Development and Optimization of 11C-Labeled Radiotracers: A Review of the Modern Quality Control Design Process DOI
Paul Josef Myburgh, Kiran Kumar Solingapuram Sai

ACS Pharmacology & Translational Science, Год журнала: 2023, Номер 6(11), С. 1616 - 1631

Опубликована: Окт. 11, 2023

Introduction - Several 11C-tracers have demonstrated high potential in early diagnostic PET imaging applications of neurodegenerative diseases including Alzheimer's and Parkinson's disease. These radiotracers often track critical biomarkers disease pathogenesis such as tau fibrils ([11C]PBB3) or β-amyloid plaques ([11C]PiB) associated with diseases. Purpose The short review aims to serve a guideline the future development for students, postdocs and/or new radiochemists who will be synthesizing clinical grade novel research 11C-tracers, knowledge regulatory requirements. We aim bridge gap between established 11C-tracer quality control (QC) processes through exploring design process requirements 11C-pharmaceuticals. Methods A literature survey was undertaken identify articles detailed description QC methodology characterization each sections review. Overview First general summary production presented; this used establish possible places contamination assurances sterile final product. key mandated analyses use were then discussed. Further, we assessed methods reviewed routine tests preclinical translational validation studies. Therefore, both animal studies reviewed. Last, some examples optimization automation reviewed, implications practices procedures considered. Conclusion All common parameters under settings (along few exceptions) discussed detail. While it is important standard, peer-reviewed testing protocols entering umbrella, equal importance needed on address credibility repeatability study.

Язык: Английский

The role and potential of computer-aided drug discovery strategies in the discovery of novel antimicrobials DOI Creative Commons
Samson O. Oselusi, Phumuzile Dube, Adeshina I. Odugbemi

и другие.

Computers in Biology and Medicine, Год журнала: 2024, Номер 169, С. 107927 - 107927

Опубликована: Янв. 2, 2024

Antimicrobial resistance (AMR) has become more of a concern in recent decades, particularly infections associated with global public health threats. The development new antibiotics is crucial to ensuring infection control and eradicating AMR. Although drug discovery are essential processes the transformation candidate from laboratory bedside, they often very complicated, expensive, time-consuming. pharmaceutical sector continuously innovating strategies reduce research costs accelerate candidates. Computer-aided (CADD) emerged as powerful promising technology that renews hope researchers for faster identification, design, cheaper, less resource-intensive, efficient In this review, we discuss an overview AMR, potential, limitations CADD AMR discovery, case studies successful application technique rapid identification various This review will aid achieving better understanding available techniques novel candidates against resistant pathogens other infectious agents.

Язык: Английский

Процитировано

21
Optimizing Cancer Treatment: Exploring the Role of AI in Radioimmunotherapy DOI Creative Commons
Hossein Azadinejad, Mohammad Farhadi Rad, Ahmad Shariftabrizi

и другие.

Diagnostics, Год журнала: 2025, Номер 15(3), С. 397 - 397

Опубликована: Фев. 6, 2025

Radioimmunotherapy (RIT) is a novel cancer treatment that combines radiotherapy and immunotherapy to precisely target tumor antigens using monoclonal antibodies conjugated with radioactive isotopes. This approach offers personalized, systemic, durable treatment, making it effective in cancers resistant conventional therapies. Advances artificial intelligence (AI) present opportunities enhance RIT by improving precision, efficiency, personalization. AI plays critical role patient selection, planning, dosimetry, response assessment, while also contributing drug design classification. review explores the integration of into RIT, emphasizing its potential optimize entire process advance personalized care.

