Novel [Ga/Lu]Ga/Lu-AZ-093 as PSMA-Targeting Agent for Diagnosis and Radiotherapy.

Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer cells can serve as a target for imaging and radioligand therapy (RLT). Previously, [Ga]Ga-P16-093, containing a Ga(III) chelator, ,'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-,'-diacetic acid (HBED-CC), displayed excellent PSMA-targeting properties and showed a high tumor uptake and retention useful for diagnosis in prostate cancer patients. Recently, [Lu]Lu-PSMA-617 has been approved by the U.

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.

[Ga]Ga-HBED-CC-FAPI Derivatives with Improved Radiolabeling and Specific Tumor Uptake.

Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher stability constant (log: 38.

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 ().

Kit-based preparation of [Ga]Ga-P16-093 (PSMA-093) using different commercial Ge/Ga generators.

Purpose: Prostate-specific membrane antigen (PSMA) is an important biomarker for molecular imaging and a target for radionuclide therapy of prostate cancer. Recently, U.S.

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.

Development and validation of a kit formulation of [Ga]Ga-P15-041 as a bone imaging agent.

One of the commonly performed studies in nuclear medicine are bone scans with [Tc]Tc-methylene diphosphonate (MDP) for detecting various bone lesions, including cancer metastasis. The recent emergence of commercially available Ge/Ga radionuclide generators makes it possible to provide Ga-labelled bisphosphonates as positron emission tomography (PET) tracers for bone imaging. Preliminary human studies suggested that [Ga]Ga-HBED-CC-BP ([Ga]Ga-P15-041) in conjunction with PET/computed tomography (CT) showed accumulation in known bone lesions, fast clearance from blood and soft tissue, and an ability to provide high contrast images.

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.

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.

VMAT2 imaging agent, D6-[F]FP-(+)-DTBZ: Improved radiosynthesis, purification by solid-phase extraction and characterization.

Objectives: Recently, a deuterated tracer, D6-[F]FP-(+)-DTBZ, 9-O-hexadeutero-3-[F]fluoropropoxyl-(+)-dihydrotetrabenazine ([F]9), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system, was reported as a useful imaging agent for the diagnosis of Parkinson's disease (PD). The production of [F]9 was optimized and simplified by using solid-phase extraction (SPE) purification.

Methods: Three major nonradioactive impurities were synthesized and characterized.

Optimization of solid-phase extraction (SPE) in the preparation of [F]D3FSP: A new PET imaging agent for mapping Aβ plaques.

Introduction: Alzheimer's disease is a common neurodegenerative disease that is characterized by the presence of Aβ plaques in the brain. The FDA has approved the use of Amyvid (florbetapir f18, AV-45) as a PET imaging agent for detecting Aβ plaques in the living human brain. In an attempt to reduce N-demethylation in vivo by taking advantage of more stable C-D bonds, an analog of AV-45, [F]D3FSP ([F]7), was synthesized to improve image contrast for detecting and monitoring the Aβ plaques.

Initial experience in synthesis of (2S,4R)-4-[ F]fluoroglutamine for clinical application.

We report initial experience in synthesis of (2S,4R)-4-[ F]fluoroglutamine, [ F]FGln, which has been used as a tool for monitoring glutamine metabolism in cancer patients. [ F]FGln was prepared by a fully automated PET-MF-2V-IT-I synthesizer under GMP-compliant conditions for routine clinical studies. The total radiosynthesis time was about 65 minutes, the decay-corrected radiochemical yield was 18.

Fluorine-18 labeled diphenyl sulfide derivatives for imaging serotonin transporter (SERT) in the brain.

Objectives: Serotonin transporters (SERT) play an important role in controlling serotonin concentration in the synaptic cleft and in managing postsynaptic signal transduction. Inhibitors of SERT binding are well known as selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, and escitalopram, that are commonly prescribed antidepressants. Positron emission tomography (PET) and single photon emission tomography (SPECT) imaging agents targeting SERT may be useful for studying its function and providing a tool for monitoring drug treatment.

Alanine and glycine conjugates of (2S,4R)-4-[F]fluoroglutamine for tumor imaging.

Introduction: Glutamine is an essential source of energy, metabolic substrates, and building block for supporting tumor proliferation. Previously, (2S,4R)-4-[F]fluoroglutamine (4F-Gln) was reported as a glutamine-related metabolic imaging agent. To improve the in vivo kinetics of this radiotracer, two new dipeptides, [F]Gly-(2S,4R)4-fluoroglutamine (Gly-4F-Gln) and [F]Ala-(2S,4R)4-fluoroglutamine (Ala-4F-Gln) were investigated.

Synthesis and evaluation of a novel urea-based Ga-complex for imaging PSMA binding in tumor.

Introduction: Prostate specific membrane antigen (PSMA) is a well-established target for diagnostic and therapeutic applications for prostate cancer. It is know that [Ga]PSMA 11 ([Ga]Glu-NH-CO-NH-Lys(Ahx)-HBED-CC) is the most well studied PET imaging agent for detecting over expressed PSMA binding sites of tumors in humans. In an effort to provide new agents with improved characteristics for PET imaging, we report a novel [Ga]-Glu-NH-CO-NH-Lys(Ahx)-linker-HBED-CC conjugate with a novel O-(carboxymethyl)-L-tyrosine, as the linker group.