Preclinical evaluation of [F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson's disease: pharmacokinetic and efficacy analysis.

Background: N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). I- and F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [F]FP-CIT as a potential diagnostic biomarker are scarce.

Dosimetric Analysis of a Phase I Study of PSMA-Targeting Radiopharmaceutical Therapy With [Lu]Ludotadipep in Patients With Metastatic Castration-Resistant Prostate Cancer.

Objective: Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC).

Materials And Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [Lu]Ludotadipep (1.

Comparison of the Effects of DOTA and NOTA Chelators on Cu-Cudotadipep and Cu-Cunotadipep for Prostate Cancer.

Background: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, Cu-cudotadipep and Cu-cunotadipep, on pharmacokinetics.

Methods: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

Background: To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients.

Methods: From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia.

Evaluation of PSMA target diagnostic PET tracers for therapeutic monitoring of [Lu]ludotadipep of prostate cancer: Screening of PSMA target efficiency and biodistribution using [F]DCFPyL and [Ga]PSMA-11.

We have compared the similarity of the in vivo distribution of the prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents [F]DCFPyL, [Ga]galdotadipep, and [Ga]PSMA-11. This study is designed for a further selection of a PSMA-targeted PET imaging agent for the therapeutic evaluation of [Lu]ludotadipep, our previously developed prostate-specific membrane antigen (PSMA)-targeted prostate cancer therapeutic radiopharmaceutical. In vitro cell uptake was performed to evaluate the affinity to PSMA using PSMA + PC3-PIP, and PSMA- PC3-flu was used for the study.

Preclinical Evaluation of a Companion Diagnostic Radiopharmaceutical, [F]PSMA-1007, in a Subcutaneous Prostate Cancer Xenograft Mouse Model.

Several radiolabeled prostate-specific membrane antigen (PSMA)-targeted agents have been developed for detecting prostate cancer, using positron emission tomography imaging and targeted radionuclide therapy. Among them, [F]PSMA-1007 has several advantages, including a comparatively long half-life, delayed renal excretion, and compatible structure with α-/β-particle emitter-labeled therapeutics. This study aimed to characterize the preclinical pharmacokinetics and internal radiation dosimetry of [F]PSMA-1007, as well as its repeatability and specificity for target binding using prostate tumor-bearing mice.

A Single Dose of Novel PSMA-Targeting Radiopharmaceutical Agent [Lu]Ludotadipep for Patients with Metastatic Castration-Resistant Prostate Cancer: Phase I Clinical Trial.

[Lu]Ludotadipep, which enables targeted delivery of beta-particle radiation to prostate tumor cells, had been suggested as a promising therapeutic option for mCRPC. From November 2020 to March 2022, a total of 30 patients were enrolled for single dose of [Lu]Ludotadipep RPT, 6 subjects in each of the 5 different activity groups of 1.9 GBq, 2.

Feasibility of Gd-Based prostate cancer targeted magnetic resonance agents using prostate specific membrane antigen.

The aim of this work was to evaluate Gd-FC705, a prostate-specific membrane antigen (PSMA)-targeted MRI contrast agent. The r and r relaxivities of Gd-FC705 are 5.94 mMs and 17.

Improving Theranostic Gallium-68/Lutetium-177-Labeled PSMA Inhibitors with an Albumin Binder for Prostate Cancer.

We developed a novel therapeutic radioligand, [Lu], with an albumin binding motif and evaluated it in a prostate-specific membrane antigen (PSMA)-expressing tumor xenograft mouse model. Fourteen PSMA target candidates were synthesized, and binding affinity was evaluated with an competitive binding assay. First, four compound candidates were selected depending on binding affinity results.

Evaluating N-difluoromethyltriazolium triflate as a precursor for the synthesis of high molar activity [ F]fluoroform.

The trifluoromethyl group is a prominent motif in biologically active compounds and therefore of great interest for the labeling with the positron emitter fluorine-18 for positron emission tomography (PET) imaging. Multiple labeling strategies have been explored in the past; however, most of them suffer from low molar activity due to precursor degradation. In this study, the potential of 1-(difluoromethyl)-3-methyl-4-phenyl-1H-1,2,3-triazol-3-ium triflate as precursor for the synthesis of the [ F]trifluoromethylation building block [ F]fluoroform with high molar activity was investigated.

