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10 pages, 2655 KiB

Open AccessArticle

⁶⁴CuCl₂ PET Imaging of 4T1-Related Allograft of Triple-Negative Breast Cancer in Mice

by Adrien Latgé, Frédéric Boisson, Ali Ouadi, Gerlinde Averous, Lionel Thomas, Alessio Imperiale and David Brasse

Molecules 2022, 27(15), 4869; https://doi.org/10.3390/molecules27154869 - 29 Jul 2022

Cited by 2 | Viewed by 1419

Abstract

⁶⁴CuCl₂ is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of ⁶⁴CuCl₂ in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. ¹⁸F-FDG was used as [...] Read more.

⁶⁴CuCl₂ is an economic radiotracer for oncologic PET investigations. In the present study, we characterized the uptake of ⁶⁴CuCl₂ in vivo by µPET/CT in an allograft 4T1-related mouse model (BALB/c) of advanced breast cancer. ¹⁸F-FDG was used as a comparator. Twenty-two animals were imaged 7–9 days following 4T1-cell implantation inside mammary glands. Dynamic ⁶⁴CuCl₂ µPET/CT acquisition or iterative static images up to 8 h p.i. were performed. Animal biodistribution and tumor uptake were first evaluated in vivo by µPET analysis and then assessed on tissue specimens. Concerning ¹⁸F-FDG µPET, a static acquisition was performed at 15 min and 60 min p.i. Tumor ⁶⁴CuCl₂ accumulation increased from 5 min to 4 h p.i., reaching a maximum value of 5.0 ± 0.20 %ID/g. Liver, brain, and muscle ⁶⁴CuCl₂ accumulation was stable over time. The tumor-to-muscle ratio remained stable from 1 to 8 h p.i., ranging from 3.0 to 3.7. Ex vivo data were consistent with in vivo estimations. The ¹⁸F-FDG tumor accumulation was 8.82 ± 1.03 %ID/g, and the tumor-to-muscle ratio was 4.54 ± 1.11. ⁶⁴CuCl₂ PET/CT provides good characterization of the 4T1-related breast cancer model and allows for exploration of non-glycolytic cellular pathways potentially of interest for theragnostic strategies. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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19 pages, 2849 KiB

Open AccessArticle

Fully Automated Macro- and Microfluidic Production of [⁶⁸Ga]Ga-Citrate on mAIO^® and iMiDEV^TM Modules

by Olga Ovdiichuk, Emilie Roeder, Sébastien Billotte, Nicolas Veran and Charlotte Collet

Molecules 2022, 27(3), 994; https://doi.org/10.3390/molecules27030994 - 01 Feb 2022

Cited by 4 | Viewed by 2333

Abstract

⁶⁸Ga-radionuclide has gained importance due to its availability via ⁶⁸Ge/⁶⁸Ga generator or cyclotron production, therefore increasing the number of ⁶⁸Ga-based PET radiopharmaceuticals available in clinical practice. [⁶⁸Ga]Ga-citrate PET has been shown to be prominent for detection [...] Read more.

⁶⁸Ga-radionuclide has gained importance due to its availability via ⁶⁸Ge/⁶⁸Ga generator or cyclotron production, therefore increasing the number of ⁶⁸Ga-based PET radiopharmaceuticals available in clinical practice. [⁶⁸Ga]Ga-citrate PET has been shown to be prominent for detection of inflammation/infection of the musculoskeletal, gastrointestinal, respiratory, and cardiovascular systems. Automation and comparison between conventional and microfluidic production of [⁶⁸Ga]Ga-citrate was performed using miniAllInOne^® (Trasis) and iMiDEV™ (PMB-Alcen) synthetic modules. Fully automated procedures were elaborated for cGMP production of tracer. In order to facilitate the tracer approval as a radiopharmaceutical for clinical use, a new method for radiochemical identity determination by HPLC analysis to complement standard TLC radiochemical purity measurement was developed. The results showed higher radiochemical yields when using MCX cartridge on the conventional module mAIO^®, while a PS-H+ cation exchanger was shown to be preferred for integration into the microfluidic cassette of iMiDEV™ module. In this study, the fully automated radiosynthesis of [⁶⁸Ga]Ga-citrate using different synthesizers demonstrated reliable and reproducible radiochemical yields. In order to demonstrate the applicability of [⁶⁸Ga]Ga-citrate, in vitro and in vivo studies were performed showing similar characteristics of the tracer obtained using macro- and microfluidic ways of production. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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16 pages, 8847 KiB

Open AccessArticle

Preclinical Assessment Addressing Intravenous Administration of a [⁶⁸Ga]Ga-PSMA-617 Microemulsion: Acute In Vivo Toxicity, Tolerability, PET Imaging, and Biodistribution

by Vusani Mandiwana, Lonji Kalombo, Rose Hayeshi, Jan Rijn Zeevaart and Thomas Ebenhan

Molecules 2021, 26(9), 2650; https://doi.org/10.3390/molecules26092650 - 30 Apr 2021

Cited by 3 | Viewed by 2350

Abstract

It has been herein presented that a microemulsion, known to be an effective and safe drug delivery system following intravenous administration, can be loaded with traces of [⁶⁸Ga]Ga-PSMA-617 without losing its properties or causing toxicity. Following tolerated IV injections the capability [...] Read more.

