Biodistribution of a Mitochondrial Metabolic Tracer, [F]F-AraG, in Healthy Volunteers.

Purpose: [F]F-AraG is a radiolabeled nucleoside analog that shows relative specificity for activated T cells. The aim of this study was to investigate the biodistribution of [F]F-AraG in healthy volunteers and assess the preliminary safety and radiation dosimetry.

Methods: Six healthy subjects (three female and three male) between the ages of 24 and 60 participated in the study.

Intraarterial Peptide Receptor Radionuclide Therapy Using Y-DOTATOC for Hepatic Metastases of Neuroendocrine Tumors.

Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from intravenous administration as previously reported in the literature. PRRT-naïve adult neuroendocrine tumor patients with liver-dominant metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous Ga-DOTATOC.

Sensing Living Bacteria Using d-Alanine-Derived C Radiotracers.

Incorporation of d-amino acids into peptidoglycan is a unique metabolic feature of bacteria. Since d-amino acids are not metabolic substrates in most mammalian tissues, this difference can be exploited to detect living bacteria . Given the prevalence of d-alanine in peptidoglycan muropeptides, as well as its role in several antibiotic mechanisms, we targeted this amino acid for positron emission tomography (PET) radiotracer development.

High Enantiomeric Excess In-Loop Synthesis of d-[methyl-C]Methionine for Use as a Diagnostic Positron Emission Tomography Radiotracer in Bacterial Infection.

Currently, there exists no accurate, noninvasive clinical imaging method to detect living bacteria . Our goal is to provide a positron emission tomography (PET) method to image infection by targeting bacteria-specific metabolism. Standard of care methodologies detect morphologic changes, image immunologic response to infection, or employ invasive tissue sampling with associated patient morbidity.

Imaging of Activated T Cells as an Early Predictor of Immune Response to Anti-PD-1 Therapy.

Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. In this study, we evaluate a T-cell-specific PET agent, [18F]F-AraG, as an imaging biomarker predictive of response to checkpoint inhibitor therapy.

Quantitative and Qualitative Improvement of Low-Count [Ga]Citrate and [Y]Microspheres PET Image Reconstructions Using Block Sequential Regularized Expectation Maximization Algorithm.

Purpose: There are several important positron emission tomography (PET) imaging scenarios that require imaging with very low photon statistics, for which both quantitative accuracy and visual quality should not be neglected. For example, PET imaging with the low photon statistics is closely related to active efforts to significantly reduce radiation exposure from radiopharmaceuticals. We investigated two examples of low-count PET imaging: (a) imaging [Y]microsphere radioembolization that suffers the very small positron emission fraction of Y-90's decay processes, and (b) cancer imaging with [Ga]citrate with uptake time of 3-4 half-lives, necessary for visualizing tumors.

Phase I Study of CTT1057, an F-Labeled Imaging Agent with Phosphoramidate Core Targeting Prostate-Specific Membrane Antigen in Prostate Cancer.

Agents targeting prostate-specific membrane antigen (PSMA) comprise a rapidly emerging class of radiopharmaceuticals for diagnostic imaging of prostate cancer. Unlike most other PSMA agents with a urea backbone, CTT1057 is based on a phosphoramidate scaffold that irreversibly binds to PSMA. We conducted a first-in-humans phase I study of CTT1057 in patients with localized and metastatic prostate cancer.

In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis.

Background: Evolving immune-mediated therapeutic strategies for rheumatoid arthritis (RA) may benefit from an improved understanding of the complex role that T-cell activation plays in RA. This study assessed the potential of fluorine-18-labeled 9-β-d-arabinofuranosylguanine ([F]F-AraG) positron emission tomography (PET) imaging to report immune activation in vivo in an adjuvant-induced arthritis (AIA) small animal model.

Methods: Using positron emission tomography-computed tomography imaging, uptake of [F]F-AraG in the paws of mice affected by arthritis at 6 (acute) and 20 (chronic) days following AIA induction in a single paw was assessed and compared to uptake in contralateral control paws.

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages.

Structure-Activity Relationship of (18)F-Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer.

