Radiofluorination of PSMA-HBED via Al18F2+ Chelation and Biological Evaluations In Vitro

  title={Radiofluorination of PSMA-HBED via Al18F2+ Chelation and Biological Evaluations In Vitro},
  author={Noeen Malik and Benjamin Baur and Gordon Winter and Sven Norbert Reske and Ambros J Beer and Christoph Solbach},
  journal={Molecular Imaging and Biology},
PurposeGa-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparation, and improved spatial resolution in PET. For F-18 labeling of peptides conjugated with a suitable chelator, a fast and feasible method is the use of [Al18F]2+. In the present… 

PSMA Ligands for Imaging Prostate Cancer: Alternative Labeling by Complex Formation with Al18F2+

In case of prostate cancer (PCa), Prostate Specific Membrane Antigen (PSMA) is shown to be a very valuable target for application by various ligands in clinical diagnosis and there are various compounds labeled with gallium-68 and fluorine-18.

Synthesis and preclinical evaluation of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand

18F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios and the kidneys were the dose-limiting organs.

Validation of a [Al18F]PSMA-11 preparation for clinical applications.

  • E. Al-MomaniI. IsraelS. Samnick
  • Biology
    Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine
  • 2017

Radiolabeling Optimization and Preclinical Evaluation of the New PSMA Imaging Agent [18F]AlF-P16-093.

18F]AlF-P16-093 showed desirable in vivo pharmacokinetics and excellent PSMA-targeting properties for imaging PSMA expression in prostate cancer.

Recent advancements in 18F-labeled PSMA targeting PET radiopharmaceuticals.

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

The proposed method allowed the production of [18F]AlF-PSMA with suitable radiochemical purity in a commercial platform and high activities were achieved, with a simple and robust methodology appropriate for clinical purposes.

One-Step 18F-Labeling and Preclinical Evaluation of Prostate-Specific Membrane Antigen Trifluoroborate Probes for Cancer Imaging

PSMA-targeting probes with trifluoroborate prosthetic groups represent promising candidates for prostate cancer imaging because of facile labeling while affording high tumor uptake values and contrast ratios that are similar to those obtained with 18F-DCFPyL.

Enzymatic radiosynthesis of a 18F-Glu-Ureido-Lys ligand for the prostate-specific membrane antigen (PSMA).

A new fluorinated PSMA targeting small-molecule, FDA-PEG-GUL, which possesses the Glu-NH-CO- NH-Lys pharmacophore conjugated to a 5'-fluorodeoxy-adenosine unit is reported herein, establishing a successful substrate scope expansion for the fluorinase and demonstrates its first application towards targeting the PSMA.

Automated synthesis of [18F]DCFPyL via direct radiofluorination and validation in preclinical prostate cancer models

An automated synthesis of [18F]DCFPyL via direct radiofluorination and validation in preclinical models of prostate cancer confirmed high PSMA-mediated tumor uptake combined with superior clearance parameters and points to a two-step molecular trapping mechanism based on PSMA binding and subsequent internalization leading to retention of radioactivity in PSMA+ LNCaP tumors.

Fluorine-18 Labeled Urea-Based Ligands Targeting Prostate-Specific Membrane Antigen (PSMA) with Increased Tumor and Decreased Renal Uptake

The most lipophilic tracer, [18F]2a, displayed comparable tumor-targeting to [ 18F]DCFPyL and a desirable alteration in pharmacokinetics and metabolism, resulting in significantly lower kidney uptake with a shift towards hepatobiliary clearance and increased liver uptake.



Radiofluorination using aluminum-fluoride (Al18F)

Because fluorine binds to aluminum, a procedure where the Al18F complex could be captured by a chelate, thereby greatly simplifying the way that imaging agents can be fluorinated for PET imaging is developed.

Tetrafluorophenolate of HBED-CC: a versatile conjugation agent for 68Ga-labeled small recombinant antibodies

The coupling of about one HBED-CC per antibody proved to be sufficient for efficient 68Ga labeling, pointing to the successful application of 68Ga for molecular imaging with small recombinant proteins.

Comment on Afshar-Oromieh et al.: PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions

In a study comprising 37 patients a discussion of 42 patients in the text needs clarification, the assumption that a prostate involved with prostate cancer and treated with local radiation therapy and androgen deprivation therapy can be regarded as a ‘normal prostate’ is not followed.

One pot radiofluorination of a new potential PSMA ligand [Al18F]NOTA‐DUPA‐Pep

Up to now, many radiolabeled ligands targeting prostate-specific membrane antigen (PSMA) have been synthesized. To carry out radiofluorinations, there have been several approaches mainly involving

A Novel Facile Method of Labeling Octreotide with 18F-Fluorine

NotA-octreotide could be labeled rapidly and efficiently with 18F using a 2-step, 1-pot method and was stable in vivo and showed rapid accretion in somatostatin receptor subtype 2–expressing AR42J tumors in nude mice.

First Experience of 18F-Alfatide in Lung Cancer Patients Using a New Lyophilized Kit for Rapid Radiofluorination

A simple lyophilized kit for labeling PRGD2 peptide (18F-AlF-NOTA-PRGD2, denoted as 18F-alfatide) using a fluoride–aluminum complex that significantly simplified the labeling procedure is developed and can be produced with excellent radiochemical yield and purity via a simple, 1-step, lyophile kit.

PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions

The biodistribution of the novel 68Ga-PSMA tracer and its ability to detect PC lesions was analysed in 37 patients to suggest that this novel tracer can detect PC relapses and metastases with high contrast.

Design, synthesis, and preclinical evaluation of prostate-specific membrane antigen targeted (99m)Tc-radioimaging agents.

Collectively, these high affinity, PSMA-specific radioimaging agents demonstrate significant potential for use in localizing prostate cancer masses, monitoring response to therapy, detecting prostate cancer recurrence following surgery, and selecting patients for subsequent PSma-targeted chemotherapy.

New lyophilized kit for rapid radiofluorination of peptides.

It is indicated that (18)F-labeled peptides can be reproducibly prepared as stable Al-F complexes with good radiochemical yield and high specific activity using a simple, one-step, lyophilized kit followed by a rapid purification by SPE that provides the (18]F-peptide ready for patient injection within 30 min.

Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex.

Several new NOTA ligands were examined and stable Al(18)F NOTA complexes were stable in vitro in human serum, and those that were tested in vivo also were stable.