PET imaging of focused-ultrasound enhanced delivery of AAVs into the murine brain.

Despite recent advances in the use of adeno-associated viruses (AAVs) as potential vehicles for genetic intervention of central and peripheral nervous system-associated disorders, gene therapy for the treatment of neuropathology in adults has not been approved to date. The currently FDA-approved AAV-vector based gene therapies rely on naturally occurring serotypes, such as AAV2 or AAV9, which display limited or no transport across the blood-brain barrier (BBB) if systemically administered. Recently developed engineered AAV variants have shown broad brain transduction and reduced off-target liver toxicity in non-human primates (NHPs).

Clinical Radiosynthesis and Translation of [F]OP-801: A Novel Radiotracer for Imaging Reactive Microglia and Macrophages.

Positron emission tomography (PET) is a powerful tool for studying neuroinflammatory diseases; however, current PET biomarkers of neuroinflammation possess significant limitations. We recently reported a promising dendrimer PET tracer ([F]OP-801), which is selectively taken up by reactive microglia and macrophages. Here, we describe further important characterization of [F]OP-801 in addition to optimization and validation of a two-step clinical radiosynthesis.

Preclinical Evaluation of Zr-Panitumumab for Biology-Guided Radiation Therapy.

Purpose: Biology-guided radiation therapy (BgRT) uses real-time line-of-response data from on-board positron emission tomography (PET) detectors to guide beamlet delivery during therapeutic radiation. The current workflow requires F-fluorodeoxyglucose (FDG) administration daily before each treatment fraction. However, there are advantages to reducing the number of tracer injections by using a PET tracer with a longer decay time.

Development and biological evaluation of[F]FMN3PA & [F]FMN3PU for leucine-rich repeat kinase 2 (LRRK2) in vivo PET imaging.

Purpose: Among all genetic mutations of LRRK2, the G2019S mutation is the most commonly associated with the late-onset of Parkinson's disease (PD). Hence, one potential therapeutic approach is to block the hyperactivity of mutated LRRK2 induced by kinase inhibition. To date, only a few LRRK2 kinase inhibitors have been tested for in vivo quantification of target engagement by positron emission tomography (PET).

Lewis Acid-Facilitated Radiofluorination of MN3PU: A LRRK2 Radiotracer.

Background: Temperature-sensitive radiopharmaceutical precursors require lower reaction temperatures (<100 °C) during nucleophilic radiofluorination in order to avoid compound thermolysis, often resulting in sub-optimal radiochemical yields (RCYs). To facilitate nucleophilic aromatic substitution (SAr) of nucleofuges commonly used in radiofluorination (e.g.

PET imaging study of brown adipose tissue (BAT) activity in mice devoid of receptor for advanced glycation end products (RAGE).

Brown adipose tissue (BAT) is responsible for adaptive thermogenesis. We previously showed that genetic deficiency of receptor for advanced glycation end products (RAGE) prevented the effects of high-fat diet (HFD). This study was to compare BAT activity in RAGE knock out (Ager, RKO) and wild-type (WT) mice after treated with HFD or LFD.

F-Branched-Chain Amino Acids: Structure-Activity Relationships and PET Imaging Potential.

The large, neutral L-type amino acid transporters (LAT1-LAT4) are sodium-independent transporters that are widely distributed throughout the body. LAT expression levels are increased in many types of cancer, and their expression increases as cancers progress, leading to high expression levels in high-grade tumors and metastases. Because of the key role and overexpression of LAT in many types of cancer, radiolabeled LAT substrates are promising candidates for nuclear imaging of malignancies that are not well revealed by conventional radiotracers.

Site-Selective, Late-Stage C-H F-Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging.

Peptides are often ideal ligands for diagnostic molecular imaging due to their ease of synthesis and tuneable targeting properties. However, labelling unmodified peptides with F for positron emission tomography (PET) imaging presents a number of challenges. Here we show the combination of photoactivated sodium decatungstate and [ F]-N-fluorobenzenesulfonimide effects site-selective F-fluorination at the branched position in leucine residues in unprotected and unaltered peptides.

Heavy Metals in Selected Vegetables from Markets of Faisalabad, Pakistan.

Two hundred ten samples of selected vegetables (okra, pumpkin, tomato, potato, eggplant, spinach, and cabbage) from Faisalabad, Pakistan, were analyzed for the analysis of heavy metals: cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg). Inductively coupled plasma optical emission spectrometry was used for the analysis of heavy metals. The mean levels of Cd, Pb, As, and Hg were 0.

Synthesis and In Vitro and In Vivo Evaluation of [H]LRRK2-IN-1 as a Novel Radioligand for LRRK2.

Purpose: LRRK2 (leucine-rich repeat kinase 2) has recently been proven to be a promising drug target for Parkinson's disease (PD) due to an apparent enhanced activity caused by mutations associated with familial PD. To date, there have been no reports in which a LRRK2 inhibitor has been radiolabeled and used for in in vitro or in vivo studies of LRRK2. In the present study, we radiolabeled the LRRK2 ligand, LRRK-IN-1, for the purposes of performing in vitro (IC, K , B , autoradiography) and in vivo (biodistribution, and blocking experiments) evaluations in rodents and human striatum tissues.

A Limited Survey of Aflatoxins and Zearalenone in Feed and Feed Ingredients from Pakistan.

This work presents current information on the presence of aflatoxins (AFs) and zearalenone (ZEN) in feed and feed ingredients from Punjab, Pakistan. The 105 samples tested were concentrated feed, i.e.

Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy.

Unlabelled: In peptide receptor radionuclide therapy with (90)Y-labeled DOTATATE, the kidney absorbed dose limits the maximum amount of total activity that can be safely administered in many patients. A higher tumor-to-kidney absorbed dose ratio might be achieved by optimizing the amount of injected peptide and activity, as recent studies have shown different degrees of receptor saturation for normal tissue and tumor. The aim of this work was to develop and implement a modeling method for treatment planning to determine the optimal combination of peptide amount and pertaining therapeutic activity for each patient.

Radiofluorination of PSMA-HBED via Al(18)F(2+) Chelation and Biological Evaluations In Vitro.

Purpose: Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparation, and improved spatial resolution in PET. For F-18 labeling of peptides conjugated with a suitable chelator, a fast and feasible method is the use of [Al(18)F](2+).

Biodistribution and delivery efficiency of unmodified tumor-derived exosomes.

The use of exosomes as a drug delivery vehicle has gained considerable interest. To establish if exosomes could be utilized effectively for drug delivery, a better understanding of their in vivo fate must be established. Through comparisons to liposomal formulations, which have been studied extensively for the last thirty years, we were able to make some comprehensive conclusions about the fate of unmodified tumor-derived exosomes in vivo.

Radiosynthesis of a new PSMA targeting ligand ([18F]FPy-DUPA-Pep).

Due to the specificity of expression of PSMA (prostate specific membrane antigen) particularly in prostate cancer cells (e.g. LNCaP), numerous PSMA ligands have been synthesized until now.