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Novel Molecular Imaging for Therapeutic Development
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Novel Molecular Imaging for Therapeutic Development

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 October 2021) | Viewed by 13221

Special Issue Editor

Prof. Dr. Akiva Mintz

E-Mail Website
Guest Editor
Department of Radiology, Columbia University Medical Center, New York, NY, USA
Interests: molecular imaging; drug development; PET imaging; molecular targeting; radiology

Special Issue Information

Dear Colleagues,

Molecular imaging is revolutionizing drug development. PET tracers can demonstrate kinetic and dynamics of new molecules, their receptor engagement, and downstream effects. This Special Issue aims to provide a forum for dissemination of the latest information on new approaches and methods of using molecular imaging in the drug development process.

Prof. Dr. Akiva Mintz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular imaging
  • drug development
  • PET imaging
  • molecular targeting
  • radiology

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Published Papers (3 papers)

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Research

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6 pages, 946 KiB  
Article
Granzyme B PET Imaging of the Innate Immune Response
by Kathleen M. Capaccione, Mikhail Doubrovin, Nikunj Bhatt, Akiva Mintz and Andrei Molotkov
Molecules 2020, 25(13), 3102; https://doi.org/10.3390/molecules25133102 - 7 Jul 2020
Cited by 8 | Viewed by 3623
Abstract
The human immune system is a complex system which protects against invaders and maintains tissue homeostasis. It is broadly divided into the innate and adaptive branches. Granzyme B is serine protease that plays an important role in both and can serve as a [...] Read more.
The human immune system is a complex system which protects against invaders and maintains tissue homeostasis. It is broadly divided into the innate and adaptive branches. Granzyme B is serine protease that plays an important role in both and can serve as a biomarker for cellular activation. Because of this, a granzyme B PET agent (GZP) has recently been developed and has been shown to be able to monitor response to immunotherapy. Here, we evaluated the utility of granzyme B PET imaging to assess the innate immune response. We subcutaneously administered LPS to mice to induce inflammation and performed granzyme B PET imaging after 24 and 120 h. We dissected out tissue in the region of injection and performed granzyme B immunofluorescence (IF) to confirm specificity of the GZP radiotracer. Granzyme B PET imaging demonstrated increased uptake in the region of LPS injection after 24 h, which normalized at 120 h. Granzyme B immunofluorescence showed specific staining in tissue from the 24 h time point compared to the PBS-injected control. These findings support the use of granzyme B PET for imaging innate immunity. In certain clinical contexts, the use of GZP PET imaging may be superior to currently available agents, and we therefore suggest further preclinical studies with the ultimate goal of translation to clinical use. Full article
(This article belongs to the Special Issue Novel Molecular Imaging for Therapeutic Development)
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Review

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12 pages, 27471 KiB  
Review
Progress in PET Imaging of Neuroinflammation Targeting COX-2 Enzyme
by Jaya Prabhakaran, Andrei Molotkov, Akiva Mintz and J. John Mann
Molecules 2021, 26(11), 3208; https://doi.org/10.3390/molecules26113208 - 27 May 2021
Cited by 44 | Viewed by 5211
Abstract
Neuroinflammation and cyclooxygenase-2 (COX-2) upregulation are associated with the pathogenesis of degenerative brain diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, and a response to traumatic brain injury (TBI) or stroke. COX-2 is also induced in acute [...] Read more.
Neuroinflammation and cyclooxygenase-2 (COX-2) upregulation are associated with the pathogenesis of degenerative brain diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, and a response to traumatic brain injury (TBI) or stroke. COX-2 is also induced in acute pain, depression, schizophrenia, various cancers, arthritis and in acute allograft rejection. Positron emission tomography (PET) imaging allows for the direct measurement of in vivo COX-2 upregulation and thereby enables disease staging, therapy evaluation and aid quantifying target occupancy of novel nonsteroidal anti-inflammatory drugs or NSAIDs. Thus far, no clinically useful radioligand is established for monitoring COX-2 induction in brain diseases due to the delay in identifying qualified COX-2-selective inhibitors entering the brain. This review examines radiolabeled COX-2 inhibitors reported in the past decade and identifies the most promising radioligands for development as clinically useful PET radioligands. Among the radioligands reported so far, the three tracers that show potential for clinical translation are, [11CTMI], [11C]MC1 and [18F]MTP. These radioligands demonstrated BBB permeablity and in vivo binding to constitutive COX-2 in the brain or induced COX-2 during neuroinflammation. Full article
(This article belongs to the Special Issue Novel Molecular Imaging for Therapeutic Development)
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Other

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7 pages, 1343 KiB  
Brief Report
PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains
by Naresh Damuka, Paul W. Czoty, Ashley T. Davis, Michael A. Nader, Susan H. Nader, Suzanne Craft, Shannon L. Macauley, Lindsey K. Galbo, Phillip M. Epperly, Christopher T. Whitlow, April T. Davenport, Thomas J. Martin, James B. Daunais, Akiva Mintz and Kiran Kumar Solingapuram Sai
Molecules 2020, 25(10), 2289; https://doi.org/10.3390/molecules25102289 - 13 May 2020
Cited by 9 | Viewed by 3793
Abstract
Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in [...] Read more.
Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases. Full article
(This article belongs to the Special Issue Novel Molecular Imaging for Therapeutic Development)
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