Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Insight into the Development of PET Radiopharmaceuticals for Oncology.

ABSTRACT: While the development of positron emission tomography (PET) radiopharmaceuticals closely follows that of traditional drug development, there are several key considerations in the chemical and radiochemical synthesis, preclinical assessment, and clinical translation of PET radiotracers. As such, we outline the fundamentals of radiotracer design, with respect to the selection of an appropriate pharmacophore. These concepts will be reinforced by exemplary cases of PET radiotracer development, both with respect to their preclinical and clinical evaluation. We also provide a guideline for the proper selection of a radionuclide and the appropriate labeling strategy to access a tracer with optimal imaging qualities. Finally, we summarize the methodology of their evaluation in in vitro and animal models and the road to clinical translation. This review is intended to be a primer for newcomers to the field and give insight into the workflow of developing radiopharmaceuticals.

SUBMITTER: Lau J

PROVIDER: S-EPMC7281377 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Insight into the Development of PET Radiopharmaceuticals for Oncology.

Lau Joseph J Rousseau Etienne E Kwon Daniel D Lin Kuo-Shyan KS Bénard François F Chen Xiaoyuan X

Cancers 20200521 5

While the development of positron emission tomography (PET) radiopharmaceuticals closely follows that of traditional drug development, there are several key considerations in the chemical and radiochemical synthesis, preclinical assessment, and clinical translation of PET radiotracers. As such, we outline the fundamentals of radiotracer design, with respect to the selection of an appropriate pharmacophore. These concepts will be reinforced by exemplary cases of PET radiotracer development, both ...[more]

PMID: 32455729

Similar Datasets

New SPECT and PET radiopharmaceuticals for imaging cardiovascular disease.

Project description:Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI) continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.

| S-EPMC4034657 | biostudies-other

Methods to Enhance the Metabolic Stability of Peptide-Based PET Radiopharmaceuticals.

Project description:The high affinity and specificity of peptides towards biological targets, in addition to their favorable pharmacological properties, has encouraged the development of many peptide-based pharmaceuticals, including peptide-based positron emission tomography (PET) radiopharmaceuticals. However, the poor in vivo stability of unmodified peptides against proteolysis is a major challenge that must be overcome, as it can result in an impractically short in vivo biological half-life and a subsequently poor bioavailability when used in imaging and therapeutic applications. Consequently, many biologically and pharmacologically interesting peptide-based drugs may never see application. A potential way to overcome this is using peptide analogues designed to mimic the pharmacophore of a native peptide while also containing unnatural modifications that act to maintain or improve the pharmacological properties. This review explores strategies that have been developed to increase the metabolic stability of peptide-based pharmaceuticals. It includes modifications of the C- and/or N-termini, introduction of d- or other unnatural amino acids, backbone modification, PEGylation and alkyl chain incorporation, cyclization and peptide bond substitution, and where those strategies have been, or could be, applied to PET peptide-based radiopharmaceuticals.

| S-EPMC7287708 | biostudies-literature

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives.

Project description:Rhenium-188 (188Re) is a high energy beta-emitting radioisotope with a short 16.9 h physical half-life, which has been shown to be a very attractive candidate for use in therapeutic nuclear medicine. The high beta emission has an average energy of 784 keV and a maximum energy of 2.12 MeV, sufficient to penetrate and destroy targeted abnormal tissues. In addition, the low-abundant gamma emission of 155 keV (15%) is efficient for imaging and for dosimetric calculations. These key characteristics identify 188Re as an important therapeutic radioisotope for routine clinical use. Moreover, the highly reproducible on-demand availability of 188Re from the 188W/188Re generator system is an important feature and permits installation in hospital-based or central radiopharmacies for cost-effective availability of no-carrier-added (NCA) 188Re. Rhenium-188 and technetium-99 m exhibit similar chemical properties and represent a "theranostic pair." Thus, preparation and targeting of 188Re agents for therapy is similar to imaging agents prepared with 99mTc, the most commonly used diagnostic radionuclide. Over the last three decades, radiopharmaceuticals based on 188Re-labeled small molecules, including peptides, antibodies, Lipiodol and particulates have been reported. The successful application of these 188Re-labeled therapeutic radiopharmaceuticals has been reported in multiple early phase clinical trials for the management of various primary tumors, bone metastasis, rheumatoid arthritis, and endocoronary interventions. This article reviews the use of 188Re-radiopharmaceuticals which have been investigated in patients for cancer treatment, demonstrating that 188Re represents a cost effective alternative for routine clinical use in comparison to more expensive and/or less readily available therapeutic radioisotopes.

