Head to head comparison of two PET/CT imaging agents, [F]D3FSP ([F]P16-129) and [F]AV45, in patients with alzheimer's disease.

Background: A new β-amyloid (Aβ) targeting radiotracer, [F]D3FSP ([F]P16-129), for diagnosis of Alzheimer's disease (AD) is reported. This radiotracer is a deuterated N-methyl derivative of Amyvid (AV-45, florbetapir f18) which was FDA-approved in 2013. Deuteration may alter a tracer's PK such that imaging performance is improved.

Comparison of novel PSMA-targeting [Lu]Lu-P17-087 with its albumin binding derivative [Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study.

Purpose: Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and radioligand therapy (RLT) of prostate cancer. Two novel PSMA-targeting radionuclide therapy agents, [Lu]Lu-P17-087, and its albumin binder modified derivative, [Lu]Lu-P17-088, were evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. The primary endpoint was dosimetry evaluation, the second endpoint was radiation toxicity assessment (CTCAE 5.

Theranostic Agent Targeting Bone Metastasis: A Novel [Ga]Ga/[Lu]Lu-DOTA-HBED-bisphosphonate.

Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [Ga]Ga-HBED-CC-bisphosphonate ([Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or β-emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, ) was prepared and the corresponding [Ga]Ga- and [Lu]Lu- were successfully synthesized in high yields and purity.

First-in-human study of PSMA-targeting agent, [F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

Purpose: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients.

Methods: The [F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled.

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy.

Prostate-specific membrane antigen (PSMA) is an excellent target for imaging and radionuclide therapy of prostate cancer. Recently, [Lu]Lu-PSMA-617 (Pluvicto) was approved by the FDA for radionuclide therapy. To develop hetero-bivalent agents targeting both PSMA and bone metastasis, [Lu]Lu-P17-079 ([Lu]Lu-1) and [Lu]Lu-P17-081 ([Lu]Lu-2) were prepared.

Assessing extra-prostatic extension for surgical guidance in prostate cancer: Comparing two PSMA-PET tracers with the standard-of-care.

Background: Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist.

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177).

Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis and radionuclide therapy of prostate cancer. This study reports conversion of a previously reported Ga-imaging agent, [Ga]Ga-P16-093, to a Lu-177 radionuclide therapeutic agent. Substitution of the HBED-CC metal chelating group with DOTA(GA) led to P17-087 () and P17-088 ().

Preliminary Evaluation of Ga-P16-093, a PET Radiotracer Targeting Prostate-Specific Membrane Antigen in Prostate Cancer.

Purpose: Prostate-specific membrane antigen (PSMA) is a promising molecular target for imaging of prostate adenocarcinoma. Ga-P16-093, a small molecule PSMA ligand, previously showed equivalent diagnostic performance compared to Ga-PSMA-11 PET/CT in a pilot study of prostate cancer patients with biochemical recurrence (BCR). We performed a pilot study for further characterization of Ga-P16-093 including comparison to conventional imaging.

A New Highly Deuterated [F]AV-45, [F]D15FSP, for Imaging β-Amyloid Plaques in the Brain.

[F]AV-45 (florbetapir f18, Amyvid) is an FDA-approved PET imaging agent targeting Aβ plaques in the brain for diagnosis of Alzheimer's disease (AD). Its metabolites led to a high background in the brain and large bone uptake of [F]F, produced from dealkylation of the PEG chain. To slow down the in vivo metabolism, we report the design, synthesis, and evaluation of a highly deuterated derivative, [F]D15FSP, and compared it with -methyl-deuterated [F]D3FSP and nondeuterated [F]AV-45.

Radiolabeling Optimization and Preclinical Evaluation of the New PSMA Imaging Agent [F]AlF-P16-093.

Prostate-specific membrane antigen (PSMA)-targeted radioligands have played an increasing role in the diagnosis of prostate cancer. [Ga]Ga-P16-093 is a PSMA-targeting agent for positron emission tomography imaging, currently under a Phase 2 clinical trial. In the present study, P16-093 was labeled with F via [F]AlF complex formation, and the biological properties of [F]AlF-P16-093 were evaluated.

Synthesis and Evaluation of Ga- and Lu-Labeled ()- vs ()-DOTAGA Prostate-Specific Membrane Antigen-Targeting Derivatives.

