Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice.

This study evaluates the efficacy of [I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation.

From Bench to Bedside: Patient-Oriented Radiopharmaceutical Development in Nuclear Medicine Based on the Example of [Zr]Zr-PSMA-DFO.

The interdisciplinary possibilities inherent in nuclear medicine offer an opportunity for the patient-centered development of radioactive pharmaceuticals based on specific research questions. This approach provides radiopharmaceutical manufacturers with a robust scientific foundation on which to navigate the regulatory requirements for drug approval laid down by the law. A vivid illustration of this interdisciplinary cooperation has been the development of a Zr-89-labeled PSMA ligand where reliable results have been obtained across various domains, including chemistry, radiochemistry, biochemistry, and preclinical research.

Threshold for defining PSMA-positivity prior to Lu-PSMA therapy: a comparison of [Ga]Ga-PSMA-11 and [F]F-DCFPyL in metastatic prostate cancer.

Background: In 2022, the American Food and Drug Administration and the European Medicines Agency approved [Lu]Lu-PSMA-617 (PLUVICTO™, Novartis AG, Basel, Switzerland) for radionuclide therapy with prostate-specific membrane antigen (PSMA) ligands in metastatic prostate cancer. Theranostics require appropriate patients to be identified by positron emission tomography (PET) prior to radionuclide therapy, usually employing [Ga]Ga-PSMA-11. Alternatively, several F-labelled PSMA-PET tracers are available and may increasingly replace Ga-labelled compounds, with respect to their image quality, availability and other practical advantages.

Assessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study.

Cerebral glucose hypometabolism is a typical hallmark of Alzheimer's disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [F]PI-2620 for tau deposition, [F]DPA-714 for TSPO expression associated with neuroinflammation, and [F]UCB-H for synaptic density in a transgenic tauopathy mouse model.

F-Labeled magnetic nanovectors for bimodal cellular imaging.

Surface modification of nanocarriers enables selective attachment to specific molecular targets within a complex biological environment. Besides the enhanced uptake due to specific interactions, the surface ligands can be utilized for radiolabeling applications for bimodal imaging ensured by positron emission topography (PET) and magnetic resonance imaging (MRI) functions in one source. Herein, we describe the surface functionalization of magnetite (FeO) with folic acid as a target vector.

[F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer.

Purpose: PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [F]-JK-PSMA-7 under ADT.

Intraindividual Comparison of F-PSMA-1007 with Renally Excreted PSMA Ligands for PSMA PET Imaging in Patients with Relapsed Prostate Cancer.

F-prostate-specific membrane antigen (PSMA)-1007 is excreted mainly through the liver. We benchmarked the performance of F-PSMA-1007 against 3 renally excreted PSMA tracers. Among 668 patients, we selected 27 in whom PET/CT results obtained with Ga-PSMA-11, F-DCFPyL (2-(3-(1-carboxy-5-[(6-[F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid), or F-JK-PSMA-7 (JK, Juelich-Koeln) were interpreted as equivocal or negative or as oligometastatic disease (PET-1).

Biodistribution and radiation dosimetry of [F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer.

Aim: We investigated the whole-body distribution and the radiation dosimetry of [F]-JK-PSMA-7, a novel F-labeled PSMA-ligand for PET/CT imaging of prostate cancer.

Methods: Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329-384 MBq (mean 359 ± 17 MBq) [F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval.

An F-Labeled PSMA Ligand for PET/CT of Prostate Cancer: First-in-Humans Observational Study and Clinical Experience with F-JK-PSMA-7 During the First Year of Application.

In preclinical trials, the recently developed tracer 2-methoxy-F-DCFPyL (F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. In an Institutional Review Board-approved pilot study, the initial clinical utility of PET/CT imaging with F-JK-PSMA-7 was directly compared with Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer.

Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents.

Background: The recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy.

Methods: We explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes.

Minimalist approach meets green chemistry: Synthesis of F- labeled (hetero)aromatics in pure ethanol.

The application of toxic solvents and additives is inevitable for most of the described protocols for F-labeling. Herein, a novel "green" procedure for nucleophilic aromatic radiofluorination of highly activated (hetero)aromatic substrates in pure EtOH is described. Using this method a series of F-labeled (hetero)arenes have been synthesized in radiochemical yields (RCYs) of up to 97%.