Язык: Английский

Процитировано

1
Efficient and Explainable Virtual Screening of Molecules through Fingerprint-Generating Networks Integrated with Artificial Neural Networks DOI Creative Commons

Rivaaj Monsia,

Sudeep Bhattacharyay

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

A machine learning-based drug screening technique has been developed and optimized using a novel, stitched neural network architecture with trainable, graph convolution-based fingerprints as base into an artificial network. The is efficient, explainable, performant tool for the binary classification of ligands based on user-chosen docking score threshold. Assessment two standardized virtual databases substantiated architecture's ability to learn molecular features substructures predict ligand classes binding affinity values more effectively than similar contemporary counterparts. Furthermore, highlight utility groups laboratories varying resources, experiments were carried out randomly sampled small molecules from ZINC database their computational scores against six drug-design relevant proteins. This new proved be efficient in that less favorably bind specific target thereby retaining top-hit molecules. Compared protocols Morgan fingerprints, fingerprint-based model shows superiority best while filtering at higher relative rate. Lastly, explainability was investigated; it revealed accurately emphasized important chemical atoms through intermediate fingerprint, which, turn, contributed heavily ultimate prediction tightly certain protein.

Язык: Английский

Процитировано

0
New strategies to enhance the efficiency and precision of drug discovery DOI Creative Commons

Qi An,

Liang Huang, Chuan Wang

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 11, 2025

Drug discovery plays a crucial role in medicinal chemistry, serving as the cornerstone for developing new treatments to address wide range of diseases. This review emphasizes significance advanced strategies, such Click Chemistry, Targeted Protein Degradation (TPD), DNA-Encoded Libraries (DELs), and Computer-Aided Design (CADD), boosting drug process. Chemistry streamlines synthesis diverse compound libraries, facilitating efficient hit lead optimization. TPD harnesses natural degradation pathways target previously undruggable proteins, while DELs enable high-throughput screening millions compounds. CADD employs computational methods refine candidate selection reduce resource expenditure. To demonstrate utility these methodologies, we highlight exemplary small molecules discovered past decade, along with summary marketed drugs investigational that exemplify their clinical impact. These examples illustrate how techniques directly contribute advancing chemistry from bench bedside. Looking ahead, Artificial Intelligence (AI) technologies interdisciplinary collaboration are poised growing complexity discovery. By fostering deeper understanding transformative this aims inspire innovative research directions further advance field chemistry.

Язык: Английский

Процитировано

0
NIH Grant Boosts Effort to Identify PET Tracers for Multiple Neurodegenerative Diseases DOI

Stacey Burling

Neurology Today, Год журнала: 2025, Номер 25(4), С. 1,19 - 23

Опубликована: Фев. 20, 2025

Язык: Английский

Процитировано

0
Structure–Activity Relationships and Evaluation of 2-(Heteroaryl-cycloalkyl)-1H-indoles as Tauopathy Positron Emission Tomography Radiotracers DOI Creative Commons
Jeffrey S. Stehouwer, Guofeng Huang,

Dinahlee Saturnino Guarino

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Structure–activity relationship studies were performed on a library of synthesized compounds based previously identified tau ligands. The top 13 new had Ki values in the range 5–14 nM Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) post-mortem brain tissues. One more promising ([3H]75) bound with high affinity AD, PSP, CBD tissues (KD's = 1–1.5 nM) Pick's tissue (KD 3.8 nM). Autoradiography [3H]75 demonstrated specific binding Nonhuman primate PET imaging [18F]75 peak standardized uptake value (SUV) ∼5 cerebellum, ∼4.5 cortex, ∼4 whole SUV 2-to-90 min ratios 3.9 brain, 4.9 4.5 cerebellum. Compound is candidate for translation to human studies.

Язык: Английский

Процитировано

0
Toward a Small-Molecule Antagonist Radioligand for Positron Emission Tomography Imaging of the Mu Opioid Receptor DOI
Konstantinos Plakas, Chia‐Ju Hsieh,

Dinahlee Saturnino Guarino

и другие.

