Reproducibility and repeatability of 18F-(2S, 4R)-4-fluoroglutamine PET imaging in preclinical oncology models.

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task.

Biological Evaluation of d-[F]Fluoroalanine and d-[F]Fluoroalanine- as Positron Emission Tomography Imaging Tracers for Bacterial Infection.

d-Amino acids such as d-alanine are substrates for bacterial peptidoglycan biosynthesis and are selectively taken up by bacteria and not mammalian cells. Consequently, d-amino acid metabolism is an attractive target for antibiotic discovery and the development of bacteria-specific imaging agents. d-Fluoroalanine and the deuterium-labeled analogue fludalanine (MK641) were originally explored as antibiotics by Merck but failed in clinical trials due to unaccepted toxicity.

Synthesis and Biological Evaluation of Fluorine-18 and Deuterium Labeled l-Fluoroalanines as Positron Emission Tomography Imaging Agents for Cancer Detection.

To fully explore the potential of F-labeled l-fluoroalanine for imaging cancer and other chronic diseases, a simple and mild radiosynthesis method has been established to produce optically pure l-3-[F]fluoroalanine (l-[F]FAla), using a serine-derivatized, five-membered-ring sulfamidate as the radiofluorination precursor. A deuterated analogue, l-3-[F]fluoroalanine-d (l-[F]FAla-d), was also prepared to improve metabolic stability. Both l-[F]FAla and l-[F]FAla-d were rapidly taken up by 9L/lacZ, MIA PaCa-2, and U87MG cells and were shown to be substrates for the alanine-serine-cysteine (ASC) amino acid transporter.

Evaluating the Impact of the Tyr158 p on the Mechanism and Inhibition of InhA, the Enoyl-ACP Reductase from .

InhA, the enoyl-ACP reductase, is a target for the tuberculosis (TB) drug isoniazid (INH). InhA inhibitors that do not require KatG activation avoid the most common mechanism of INH resistance, and there are continuing efforts to fully elucidate the enzyme mechanism to drive inhibitor discovery. InhA is a member of the short-chain dehydrogenase/reductase superfamily characterized by a conserved active site Tyr, Y158 in InhA.

Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase.

Bruton's tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases. To aid in the discovery and development of BTK inhibitors and improve clinical diagnoses, we have developed a positron emission tomography (PET) radiotracer based on a selective BTK inhibitor, remibrutinib. [F]PTBTK3 is an aromatic, F-labeled tracer that was synthesized in 3 steps with a 14.

Evaluations of the performances of PET and MRI in a simultaneous PET/MRI instrument for pre-clinical imaging.

Background: PET/MRI is an attractive imaging modality due to the complementary nature of MRI and PET. Obtaining high quality small animal PET/MRI results is key for the translation of novel PET/MRI agents and techniques to the radiology clinic. To obtain high quality imaging results, a hybrid PET/MRI system requires additional considerations beyond the standard issues with separate PET and MRI systems.

PET/MR Imaging of a Lung Metastasis Model of Clear Cell Renal Cell Carcinoma with (2S,4R)-4-[F]Fluoroglutamine.

Purpose: Metabolic reprogramming plays an important role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Currently, positron emission tomography (PET) reporters are not used clinically to visualize altered glutamine metabolism in ccRCC, which greatly hinders detection, staging, and real-time therapeutic assessment. We sought to determine if (2S,4R)-4-[F]fluoroglutamine ([F]FGln) could be used to interrogate altered glutamine metabolism in ccRCC lesions in the lung.

Radiometal-Based PET/MRI Contrast Agents for Sensing Tumor Extracellular pH.

Acidosis is a useful biomarker for tumor diagnoses and for evaluating early response to anti-cancer treatments. Despite these useful applications, there are few methods for non-invasively measuring tumor extracellular pH, and none are routinely used in clinics. Responsive MRI contrast agents have been developed, and they undergo a change in MRI signal with pH.

Simultaneous Evaluations of pH and Enzyme Activity with a CEST MRI Contrast Agent.

The extracellular tumor microenvironment of many solid tumors has high acidosis and high protease activity. Simultaneously assessing both characteristics may improve diagnostic evaluations of aggressive tumors and the effects of anticancer treatments. Noninvasive imaging methods have previously been developed that measure extracellular pH or can detect enzyme activity using chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI).

Evaluation of the Biodistribution of Serinolamide-Derivatized C Fullerene.

Carbon nanoparticles have consistently been of great interest in medicine. However, there are currently no clinical materials based on carbon nanoparticles, due to inconsistent biodistribution and excretion data. In this work, we have synthesized a novel C derivative with a metal chelating agent (1,4,7-Triazacyclononane-1,4,7-triacetic acid; NOTA) covalently bound to the C cage and radiolabeled with copper-64 (t = 12.

Summary of Imaging in 2020: Visualizing the Future of Healthcare with MR Imaging.

The Imaging in 2020 meeting convenes biannually to discuss innovations in medical imaging. The 2018 meeting, titled "Visualizing the Future of Healthcare with MR Imaging," sought to encourage discussions of the future goals of MRI research, feature important discoveries, and foster scientific discourse between scientists from a variety of fields of expertise. Here, we highlight presented research and resulting discussions of the meeting.

Clinical applications of chemical exchange saturation transfer (CEST) MRI.

Unlabelled: Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has been developed and employed in multiple clinical imaging research centers worldwide. Selective radiofrequency (RF) saturation pulses with standard 2D and 3D MRI acquisition schemes are now routinely performed, and CEST MRI can produce semiquantitative results using magnetization transfer ratio asymmetry (MTR ) analysis while accounting for B inhomogeneity. Faster clinical CEST MRI acquisition methods and more quantitative acquisition and analysis routines are under development.