Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging.

(acetylacetonato)oxidovanadium(IV) [(VO(acac)], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (V) generated with a compact medical cyclotron has been used to label VO(acac) as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac) require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis.

Evaluation of an Image-Derived Input Function for Kinetic Modeling of Nicotinic Acetylcholine Receptor-Binding PET Ligands in Mice.

Positron emission tomography (PET) radioligands that bind with high-affinity to α4β2-type nicotinic receptors (α4β2Rs) allow for in vivo investigations of the mechanisms underlying nicotine addiction and smoking cessation. Here, we investigate the use of an image-derived arterial input function and the cerebellum for kinetic analysis of radioligand binding in mice. Two radioligands were explored: 2-[F]FA85380 (2-FA), displaying similar pKa and binding affinity to the smoking cessation drug varenicline (Chantix), and [F]Nifene, displaying similar pKa and binding affinity to nicotine.

A simplified protocol for the automated production of 2-[ F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ([ F]nifene) on an IBA Synthera® module.

The α4β2 nicotinic acetylcholine receptor (nAChR) ligand 2-[ F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ([ F]nifene) has been synthesized in 10% decay-corrected radiochemical yield using the IBA Synthera® platform (IBA Cyclotron Solutions, Louvain-la-Neuve, Belgium) with an integrated fluidic processor (IFP). Boc-nitronifene served as the precursor, and 20% trifluoroacetic acid (TFA) was used to deprotect the Boc-group after radiolabeling. By omitting the solvent extraction step after radiolabeling, the process was simplified to a single step with no manual intervention.

Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics.

In the field of nuclear medicine, the β -emitting Sc and β -emitting Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for Sc than for other proposed true theranostics. Before Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope's radiolabeling and animal imaging capabilities studied with a widely utilized tracer.

Modelling cyclotron-based production of radioisotopes via TOPAS.

. In this work, the irradiation of natural titanium foils in the beam-stop of a compact medical cyclotron, an IBA CYCLONE 18/9, is simulated to assess the efficacy of using a beam-stop as a target holder, and using two different target geometries, in the production of vanadium-48, a positron-emitting radioisotope with potential utility as a cancer imaging agent in positron emission tomography..

Trapping of Nicotinic Acetylcholine Receptor Ligands Assayed by Cellular Studies and PET Imaging.

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membrane-permeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pK and high affinity for α4β2-type nicotinic receptors (α4β2Rs) are trapped in intracellular acidic vesicles containing α4β2Rs Nicotine, with lower pK and α4β2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligands in male and female mouse brain and identifying the trapping brain organelle as Golgi satellites (GSats).

The optimal F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO electron paramagnetic resonance imaging as reference truth.

Purpose: To identify the optimal threshold in F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO EPRI) as ground truth for hypoxia, defined by pO [Formula: see text] 10 mmHg.

Methods: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue.

Preliminary investigation of V-labeled VO(acac) for cancer imaging: An initial proof-of-concept study.

In this preliminary study, a procedure for synthesizing novel PET radiotracer vanadium-48-labeled-vanadyl acetylacetonate was developed, including radioisotope production via cyclotron, separation of V, chelation as VO(acac), and assessment through in vitro cellular studies. We employed the beam-stop setup in a cyclotron as the target holder to irradiate titanium foils in the reaction of Ti (p,n)V. The radioisotope production rate was 4.

Improving Tumor Hypoxia Location in F-Misonidazole PET with Dynamic Contrast-enhanced MRI Using Quantitative Electron Paramagnetic Resonance Partial Oxygen Pressure Images.

Purpose: To enhance the spatial accuracy of fluorine 18 (F) misonidazole (MISO) PET imaging of hypoxia by using dynamic contrast-enhanced (DCE) MR images as a basis for modifying PET images and by using electron paramagnetic resonance (EPR) partial oxygen pressure (pO) as the reference standard.

Materials And Methods: Mice ( = 10) with leg-borne MCa4 mammary carcinomas underwent EPR imaging, T2-weighted and DCE MRI, and F-MISO PET/CT. Images were registered to the same space for analysis.

In Vivo Imaging of the Tumor-Associated Enzyme NCEH1 with a Covalent PET Probe.