It has been herein presented that a microemulsion, known to be an effective and safe drug delivery system following intravenous administration, can be loaded with traces of [⁶⁸Ga]Ga-PSMA-617 without losing its properties or causing toxicity. Following tolerated IV injections the capability of the microemulsion in altering [⁶⁸Ga]Ga-PSMA-617 distribution was presented at 120 min post injection based on its ex vivo biodistribution results. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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12 pages, 14191 KiB

Open AccessArticle

Fully Automated Synthesis of Novel TSPO PET Imaging Ligand [¹⁸F]Fluoroethyltemazepam

by Dario Fiorenza, Emanuele Nicolai, Carlo Cavaliere, Ferdinando Fiorino, Giovanna Esposito and Marco Salvatore

Molecules 2021, 26(8), 2372; https://doi.org/10.3390/molecules26082372 - 19 Apr 2021

Cited by 5 | Viewed by 2577

Abstract

Introduction: Benzodiazepines, including temazepam are described as TSPO antagonists. In fact, TSPO was initially described as a peripheral benzodiazepine receptor (PBR) with a secondary binding site for diazepam. TSPO is a potential imaging target of neuroinflammation because there is an amplification of the [...] Read more.

Introduction: Benzodiazepines, including temazepam are described as TSPO antagonists. In fact, TSPO was initially described as a peripheral benzodiazepine receptor (PBR) with a secondary binding site for diazepam. TSPO is a potential imaging target of neuroinflammation because there is an amplification of the expression of this receptor. Objectives: Herein, we developed a novel fluorinated benzodiazepine ligand, [¹⁸F]Fluoroethyltemazepam ([¹⁸F]F-FETEM), for positron emission tomography (PET) imaging of translocator protein (18 kDa). Methods: [¹⁸F]F-FETEM was radiolabelled with an automated synthesizer via a one-pot procedure. We conducted a [¹⁸F]F-aliphatic nucleophilic substitution of a tosylated precursor followed by purification on C18 and Alumina N SPE cartridges. Quality control tests was also carried out. Results: We obtained 2.0–3.0% decay-uncorrected radiochemical activity yield (3.7% decay-corrected) within the whole synthesis time about 33 min. The radiochemical purity of [¹⁸F]F-FETEM was over 90% by TLC analysis. Conclusions: This automated procedure may be used as basis for future production of [¹⁸F]F-FETEM for preclinical PET imaging studies. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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12 pages, 3316 KiB

Open AccessArticle

An Improved Synthesis of N-(4-[¹⁸F]Fluorobenzoyl)-Interleukin-2 for the Preclinical PET Imaging of Tumour-Infiltrating T-cells in CT26 and MC38 Colon Cancer Models

by Shivashankar Khanapur, Fui Fong Yong, Siddesh V. Hartimath, Lingfan Jiang, Boominathan Ramasamy, Peter Cheng, Pradeep Narayanaswamy, Julian L. Goggi and Edward George Robins

Molecules 2021, 26(6), 1728; https://doi.org/10.3390/molecules26061728 - 19 Mar 2021

Cited by 4 | Viewed by 2636

Abstract

Positron emission tomography (PET) imaging of activated T-cells with N-(4-[¹⁸F]fluorobenzoyl)-interleukin-2 ([¹⁸F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding [...] Read more.

Positron emission tomography (PET) imaging of activated T-cells with N-(4-[¹⁸F]fluorobenzoyl)-interleukin-2 ([¹⁸F]FB-IL-2) may be a promising tool for patient management to aid in the assessment of clinical responses to immune therapeutics. Unfortunately, existing radiosynthetic methods are very low yielding due to complex and time-consuming chemical processes. Herein, we report an improved method for the synthesis of [¹⁸F]FB-IL-2, which reduces synthesis time and improves radiochemical yield. With this optimized approach, [¹⁸F]FB-IL-2 was prepared with a non-decay-corrected radiochemical yield of 3.8 ± 0.7% from [¹⁸F]fluoride, 3.8 times higher than previously reported methods. In vitro experiments showed that the radiotracer was stable with good radiochemical purity (>95%), confirmed its identity and showed preferential binding to activated mouse peripheral blood mononuclear cells. Dynamic PET imaging and ex vivo biodistribution studies in naïve Balb/c mice showed organ distribution and kinetics comparable to earlier published data on [¹⁸F]FB-IL-2. Significant improvements in the radiochemical manufacture of [¹⁸F]FB-IL-2 facilitates access to this promising PET imaging radiopharmaceutical, which may, in turn, provide useful insights into different tumour phenotypes and a greater understanding of the cellular nature and differential immune microenvironments that are critical to understand and develop new treatments for cancers. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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16 pages, 3816 KiB