A series of phosphoramidate-based prostate specific membrane antigen (PSMA) inhibitors of increasing lipophilicity were synthesized (4, 5, and 6), and their fluorine-18 analogs were evaluated for use as positron emission tomography (PET) imaging agents for prostate cancer. To gain insight into their modes of binding, they were also cocrystallized with the extracellular domain of PSMA. All analogs exhibited irreversible binding to PSMA with IC50 values ranging from 0.

A high-affinity [(18)F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer.

Introduction: In this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated.

Methods: p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex.

Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor.

Objective: To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent.

Materials And Methods: Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging.

In vivo dopamine transporter imaging in a unilateral 6-hydroxydopamine rat model of Parkinson disease using 11C-methylphenidate PET.

Unlabelled: Dopamine transporter (DAT) function is altered by many neurodegenerative diseases. For instance, in Parkinson disease DAT density has been shown to decrease in early disease and to play a role in the occurrence of motor complications. DAT is thus an important imaging target with potential therapeutic relevance in humans and animal models of disease.

Antiparkinsonian mechanism of electroconvulsive therapy in MPTP-lesioned non-human primates.

Background: Electroconvulsive therapy (ECT), an effective treatment for depression, also improves motor symptomatology in Parkinson's disease (PD). We have previously demonstrated that ECT stimulates dopamine (DA) function in the striatum of healthy non-human primates, suggesting that DA may contribute to antidepressant effects.

Objective: We investigated the potential role of DA mechanisms in the amelioration of PD symptoms following a clinical course of ECT.

Effect of age on markers for monoaminergic neurons of normal and MPTP-lesioned rhesus monkeys: a multi-tracer PET study.

The binding of three tracers for monoaminergic terminals was mapped in the brain of healthy young (N=6) and healthy old rhesus monkeys (N=4), aged monkeys with mild unilateral intracarotid MPTP lesions (N=3), and monkeys of intermediate age with severe systemic MPTP lesions (N=6). The ligand for monoaminergic vesicles (+)-[(11)C]dihydrotetrabenazine (+DTBZ) had a mean binding potential (pB) of 1.4 in striatum of the healthy young monkeys, which was reduced by 20% in putamen of the old monkeys.

Quantitative in vitro phosphor imaging using [3H] and [18F] radioligands: the effects of chronic desipramine treatment on serotonin 5-HT2 receptors.

Traditionally, autoradiography of neuroreceptors is performed in vitro using tritiated ligands and low sensitivity X-ray film, requiring long exposure times. In vivo imaging of neuroreceptors using positron emission tomography (PET) suffers poor spatial resolution, but in vitro PET autoradiography is difficult with film due to the short half-life of the isotopes. Storage phosphor screens provide an extremely sensitive alternative to film.

Studies of the mechanism of the in-loop synthesis of radiopharmaceuticals.

A series of experiments were performed to better understand the mechanism of the In-loop [11C]CH3I-methylation. The timing of [11C]CH3I delivery is critical for the high yield of radiolabeling since in-loop radioactivity trapping is reversible. Trapped radioactivity escapes faster from a Tefzel loop compared to a PEEK- or stainless steel loop.

Improved yields for the in situ production of [11C]CH4 using a niobium target chamber.

The in situ production of [11C]CH4 using a niobium metal target chamber is described. Improved yields are observed in comparison to the previously reported aluminum conical target under similar conditions of beam energy and current. An empirical expression is proposed that quantifies the loss of yield as a function of irradiation time.

In vivo measurement of receptor density and affinity: comparison of the routine sequential method with a nonsequential method in studies of dopamine D2 receptors with [11C]raclopride.

Positron emission tomography with the dopamine D(2/3) receptor ligand raclopride was used to compare sequential (studies on 1 day) and nonsequential (different days) approaches to in vivo measurement of the density and affinity of receptors. The choice of temporal sequence of radiotracer injection over a range of specific activities might result in bias because of diverse factors. A strong concordance is reported between the outcomes of the sequential and nonsequential methods.

In vivo receptor assay with multiple ligand concentrations: an equilibrium approach.

The ligand-receptor binding potential determined by PET studies at high ligand-specific radioactivity reflects both the receptor density and ligand-receptor affinity. This ambiguity has been resolved by various methods based on the administration of multiple unlabeled ligand concentrations. The authors aimed to implement and refine an approach to multiple ligand concentration receptor assay that combined maximum simplicity and a minimum of assumptions and model dependence that would nonetheless reliably distinguish density from affinity effects.