Herein, we report the development of an F-labeled, activity-based small-molecule probe targeting the cancer-associated serine hydrolase NCEH1. We undertook a focused medicinal chemistry campaign to simultaneously preserve potent and specific NCEH1 labeling in live cells and animals, while permitting facile F radionuclide incorporation required for PET imaging. The resulting molecule, [ F]JW199, labels active NCEH1 in live cells at nanomolar concentrations and greater than 1000-fold selectivity relative to other serine hydrolases.

Development of a PET radioligand for potassium channels to image CNS demyelination.

Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET).

Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases.

3-[F]fluoro-4-aminopyridine, [F]3F4AP, is a radiofluorinated analog of the FDA-approved drug for multiple sclerosis 4-aminopyridine (4AP). This compound is currently under investigation as a PET tracer for demyelination. We recently described a novel chemical reaction to produce metafluorinated pyridines consisting of direct fluorination of a pyridine N-oxide and the utilization of this reaction for the radiochemical synthesis of [F]3F4AP.

A novel approach to measuring macrophage-specific reverse cholesterol transport in vivo in humans.

Reverse cholesterol transport (RCT) is thought to be an atheroprotective function of HDL, and macrophage-specific RCT in mice is inversely associated with atherosclerosis. We developed a novel method using H-cholesterol nanoparticles to selectively trace macrophage-specific RCT in vivo in humans. Use of H-cholesterol nanoparticles was initially tested in mice to assess the distribution of tracer and response to interventions known to increase RCT.

A Dedicated Breast Positron Emission Tomography Scanner: Proof of Concept.

Purpose: This study developed and tested a novel scanner constructed for dedicated positron emission tomography (PET) of the breast. The breast PET (B-PET) scanner is designed with two opposing detectors using curve plate NaI(Tl) detectors to achieve a combination of high spatial resolution and energy resolution.

Methods: Phantom and clinical studies (n = 20) with F-fluorodeoxyglucose were carried out on the whole-body Philips Allegro scanner and the B-PET scanner.

Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma.

Purpose: The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of (18)F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of (18)F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies.

Methods: (18)F-EF5 was synthesized by electrophilic addition of (18)F(2) gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus.

The radiation response of cells from 9L gliosarcoma tumours is correlated with [F18]-EF5 uptake.

Purpose: Tumour hypoxia affects cancer biology and therapy-resistance in both animals and humans. The purpose of this study was to determine whether EF5 ([2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide]) binding and/or radioactive drug uptake correlated with single-dose radiation response in 9L gliosarcoma tumours.

Materials And Methods: Twenty-two 9L tumours were grown in male Fischer rats.

Dosimetry of 11C-carfentanil, a micro-opioid receptor imaging agent.

Objective: 11C-carfentanil is a radiopharmaceutical that selectively binds the mu-opiate receptor of the central nervous system. However, its dosimetry throughout the body and other organs has never been reported in the literature. The purpose of this study was to measure the radiation dosimetry of 11C-carfentanil in healthy human volunteers.

Comparison of diffuse optical tomography of human breast with whole-body and breast-only positron emission tomography.

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities.

Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism.

Objectives: Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18F-fluoro-l-dihydroxyphenylalanine ([18F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions.

Diagnosis and localization of focal congenital hyperinsulinism by 18F-fluorodopa PET scan.

Objectives: To assess the accuracy of 18F-fluoro-L-dihydroxyphenylalanine ([18F]-DOPA) PET scans to diagnose focal versus diffuse disease and to localize focal lesions in infants with congenital hyperinsulinism.

Study Design: Twenty-four infants with hyperinsulinism unresponsive to medical therapy were studied. Patients were injected intravenously with [18F]-DOPA, and PET scans were obtained for 1 hour.

Performance of a brain PET camera based on anger-logic gadolinium oxyorthosilicate detectors.

Unlabelled: A high-sensitivity, high-resolution brain PET scanner ("G-PET") has been developed. This scanner is similar in geometry to a previous brain scanner developed at the University of Pennsylvania, the HEAD Penn-PET, but the detector technology and electronics have been improved to achieve enhanced performance.

Methods: This scanner has a detector ring diameter of 42.