Automated Synthesis and Initial Evaluation of (4'-Amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-[F]fluorophenyl)methanone for PET/MR Imaging of Inducible Nitric Oxide Synthase.

Background: Inducible nitric oxide synthase (iNOS) plays a crucial role in neuroinflammation, especially microglial activity, and may potentially represent a useful biomarker of neuroinflammation. In this study, we carefully defined a strategic plan to develop iNOS-targeted molecular PET imaging using (4'-amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-fluorophenyl)methanone ([F]FBAT) as a tracer in a mouse model of lipopolysaccharide- (LPS-) induced brain inflammation.

Methods: An model, murine microglial BV2 cell line, was used to assess the uptake of [F]FBAT in response to iNOS induction at the cellular level.

A Phase 0 Microdosing PET/CT Study Using O-[18F]Fluoromethyl-d-Tyrosine in Normal Human Brain and Brain Tumor.

Purpose: The aim of the present study was to obtain information about distribution, radiation dosimetry, toxicity, and pharmacokinetics of O-[18F]fluoromethyl-d-tyrosine (d-18F-FMT), an amino acid PET tracer, in patients with brain tumors.

Patients And Methods: A total of 6 healthy controls (age = 19-25 years, 3 males and 3 females) with brain PET images and radiation dosimetry and 12 patients (median age = 60 years, 6 males and 6 females) with primary (n = 5) or metastatic brain tumor (n = 7) were enrolled. We acquired 60-minute dynamic brain PET images after injecting 370 MBq of d-18F-FMT.

Synthesis of aliphatic α-ketoamides from α-substituted methyl ketones a Cu-catalyzed aerobic oxidative amidation.

α-Ketoamides are an important key functional group and have been used as versatile and valuable intermediates and synthons in a variety of functional group transformations. Synthetic methods for making aryl α-ketoamides as drug candidates have been greatly improved through metal-catalyzed aerobic oxidative amidations. However, the preparation of alkyl α-ketoamides through metal-catalyzed aerobic oxidative amidations has not been reported because generating α-ketoamides from aliphatic ketones with two α-carbons theoretically provides two distinct α-ketoamides.

Mechanistic study of nucleophilic fluorination for the synthesis of fluorine-18 labeled fluoroform with high molar activity from -difluoromethyltriazolium triflate.

The synthesis of fluorine-18 labeled fluoroform with high molar activity has grown in importance for the development of fluorine-18 labeled aryl-CF radiopharmaceuticals that are useful as diagnostic radiotracers for the powerful technique of positron emission tomography (PET). We designed a strategy of synthesizing fluorine-18 labeled fluoroform from 1-difluoromethyl-3-methyltriazolium triflate (1) S2 fluorination without stable fluorine isotope scrambling. Fluoroform was generated at rt in 10 min by fluorination of the triazolium precursor with TBAF (6 equiv.

F-labeled 1,2,3-triazole-linked Glu-urea-Lys-based PSMA ligands have good pharmacokinetic properties for positron emission tomography imaging of prostate cancer.

Background: Prostate-specific membrane antigen (PSMA) is increasingly recognized as an excellent target for prostate cancer imaging and therapy. Finding compounds with a high target-to-nontarget ratio are an important challenge in the development of positron emission tomography (PET) imaging agents. In this study, we attempted to find a suitable compound from a simply-synthesized compound library.

A microdose clinical trial to evaluate [F]Florastamin as a positron emission tomography imaging agent in patients with prostate cancer.

Purpose: To evaluate the biodistribution of [F]Florastamin, a novel F-labelled positron emission tomography (PET) tracer for prostate-specific membrane antigen (PSMA) for the diagnosis of prostate cancer.

Methods: PET was performed for five healthy controls and 10 patients with prostate cancer at 0, 10, 30, 70, and 120 mins after injecting 370 MBq of [F]Florastamin. The maximum standardised uptake value (SUV) was evaluated in the primary tumour.