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 29, 2025

The opioid crisis is a catastrophic health emergency catalyzed by the misuse of opioids that target and activate mu receptor. Many traditional radioligands used to study receptor are often tightly regulated owing their abuse respiratory depression potential. Of those not regulated, lack subtype selectivity can cause confounding in interpreting results. In present study, we sought design characterize library 24 antagonist ligands for Ligands were evaluated binding affinity, intrinsic activity, predicted blood-brain barrier permeability. Several demonstrated single-digit nM affinity while also demonstrating over delta kappa receptors. behavior 1A 3A at indicate these would likely induce opioid-dependent depression. Therefore, enable safer means interrogate endogenous system. Based on selectivity, potential off-target binding, [11C]1A was prepared via metallophotoredox aryl-bromide functional group [11C]methyl iodide. nascent radioligand brain uptake rhesus macaque model accumulation caudate putamen. Naloxone able reduce though interactions as pronounced naloxone's ability displace [11C]carfentanil. These results suggest GSK1521498 related congeners amenable offer way query neurobiology.

Язык: Английский

Процитировано

0
Computer-Assisted Design of Peptide-Based Radiotracers DOI Open Access
Vincenzo Patamia, Chiara Zagni,

Ilaria Brullo

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6856 - 6856

Опубликована: Апрель 6, 2023

In medical imaging, techniques such as magnetic resonance contrast-enhanced computerized tomography, positron emission tomography (PET), and single-photon computed (SPECT) are extensively available routinely used for disease diagnosis. PET probes with peptide-based targeting typically composed of small peptides especially developed to have high affinity specificity a range cellular tissue targets. These probes' key benefits include being less expensive than traditional antibody-based tracers having an effective chemical modification process that allows them be radiolabeled almost any radionuclide, making highly appealing clinical usage. Currently, every pharmaceutical design, the use in silico strategies is steadily growing this field, even though it not part standard toolkit during radiopharmaceutical design. This review describes recent applications computational design approaches novel radiopharmaceuticals.

Язык: Английский

Процитировано

9
Ligand-Based Virtual Screening as a Path to New Chemotypes for Candidate PET Radioligands for Imaging Tauopathies DOI

Bryan Hurtle,

Susovan Jana, Lisheng Cai

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(16), С. 14095 - 14109

Опубликована: Авг. 7, 2024

Ligand-based virtual screening (LBVS) has rarely been tested as a method for discovering new structural scaffolds PET radioligand development. This study used LBVS to discover potential chemotype leads developing radioligands imaging of tauopathies. ZINC12, free database over 12 million commercially available compounds, was searched novel based on similarities four query compounds. Thirteen high-ranking hits were purchased and assayed their ability compete against three tritiated at distinct binding sites in Alzheimer's disease brain tissue. Three 2-substituted 6-methoxy naphthalenes. Synthetic elaboration this yielded ligands (

Язык: Английский

Процитировано

3
Complexity of αvβ6-integrin targeting RGD peptide trimers: emergence of non-specific binding by synergistic interaction DOI Creative Commons

Neil Gerard Quigley,

Frauke Richter,

Susanne Kossatz

и другие.

RSC Medicinal Chemistry, Год журнала: 2023, Номер 14(12), С. 2564 - 2573

Опубликована: Янв. 1, 2023

Multimerization is an established strategy to design bioactive macromolecules with enhanced avidity, which has been widely employed increase the target-specific binding and uptake of imaging probes pharmaceuticals. However, factors governing general biodistribution multimeric are less well understood but nonetheless decisive for their clinical application. We found that regiospecific exchange phenylalanine by tyrosine (chemically equivalent addition single oxygen atoms) can have unexpected, dramatic impact on in vivo behavior gallium-68 labeled αvβ6-integrin peptides trimers. For example, introduction one two Tyr, just 1 2 additional oxygens molecular weight increases 0.38% 0.76% our >4 kDa constructs, reduced non-specific liver 50% 72%, respectively. The observed effect did not correlate polarity measures such as log D, generally defies explanation reductionist approaches. conclude multimers should be viewed combinations whose properties simply add up, whole entities higher intrinsic complexity thus a strong tendency exhibit newly emerged that, principle, cannot predicted from characteristics monomers used.

Язык: Английский

Процитировано

7