(89)Zr, a radiometal nuclide with high potential for molecular imaging with PET: chemistry, applications and remaining challenges.

Molecular imaging-and especially Positron Emission Tomography (PET)-is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as well as its visualization and exhibit decay characteristics matching their in vivo pharmacokinetics. To meet this demand, the development of new targeting vectors as well as the use of uncommon radionuclides becomes increasingly important. Uncommon nuclides in this regard enable the utilization of various selectively accumulating bioactive molecules such as peptides, antibodies, their fragments, other proteins and artificial structures for PET imaging in personalized medicine. Among these radionuclides, 89Zr (t1/2 = 3.27 days and mean Eβ+ = 0.389 MeV) has attracted increasing attention within the last years due to its favorably long half-life, which enables imaging at late time-points, being especially favorable in case of slowly-accumulating targeting vectors. This review outlines the recent developments in the field of 89Zr-labeled bioactive molecules, their potential and application in PET imaging and beyond, as well as remaining challenges

Silicon-[18F]Fluorine Radiochemistry: Basics, Applications and Challenges

Silicon-[18F]Fluorine (Si-18F) radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-F-18 and boron-F-18 based labeling strategies, reshaping the landscape of modern F-18-radiochemistry. All these novel methodologies are driven by the demand for more convenient F-18-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as F-18 (one of the most prominent examples) to be introduced into bioactive molecules. Si-F-18 radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-F-18 bond formation, the application of Si-F-18 tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology

τBu₂SiF-Derivatized D₂-Receptor Ligands: The First SiFA-Containing Small Molecule Radiotracers for Target-Specific PET-Imaging

The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D-2-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D2-receptor affinities for all compounds in the nanomolar range (Ki(SiFA-DMFP) = 13.6 nM, Ki(SiFA-FP) = 33.0 nM, Ki(SiFA-DDMFP) = 62.7 nM and Ki(SiFA-M-FP) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with F-18]fluoride/TBAHCO(3) in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/mu mol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min

Silicon-[18F]Fluorine Radiochemistry: Basics, Applications and Challenges

Silicon-[18F]Fluorine (Si-18F) radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-F-18 and boron-F-18 based labeling strategies, reshaping the landscape of modern F-18-radiochemistry. All these novel methodologies are driven by the demand for more convenient F-18-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as F-18 (one of the most prominent examples) to be introduced into bioactive molecules. Si-F-18 radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-F-18 bond formation, the application of Si-F-18 tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology

Automated synthesis of PET radiotracers by copperâ mediated 18Fâ fluorination of organoborons: Importance of the order of addition and competing protodeborylation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142980/1/jlcr3583_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142980/2/jlcr3583.pd

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Main Body: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry

Dosimetry and optimal scan time of 18FSiTATE-PET/CT in patients with neuroendocrine tumours

PURPOSE Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). 18FSiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. METHODS Eight NET patients received a 18FSiTATE-PET/CT (250 ± 66~MBq) with repeated emission scans (10, 30, 60, 120, 180~min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. RESULTS After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004~mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120~min images. CONCLUSION 18FSiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180~min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of 18FSiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120~min, followed by 60~min after injection

(89)Zr, a radiometal nuclide with high potential for molecular imaging with PET: chemistry, applications and remaining challenges.

Molecular imaging-and especially Positron Emission Tomography (PET)-is of increasing importance for the diagnosis of various diseases and thus is experiencing increasing dissemination. Consequently, there is a growing demand for appropriate PET tracers which allow for a specific accumulation in the target structure as well as its visualization and exhibit decay characteristics matching their in vivo pharmacokinetics. To meet this demand, the development of new targeting vectors as well as the use of uncommon radionuclides becomes increasingly important. Uncommon nuclides in this regard enable the utilization of various selectively accumulating bioactive molecules such as peptides, antibodies, their fragments, other proteins and artificial structures for PET imaging in personalized medicine. Among these radionuclides, 89Zr (t1/2 = 3.27 days and mean Eβ+ = 0.389 MeV) has attracted increasing attention within the last years due to its favorably long half-life, which enables imaging at late time-points, being especially favorable in case of slowly-accumulating targeting vectors. This review outlines the recent developments in the field of 89Zr-labeled bioactive molecules, their potential and application in PET imaging and beyond, as well as remaining challenges