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and therefore is an attractive target for prostate cancer diagnosis and radionuclide therapy. Recently, published results from clinical studies using a new PSMA-targeting PET imaging agent, [Ga]Ga-PSMA-093 ([Ga]Ga-HBED-CC--carboxymethyl-Tyr-CO-NH-Glu), support the development of this agent for the diagnosis of prostate cancer. In this study, the HBED-CC chelating group in PSMA-093 was replaced by stereoselective ()- or ()-DOTAGA.

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women.

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women.

Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [Ga]Ga-P15-041, a gallium-68 labeled bisphosphonate, from first-in-human studies.

Introduction: [Ga]Ga-P15-041 ([Ga]Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer that can be generator-produced. We undertook a Phase 0/I clinical trial to assess its potential for imaging bone metastases in prostate cancer including assessment of radiotracer biodistribution and dosimetry.

Methods: Subjects with prostate cancer and known or suspected osseous metastatic disease were enrolled into one of two arms: dosimetry or dynamic.

A New [Ga]Ga-HBED-CC-Bisphosphonate as a Bone Imaging Agent.

Positron emission tomography (PET) imaging using Ga-labeled bisphosphonates to target bone metastasis could be a valuable tool in cancer diagnosis and monitoring therapeutic treatment. A Ga labeled ligand, ,-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-,-diacetic acid (HBED-CC) containing one bisphosphonate group (HBED-CC-BP, ) was prepared and evaluated. The new ligand, , reacted rapidly to form [Ga]Ga-, via complexing with [Ga]GaCl eluted from a commercially available Ge/Ga generator (in a sodium acetate buffer at pH 4, reaching >95% labeling yield at room temperature in 5 min).

Preclinical evaluation of [F]D3FSP, deuterated AV-45, for imaging of β-amyloid in the brain.

Introduction: Since the approval of three F labeled β-amyloid-targeting PET imaging agents, Amyvid (florbetapir f18, AV-45), Neuraceq (florbetaben f18, AV-1) and Vizamyl (flutemetamol f18, F-PIB), they have increasingly been employed to assist differential diagnosis of Alzheimer's disease in patients with dementia. Also, they are frequently used in selecting patients participating drug trials aiming to reduce β-amyloid (Aβ) plaques in the brain. The first approved tracer in this class was [F]AV-45, which is metabolized rapidly in blood and some of its N-demethylated metabolites cross the blood brain barrier and resulted in lowering the image contrast.

Synthesis and evaluation of novel radioiodinated PSMA targeting ligands for potential radiotherapy of prostate cancer.

Radioligand therapy (RLT) using prostate-specific membrane antigen (PSMA) targeting ligands is an attractive option for the treatment of Prostate cancer (PCa) and its metastases. We report herein a series of radioiodinated glutamate-urea-lysine-phenylalanine derivatives as new PSMA ligands in which l-tyrosine and l-glutamic acid moieties were added to increase hydrophilicity concomitant with improvement of in vivo targeting properties. Compounds 8, 15, 19a/19b and 23a/23b were synthesized and radiolabeled with I by iododestannylation.

[Ga]Ga-P16-093 as a PSMA-Targeted PET Radiopharmaceutical for Detection of Cancer: Initial Evaluation and Comparison with [Ga]Ga-PSMA-11 in Prostate Cancer Patients Presenting with Biochemical Recurrence.

Purpose: This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence.

Procedures: Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care.

Synthesis of l-[4- C]Asparagine by Ring-Opening Nucleophilic C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor.

The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains a challenge. This is especially true for the synthesis of carbon-11-labeled AAs given the short half-life of carbon-11 ( C, t =20.4 min).

A mild, rapid synthesis of freebase [C]nicotine from [C]methyl triflate.

A rapid, mild radiosynthesis of freebase [C]nicotine was developed by the methylation of freebase nornicotine with [C]methyl triflate in acetone (5min, 45°C). A basic (pH 10.5-11.

In vivo quantitative imaging of photoassimilate transport dynamics and allocation in large plants using a commercial positron emission tomography (PET) scanner.

Background: Although important aspects of whole-plant carbon allocation in crop plants (e.g., to grain) occur late in development when the plants are large, techniques to study carbon transport and allocation processes have not been adapted for large plants.