Open AccessArticle

Developments toward the Implementation of ⁴⁴Sc Production at a Medical Cyclotron

by Nicholas P. van der Meulen, Roger Hasler, Zeynep Talip, Pascal V. Grundler, Chiara Favaretto, Christoph A. Umbricht, Cristina Müller, Gaia Dellepiane, Tommaso S. Carzaniga and Saverio Braccini

Molecules 2020, 25(20), 4706; https://doi.org/10.3390/molecules25204706 - 14 Oct 2020

Cited by 38 | Viewed by 3332

Abstract

⁴⁴Sc has favorable properties for cancer diagnosis using Positron Emission Tomography (PET) making it a promising candidate for application in nuclear medicine. The implementation of its production with existing compact medical cyclotrons would mean the next essential milestone in the development of [...] Read more.

⁴⁴Sc has favorable properties for cancer diagnosis using Positron Emission Tomography (PET) making it a promising candidate for application in nuclear medicine. The implementation of its production with existing compact medical cyclotrons would mean the next essential milestone in the development of this radionuclide. While the production and application of ⁴⁴Sc has been comprehensively investigated, the development of specific targetry and irradiation methods is of paramount importance. As a result, the target was optimized for the ⁴⁴Ca(p,n)⁴⁴Sc nuclear reaction using CaO instead of CaCO₃, ensuring decrease in target radioactive degassing during irradiation and increased radionuclidic yield. Irradiations were performed at the research cyclotron at the Paul Scherrer Institute (~11 MeV, 50 µA, 90 min) and the medical cyclotron at the University of Bern (~13 MeV, 10 µA, 240 min), with yields varying from 200 MBq to 16 GBq. The development of targetry, chemical separation as well as the practical issues and implications of irradiations, are analyzed and discussed. As a proof-of-concept study, the ⁴⁴Sc produced at the medical cyclotron was used for a preclinical study using a previously developed albumin-binding prostate-specific membrane antigen (PSMA) ligand. This work demonstrates the feasibility to produce ⁴⁴Sc with high yields and radionuclidic purity using a medical cyclotron, equipped with a commercial solid target station. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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Review

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12 pages, 1521 KiB

Open AccessReview

Positron Emission Tomography Radiopharmaceuticals in Differentiated Thyroid Cancer

by Chaninart Sakulpisuti, Putthiporn Charoenphun and Wichana Chamroonrat

Molecules 2022, 27(15), 4936; https://doi.org/10.3390/molecules27154936 - 03 Aug 2022

Cited by 3 | Viewed by 2637

Abstract

Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common type of thyroid cancer. Despite the well-known utilization of radioiodine treatment in DTC, i.e., iodine-131, radioiodine imaging in DTC is typically performed with iodine-123 and iodine-131, with the current [...] Read more.

Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common type of thyroid cancer. Despite the well-known utilization of radioiodine treatment in DTC, i.e., iodine-131, radioiodine imaging in DTC is typically performed with iodine-123 and iodine-131, with the current hybrid scanner performing single photon emission tomography/computed tomography (SPECT/CT). Positron emission tomography/computed tomography (PET/CT) provides superior visualization and quantification of functions at the molecular level; thus, lesion assessment can be improved compared to that of SPECT/CT. Various types of cancer, including radioiodine-refractory DTC, can be detected by 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), the most well-known and widely used PET radiopharmaceutical. Several other PET radiopharmaceuticals have been developed, although some are limited in availability despite their potential clinical utilizations. This article aims to summarize PET radiopharmaceuticals in DTC, focusing on molecular pathways and applications. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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27 pages, 26944 KiB

Open AccessReview

PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin α_vβ₃ Receptors

by Christos Liolios, Christos Sachpekidis, Antonios Kolocouris, Antonia Dimitrakopoulou-Strauss and Penelope Bouziotis

Molecules 2021, 26(6), 1792; https://doi.org/10.3390/molecules26061792 - 22 Mar 2021

Cited by 25 | Viewed by 4222

Abstract

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging [...] Read more.

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin α_vβ₃ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin α_vβ₃ tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (¹⁸F, ⁶⁴Cu, and ⁶⁸Ga), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included. Full article

(This article belongs to the Special Issue Radiopharmaceuticals for PET Imaging - Issue B)

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