| S-EPMC6587137 | biostudies-literature

Two Novel PET Radiopharmaceuticals for Endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1) Targeting.

Project description:Atherosclerosis is a chronic progressive disease involving inflammatory events, such as the overexpression of adhesion molecules including the endothelial Vascular Cell Adhesion Molecule-1 (VCAM-1). VCAM-1 is rapidly overexpressed in the first stages of atherosclerosis, thus representing a promising target for early atheroma detection. Two novel Positron Emission Tomography (PET) radiopharmaceuticals (MacroP and NAMP), based on the VCAM-1-binding peptide having sequence VHPKQHRGGSKGC, were synthesized and characterized. MacroP is derived from the direct conjugation of a DOTA derivative with the peptide, while NAMP is a biotin derivative conceived to be employed in a three-step pretargeting system, involving the use of a double-chelating derivative of DOTA. The identity of the newly synthesized radiopharmaceuticals was confirmed by mass spectrometry and, after radiolabeling with 68Ga, both showed high radiochemical purity; in vitro tests on human umbilical vein endothelial cells evidenced their VCAM-1 binding ability, with higher radioactive uptake in the case of NAMP. Moreover, NAMP might also be employed in a theranostic approach in association with functionalized biotinylated nanoparticles.

| S-EPMC8309178 | biostudies-literature

Towards enhanced PET quantification in clinical oncology.

Project description:Positron emission tomography (PET) has, since its inception, established itself as the imaging modality of choice for the in vivo quantitative assessment of molecular targets in a wide range of biochemical processes underlying tumour physiology. PET image quantification enables to ascertain a direct link between the time-varying activity concentration in organs/tissues and the fundamental parameters portraying the biological processes at the cellular level being assessed. However, the quantitative potential of PET may be affected by a number of factors related to physical effects, hardware and software system specifications, tracer kinetics, motion, scan protocol design and limitations in current image-derived PET metrics. Given the relatively large number of PET metrics reported in the literature, the selection of the best metric for fulfilling a specific task in a particular application is still a matter of debate. Quantitative PET has advanced elegantly during the last two decades and is now reaching the maturity required for clinical exploitation, particularly in oncology where it has the capability to open many avenues for clinical diagnosis, assessment of response to treatment and therapy planning. Therefore, the preservation and further enhancement of the quantitative features of PET imaging is crucial to ensure that the full clinical value of PET imaging modality is utilized in clinical oncology. Recent advancements in PET technology and methodology have paved the way for faster PET acquisitions of enhanced sensitivity to support the clinical translation of highly quantitative four-dimensional (4D) parametric imaging methods in clinical oncology. In this report, we provide an overview of recent advances and future trends in quantitative PET imaging in the context of clinical oncology. The pros/cons of the various image-derived PET metrics will be discussed and the promise of novel methodologies will be highlighted.

| S-EPMC6049841 | biostudies-other

Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals.

