IEDDA) reactions can rapidly generate short-lived radioisotope probes in vivo that provide strong contrast for SPECT and PET. Here, we review pretargeting strategies for molecular imaging and novel radiotracers synthesized via tetrazine bioorthogonal chemistry. We systematically describe advances in direct radiolabeling and pretargeting approaches in SPECT and PET using metal and nonmetal radioisotopes based on tetrazine bioorthogonal reactions, and we discuss prospects for the future of such contrast agents.

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Radionuclide-Based Imaging of Breast Cancer: State of the Art

Cancers ◽

10.3390/cancers13215459 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5459

Author(s):

Huiling Li ◽

Zhen Liu ◽

Lujie Yuan ◽

Kevin Fan ◽

Yongxue Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Single Photon ◽

Morphological Changes ◽

Imaging Techniques ◽

Rapid Development ◽

Photon Emission ◽

Emission Computed Tomography ◽

Biological Processes ◽

Functional Perspective

Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.

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Imaging Amyloid-β Deposits In Vivo

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200209000-00001 ◽

2002 ◽

Vol 22 (9) ◽

pp. 1035-1041 ◽

Cited By ~ 76

Author(s):

Brian J. Bacskai ◽

William E. Klunk ◽

Chester A. Mathis ◽

Bradley T. Hyman

Keyword(s):

Single Photon ◽

Senile Plaques ◽

Photon Emission ◽

Multiphoton Microscopy ◽

Amyloid Β ◽

Neuronal Loss ◽

High Sensitivity ◽

Emission Computed Tomography ◽

Tissue Samples

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-β plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-β plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-β deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-β deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-β with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.

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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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Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging

International Journal of Molecular Sciences ◽

10.3390/ijms20123047 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3047 ◽

Cited By ~ 6

Author(s):

Vorobyeva ◽

Schulga ◽

Rinne ◽

Günther ◽

Orlova ◽

...

Keyword(s):

Molecular Imaging ◽

Single Photon ◽

Photon Emission ◽

Growth Factor Receptor ◽

Emission Computed Tomography ◽

Rapid Clearance ◽

Epidermal Growth ◽

Ankyrin Repeat Proteins ◽

Monitor Treatment Response

Radionuclide molecular imaging of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal cancer might be used to stratify patients for HER2-targeted therapy as well as monitor treatment response and disease progression. Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins with favorable properties for molecular imaging. Herein we compared two methods for labeling the anti-HER2 DARPin (HE)3-G3, direct and indirect radioiodination. We hypothesized that the use of N-succinimidyl-para-iodobenzoate (SPIB) for radioiodination would facilitate the clearance of radiometabolites and improve the contrast of imaging. Both radiolabeled (HE)3-G3 variants preserved their binding specificity and high affinity to HER2-expressing cells. The specificity of tumor targeting in vivo was also demonstrated. A biodistribution comparison of [125I]I-(HE)3-G3 and [125I]I-PIB-(HE)3-G3, in mice bearing HER2 expressing SKOV3 xenografts, showed rapid clearance of [125I]I-PIB-(HE)3-G3 from normal organs and tissues and low accumulation of activity in organs with NaI-symporter expression. Both radiolabeled (HE)3-G3 variants had equal tumor uptake. Consequently, the indirect label provided higher tumor-to-blood and tumor-to-organ ratios compared with the direct label. Comparative Single Photon Emission Computed Tomography (SPECT)/CT imaging of HER2 expression in SKOV3 xenografts, using both radiolabeled DARPins, demonstrated the superior imaging contrast of the indirect label. Indirect radioiodination of (HE)3-G3 using SPIB could be further applied for SPECT and PET imaging with iodine-123 and iodine-124.

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Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

BioMed Research International ◽

10.1155/2017/5246853 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Jinhui Li ◽

Jing Lu ◽

You Zhou

Keyword(s):

Molecular Imaging ◽

Cardiac Disease ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Positron Emission ◽

Molecular Imaging Probes ◽

Imaging Probes ◽

Targeted Molecular Imaging

The present study aimed to discuss the role of mitochondrion in cardiac function and disease. The mitochondrion plays a fundamental role in cellular processes ranging from metabolism to apoptosis. The mitochondrial-targeted molecular imaging could potentially illustrate changes in global and regional cardiac dysfunction. The collective changes that occur in mitochondrial-targeted molecular imaging probes have been widely explored and developed. As probes currently used in the preclinical setting still have a lot of shortcomings, the development of myocardial metabolic activity, viability, perfusion, and blood flow molecular imaging probes holds great potential for accurately evaluating the myocardial viability and functional reserve. The advantages of molecular imaging provide a perspective on investigating the mitochondrial function of the myocardium in vivo noninvasively and quantitatively. The molecular imaging tracers of single-photon emission computed tomography and positron emission tomography could give more detailed information on myocardial metabolism and restoration. In this study, series mitochondrial-targeted99mTc-,123I-, and18F-labeled tracers displayed broad applications because they could provide a direct link between mitochondrial dysfunction and cardiac disease.

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Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of Scans Without Evidence of Dopaminergic Deficit (SWEDDs)

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2012000900004 ◽

2012 ◽

Vol 70 (9) ◽

pp. 667-673 ◽

Cited By ~ 12

Author(s):

Marco A. T. Utiumi ◽

André C. Felício ◽

Conrado R. Borges ◽

Vera L. Braatz ◽

Sheyla A. S. Rezende ◽

...