Uptake in non-affected bone tissue does not differ between [18F]-DCFPyL and [68Ga]-HBED-CC PSMA PET/CT.

Introduction: [68Ga]PSMA-HBED-CC and [18F]DCFPyL show a high potential for the detection of recurrent prostate cancer. While 18F-based tracers have several advantages in availability and image resolution, their sensitivity in the skeleton might be impaired by released [18F]fluoride due to its high bone affinity. In turn, chemically unbound trivalent 68Ga might also accumulate in osseous tissue, in cases of occupied binding sites of plasma proteins and thereby influence bone signal.

Discovery of F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions.

Prostate-specific membrane antigen (PSMA), expressed by most prostate carcinomas (PCa), is a promising target for PCa imaging. The application of PSMA-specific F-labeled PET probes such as F-DCFPyL and F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements in sensitivity and specificity.

In vivo Molecular Imaging of Glutamate Carboxypeptidase II Expression in Re-endothelialisation after Percutaneous Balloon Denudation in a Rat Model.

The short- and long-term success of intravascular stents depends on a proper re-endothelialisation after the intervention-induced endothelial denudation. The aim of this study was to evaluate the potential of in vivo molecular imaging of glutamate carboxypeptidase II (GCPII; identical with prostate-specific membrane antigen PSMA) expression as a marker of re-endothelialisation. Fifteen Sprague Dawley rats underwent unilateral balloon angioplasty of the common carotid artery (CCA).

A Practical Method for the Preparation of F-Labeled Aromatic Amino Acids from Nucleophilic [F]Fluoride and Stannyl Precursors for Electrophilic Radiohalogenation.

In a recent contribution of Scott et al., the substrate scope of Cu-mediated nucleophilic radiofluorination with [F]KF for the preparation of F-labeled arenes was extended to aryl- and vinylstannanes. Based on these findings, the potential of this reaction for the production of clinically relevant positron emission tomography (PET) tracers was investigated.

Automated synthesis of 4-[(18)F]fluoroanisole, [(18)F]DAA1106 and 4-[(18)F]FPhe using Cu-mediated radiofluorination under "minimalist" conditions.

The application of the "minimalist" approach to Cu-mediated radiofluorination allows the efficient preparation of (18)F-labeled arenes regardless of their electronic properties. The implementation of this methodology on a commercially available synthesis module (hotbox(three), Scintomics, Germany) enabled the automated production of 4-[(18)F]fluoroanisole as well as the clinically relevant PET-tracers, 4-[(18)F]FPhe and [(18)F]DAA1106, in radiochemical yields of 41-61% and radiochemical purities of >95% within 30-60min. These results demonstrated the high efficacy and versatility of the developed method that will open up opportunities for a broad application of Cu-mediated radiofluorination in PET-chemistry.

Comparison of [(18)F]DCFPyL and [ (68)Ga]Ga-PSMA-HBED-CC for PSMA-PET Imaging in Patients with Relapsed Prostate Cancer.

Purpose: Gallium-68 (Ga-68)-labeled tracers for imaging expression of the prostate-specific membrane antigen (PSMA) such as the [(68)Ga]Ga-PSMA-HBED-CC have already demonstrated high potential for the detection of recurrent prostate cancer. However, compared to Ga-68, a labeling with fluorine-18 (F-18) would offer advantages with respect to availability, production amount, and image resolution. [(18)F]DCFPyL is a promising F-18-labeled candidate for PSMA-positron emission tomography (PET) imaging that has been recently introduced.

Copper-mediated aromatic radiofluorination revisited: efficient production of PET tracers on a preparative scale.

Two novel methods for copper-mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small-scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a "low base" protocol has been developed which affords (18)F-labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields.

Synthesis of ¹⁸F-labelled β-lactams by using the Kinugasa reaction.

Owing to their broad spectrum of biological activities and low toxicity, β-lactams are attractive lead structures for the design of novel molecular probes. However, the synthesis of positron emission tomography (PET)-isotope-labelled β-lactams has not yet been reported. Herein, we describe the simple preparation of radiofluorinated β-lactams by using the fast Kinugasa reaction between (18)F-labelled nitrone [(18)F]-1 and alkynes of different reactivity.