Project description:Metallic radionuclides are the mainstay of both diagnostic and therapeutic radiopharmaceuticals. Therapeutic nuclear medicine is less advanced but has tremendous potential if the radionuclide is accurately targeted. Great interest exists in the field of inorganic chemistry for developing target specific radiopharmaceuticals based on radiometals for non-invasive disease detection and cancer radiotherapy. This perspective will focus on the nuclear properties of a few important radiometals and their recent applications to developing radiopharmaceuticals for imaging and therapy. Other topics for discussion will include imaging techniques, radiotherapy, analytical techniques, and radiation safety. The ultimate goal of this perspective is to introduce inorganic chemists to the field of nuclear medicine and radiopharmaceutical development, where many applications of fundamental inorganic chemistry can be found.

| S-EPMC3716284 | biostudies-literature

Diagnostic Performance of PET Imaging Using Different Radiopharmaceuticals in Prostate Cancer According to Published Meta-Analyses.

Project description:A significant number of meta-analyses reporting data on the diagnostic performance of positron emission tomography (PET) in prostate cancer (PCa) is currently available in the literature. In particular, different PET radiopharmaceuticals were used for this purpose. The aim of this review is to summarize information retrieved by published meta-analyses on this topic. The first step included a systematic search of the literature (last search date: June 2020), screening two databases (PubMed/MEDLINE and Cochrane Library). This combination of key words was used: (A) "PET" OR "positron emission tomography" AND (B) "prostate" OR "prostatic" AND (C) meta-analysis. Only meta-analyses on Positron Emission Tomography/Computed Tomography (PET/CT) or Positron Emission Tomography/Magnetic Resonance (PET/MR) in PCa were selected. We have summarized the diagnostic performance of PET imaging in PCa, taking into account 39 meta-analyses published in the literature. Evidence-based data showed the good diagnostic performance of PET/CT with several radiopharmaceuticals, including prostate-specific membrane antigen (PSMA)-targeted agents, radiolabeled choline, fluciclovine, and fluoride in restaging and staging settings. Less evidence-based data were available for PET/MR with different radiotracers. More prospective multicentric studies and cost-effectiveness analyses are warranted.

| S-EPMC7463824 | biostudies-literature

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis

Project description:Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3–99.9%), specificity 91.2% (95% CI: 68.4–98.1%), LR+ 4.5 (95% CI: 2.2–9.3), LR− 0.07 (95% CI: 0.04–0.15), and DOR 70.1 (95% CI: 19.6–250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

| S-EPMC9323081 | biostudies-literature

Patient-Reported Adverse Events of Radiopharmaceuticals: Development and Validation of a Questionnaire.

Project description:INTRODUCTION:Radiopharmaceuticals may cause adverse events. Knowledge about adverse events from a patient's perspective could help healthcare professionals to detect, understand, and manage adverse events more efficiently when using radiopharmaceuticals. Researchers need a validated questionnaire that can be used in patients to assess adverse events with radiopharmaceuticals. OBJECTIVE:The aim of this study was to develop, validate the content of, and perform initial testing of a questionnaire assessing patient-reported adverse events of radiopharmaceuticals. METHODS:Based on existing literature, six professionals drafted and evaluated a first version of the questionnaire. Further content validation was performed using cognitive interviews with six patients undergoing a nuclear medicine examination. After adaptations, the questionnaire was developed into a web-based questionnaire. One hundred patients undergoing nuclear examination tested this version, and the results were used to assess its acceptability and evaluate reported adverse events. RESULTS:Questions and answer options were revised in the initial questionnaire to improve clarity. In addition, some questions were removed. The final version consisted of 18 questions. In the test phase, the acceptability of the questionnaire was demonstrated (e.g. 79% of the patients who received the questionnaire completed it, and the median time to complete the questionnaire was 12 min for patients who reported an adverse event). Of the 100 patients (53% men, median age 64 years), 12 reported a total of 22 adverse events. One of these adverse events had a high causal association. CONCLUSION:After validation and testing, the developed questionnaire to study patient-reported adverse events of radiopharmaceuticals is a suitable and valid instrument which can be used in future research.

| S-EPMC7105441 | biostudies-literature

Recent advances of PET imaging in clinical radiation oncology.

Project description:Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.

| S-EPMC7171749 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data