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

2019 ◽  
Vol 20 (12) ◽  
pp. 3047 ◽  
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.

scholarly journals Ocular Biodistribution Studies Using Molecular Imaging

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 237 ◽  
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.

scholarly journals Mitochondrial-Targeted Molecular Imaging in Cardiac Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
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.

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

Nanomaterials ◽  
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.

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

2020 ◽  
Vol 27 (23) ◽  
pp. 3924-3943 ◽  
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.

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.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 770
Author(s):  
Patrick M. Perrigue ◽  
Richard A. Murray ◽  
Angelika Mielcarek ◽  
Agata Henschke ◽  
Sergio E. Moya
Keyword(s):  
Drug Delivery ◽  
Laser Scanning ◽  
Single Photon ◽  
Photon Emission ◽  
Correlation Spectroscopy ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Emission Computed Tomography ◽  
Systemic Delivery

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

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