The correlation of neuropsychological evaluation with 11C-PiB and 18F-FC119S amyloid PET in mild cognitive impairment and Alzheimer disease.

For the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), variable neuroimaging and neuropsychological tests have been used. We aimed to evaluate the correlation of neuropsychological domain with new amyloid positron emission tomography (PET) study and to validate the availability of new PET tracer.We enrolled 20 patients who underwent C-PiB-PET/CT, new PET tracer F-FC119S PET/CT from November, 2014 to July, 2015.

Early Detection of A Deposition in the 5xFAD Mouse by Amyloid PET.

F-FC119S is a positron emission tomography (PET) tracer for imaging -amyloid (A) plaques in Alzheimer's disease (AD). The aim of this study is to evaluate the efficacy of F-FC119S in quantitating A deposition in a mouse model of early amyloid deposition (5xFAD) by PET. .

Head-to-head comparison of F-FP-CIT and I-FP-CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study.

I-FP-CIT and F-FP-CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head-to-head comparisons between I-FP-CIT and F-FP-CIT. Therefore, in this study, I-FP-CIT SPECT/CT was compared with F-FP-CIT PET/CT in the same cohort of subjects.

One-pot radiosynthesis of O-[F]fluoromethyl-D-tyrosine via intra-molecular nucleophilic F-fluorination with 1,2,3-triazolium triflate salt precursor.

A radiolabeled amino acid O-[F]fluoromethyl-D-tyrosine (D-[F]FMT) has been reported to show high tumor uptake. However, introduction of [F]fluoromethyl group was difficult and was an issue to be solved. We solved it by using a precursor containing 1,2,3-triazolium salt.

Preliminary PET Study of F-FC119S in Normal and Alzheimer's Disease Models.

To evaluate the efficacy of F-FC119S as a positron emission tomography (PET) radiopharmaceutical for the imaging of Alzheimer's disease (AD), we studied the drug absorption characteristics and distribution of F-FC119S in normal mice. In addition, we evaluated the specificity of F-FC119S for β-amyloid (Aβ) in the AD group of an APP/PS1 mouse model and compared it with that in the wild-type (WT) group. The behavior of F-FC119S in the normal mice was characteristic of rapid brain uptake and washout patterns.

Head-to-head comparison of 11C-PiB and 18F-FC119S for Aβ imaging in healthy subjects, mild cognitive impairment patients, and Alzheimer's disease patients.

As a new beta amyloid (Aβ) positron emission tomography (PET) tracer, F-FC119S has shown higher cortical uptake in patients with Alzheimer's disease (AD) than that in healthy control subjects without adverse effects in a previous preliminary study. The aim of this study was to compare F-FC119S PET and C-PiB PET in healthy control (HC) subjects, mild cognitive impairment (MCI) patients, and AD patients.A total of 48 subjects, including 28 HC subjects, 10 MCI patients, and 10 AD patients, underwent static F-FC119S PET (30 minutes after intravenous [i.

Hydrogen-bond promoted nucleophilic fluorination: concept, mechanism and applications in positron emission tomography.

Due to the tremendous interest in carbon-fluorine bond-forming reactions, research efforts in this area have been dedicated to the development of facile processes to synthesize small fluorine-containing organic molecules. Among others, PET (Positron Emission Tomography) is one of the most important applications of fluorine chemistry. Recognizing the specific requirements of PET processes, some groups have focused on fluorination reactions using alkali metal fluorides, particularly through SN2-type reactions.

Synthesis and evaluation of 6-(3-[(18)F]fluoro-2-hydroxypropyl)-substituted 2-pyridylbenzothiophenes and 2-pyridylbenzothiazoles as potential PET tracers for imaging Aβ plaques.

3-[(18)F]Fluoro-2-hydroxypropyl substituted compounds were synthesized and evaluated as novel (18)F-labeled PET tracers for imaging Aβ plaque in a living brain. All compounds exhibited high binding affinities toward the synthetic Aβ1-42 aggregate and/or Alzheimer's disease brain homogenate. In the microPET study with normal mice, the 3-[(18)F]fluoro-2-hydroxypropyl substituted compounds resulted in fast brain washout by reducing the lipophilicities of the compounds.