Keyword(s):

Dopamine Transporter ◽

Single Photon ◽

Imaging Techniques ◽

Photon Emission ◽

Cost Effective ◽

Emission Computed Tomography ◽

Parkinsonian Syndromes ◽

Cost Effective Technique ◽

Dat Spect

The clinical diagnosis of Parkinson's disease (PD) is susceptible to misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo imaging techniques assessing the presynaptic dopamine transporter (DAT) have emerged as a useful tool in PD diagnosis, improving its accuracy. OBJECTIVE: It was to illustrate the clinical usefulness of a brain single-photon emission computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans without evidence of dopaminergic deficit (SWEDDs) in this context. CASES: We described four representative patients with clinically unclear parkinsonian syndromes who underwent [99mTc]-TRODAT-1 SPECT and reviewed the clinical implications. CONCLUSION: DAT-SPECT is an important, cost-effective, technique for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD cases present clinical and paraclinical peculiarities that may retrospectively identify them as essential/dystonic tremor. The lack of histopathological data limits further conclusions.

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Molecular Imaging: Implications for Oral Cancer

World Journal of Dentistry ◽

10.5005/jp-journals-10015-1006 ◽

2010 ◽

Vol 1 (1) ◽

pp. 31-34

Author(s):

Shubhasini A Raghavan

Keyword(s):

Computed Tomography ◽

Molecular Imaging ◽

Oral Cancer ◽

Single Photon ◽

Indian Subcontinent ◽

Imaging Techniques ◽

Photon Emission ◽

Active Role ◽

Emission Computed Tomography ◽

World Population

ABSTRACT Cancer is a scourge that affects millions of the world population. The incidence of oral cancer is alarmingly high in the Indian subcontinent. What is more appalling is the low survival rate of these patients. Various efforts are being made to bring about early diagnosis, accurate staging and aggressive treatment. Molecular imaging is one step in this direction. Today, imaging plays a role not just in detecting what is radiopaque and what is radiolucent, but also plays a very active role in detecting disease down to the level of a single cell. The field of molecular imaging has been defined as ‘the visualization, characterization, and measurement of biologic processes at molecular and cellular levels in humans and other living systems’. The amalgamation of advanced imaging techniques such as Positron Emission Tomography and Single Photon Emission Computed Tomography with Computed Tomography, the use of newer contrast agents, incorporation of nanoparticles all have brought about these revolutionary changes in imaging. The purpose of this article is to describe the various techniques used in molecular imaging specifically highlighting their application in head and neck cancer.

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Radiolabeling of Nucleic Acid Aptamers for Highly Sensitive Disease-Specific Molecular Imaging

Pharmaceuticals ◽

10.3390/ph11040106 ◽

2018 ◽

Vol 11 (4) ◽

pp. 106 ◽

Cited By ~ 8

Author(s):

Leila Hassanzadeh ◽

Suxiang Chen ◽

Rakesh Veedu

Keyword(s):

Molecular Imaging ◽

Single Photon ◽

Imaging Techniques ◽

Photon Emission ◽

Three Dimensional ◽

Nuclear Imaging ◽

Spect Imaging ◽

Emission Computed Tomography ◽

Nuclear Medicine Imaging ◽

Highly Sensitive

Aptamers are short single-stranded DNA or RNA oligonucleotide ligand molecules with a unique three-dimensional shape, capable of binding to a defined molecular target with high affinity and specificity. Since their discovery, aptamers have been developed for various applications, including molecular imaging, particularly nuclear imaging that holds the highest potential for the clinical translation of aptamer-based molecular imaging probes. Their easy laboratory production without any batch-to-batch variations, their high stability, their small size with no immunogenicity and toxicity, and their flexibility to incorporate various functionalities without compromising the target binding affinity and specificity make aptamers an attractive class of targeted-imaging agents. Aptamer technology has been utilized in nuclear medicine imaging techniques, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), as highly sensitive and accurate biomedical imaging modalities towards clinical diagnostic applications. However, for aptamer-targeted PET and SPECT imaging, conjugation of appropriate radionuclides to aptamers is crucial. This review summarizes various strategies to link the radionuclides to chemically modified aptamers to accomplish aptamer-targeted PET and SPECT imaging.

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Recent Progress in Technetium-99m-Labeled Nanoparticles for Molecular Imaging and Cancer Therapy

Nanomaterials ◽

10.3390/nano11113022 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3022

Author(s):

Sajid Mushtaq ◽

Asia Bibi ◽

Jung Eun Park ◽

Jongho Jeon

Keyword(s):

Drug Delivery ◽

Molecular Imaging ◽

Cancer Therapy ◽

Single Photon ◽

Photon Emission ◽

Whole Body ◽

Emission Computed Tomography ◽

Technetium 99M ◽

Approved Drugs

Nanotechnology has played a tremendous role in molecular imaging and cancer therapy. Over the last decade, scientists have worked exceptionally to translate nanomedicine into clinical practice. However, although several nanoparticle-based drugs are now clinically available, there is still a vast difference between preclinical products and clinically approved drugs. An efficient translation of preclinical results to clinical settings requires several critical studies, including a detailed, highly sensitive, pharmacokinetics and biodistribution study, and selective and efficient drug delivery to the target organ or tissue. In this context, technetium-99m (99mTc)-based radiolabeling of nanoparticles allows easy, economical, non-invasive, and whole-body in vivo tracking by the sensitive clinical imaging technique single-photon emission computed tomography (SPECT). Hence, a critical analysis of the radiolabeling strategies of potential drug delivery and therapeutic systems used to monitor results and therapeutic outcomes at the preclinical and clinical levels remains indispensable to provide maximum benefit to the patient. This review discusses up-to-date 99mTc radiolabeling strategies of a variety of important inorganic and organic nanoparticles and their application to preclinical imaging studies.

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