Recent Advances in Radiopharmacy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 23833

Special Issue Editor


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Guest Editor
CRCI2NA, INSERM, CNRS, CHU Nantes, University of Nantes, F-44000 Nantes, France
Interests: radiopharmaceuticals; innovative radionuclides; theranostic; copper radiopharmaceuticals

Special Issue Information

Dear Colleagues,

Innovative radionuclides, such as astatine-211 and actinium-225 in therapy, or copper-64 and zirconium-89 in imaging, are becoming increasingly important in radiopharmacy. However, it is difficult to develop them for clinical application. The aim of this Special Issue is to establish the potential uses of these innovative radionuclides, to discuss new trends in radiopharmaceuticals developed with them, and to provide a basis to facilitate their use in clinical trials.

This Special Issue aims to present new trends in the use of innovative radionuclides and their applications in radiopharmacy. The physical or chemical properties of new radionuclides are sometimes unfavorable for the stability of the radiopharmaceuticals obtained with them, which limits their applications. Even if these radionuclides are recognized as being of interest by the scientific community, many questions remain to be answered. Is the growing application of actinium [225Ac] radiolabeled peptides, which are characterized by rapid pharmacokinetic distribution and elimination phases, extensible to other vectors currently used in internal radiotherapy? Is radioactive filiation compatible with non-internalized radiopharmaceuticals? What will be the place of [211At]-Astatine, currently studied at the preclinical level? Are the physical properties of [64Cu]-Copper and its particular metabolism interesting compared with [89Zr]-Zirconium? This Special Issue aims to address these questions, in order to elucidate the future applications of these radionuclides in radiopharmacy.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: innovative radionuclides and their associated radiopharmaceuticals, pharmacokinetics models for innovative radionuclides, in vivo and in vitro stability studies of innovative radionuclides, and new vectors for innovative radionuclides. We look forward to receiving your contributions.

Prof. Dr. Alain Faivre-Chauvet
Guest Editor

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Keywords

  • radiopharmaceuticals with innovative radionuclides
  • stability of radiopharmaceuticals
  • metabolism of radiopharmaceuticals
  • tumor targeting
  • alpha vectorized radiotherapy
  • long period PET radiopharmaceuticals

Published Papers (12 papers)

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Research

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24 pages, 4460 KiB  
Article
Preclinical Evaluation of a 64Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma
by Cassandra Métivier, Patricia Le Saëc, Joëlle Gaschet, Catherine Chauvet, Séverine Marionneau-Lambot, Peter O. Hofgaard, Bjarne Bogen, Julie Pineau, Nathalie Le Bris, Raphaël Tripier, Cyrille Alliot, Férid Haddad, Michel Chérel, Nicolas Chouin, Alain Faivre-Chauvet and Latifa Rbah-Vidal
Pharmaceutics 2023, 15(7), 1817; https://doi.org/10.3390/pharmaceutics15071817 - 25 Jun 2023
Viewed by 1319
Abstract
Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, [...] Read more.
Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optimal radionuclides which, depending on their emission properties, allow the combination of diagnosis by molecular imaging and targeted radionuclide therapy (TRT). Copper-64 has suitable decay properties (both β+ and β- decays) for PET imaging and potentially for TRT, making it both an imaging and therapy agent. We developed and evaluated a theranostic approach using a copper-64 radiolabelled anti-CD138 antibody, [64Cu]Cu-TE1PA-9E7.4 in a MOPC315.BM mouse model of multiple myeloma. PET imaging using [64Cu]Cu-TE1PA-9E7.4 allows for high-resolution PET images. Dosimetric estimation from ex vivo biodistribution data revealed acceptable delivered doses to healthy organs and tissues, and a very encouraging tumour absorbed dose for TRT applications. Therapeutic efficacy resulting in delayed tumour growth and increased survival without inducing major or irreversible toxicity has been observed with 2 doses of 35 MBq administered at a 2-week interval. Repeated injections of [64Cu]Cu-TE1PA-9E7.4 are safe and can be effective for TRT application in this syngeneic preclinical model of MM. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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14 pages, 4014 KiB  
Article
Facile Preparation of Samarium Carbonate-Polymethacrylate Microspheres as a Neutron-Activatable Radioembolic Agent for Hepatic Radioembolization
by Yin How Wong, Azahari Kasbollah, Basri Johan Jeet Abdullah and Chai Hong Yeong
Pharmaceutics 2023, 15(3), 877; https://doi.org/10.3390/pharmaceutics15030877 - 08 Mar 2023
Cited by 1 | Viewed by 1232
Abstract
Radioembolization shows great potential as a treatment for intermediate- and advanced-stage liver cancer. However, the choices of radioembolic agents are currently limited, and hence the treatment is relatively costly compared to other approaches. In this study, a facile preparation method was developed to [...] Read more.
Radioembolization shows great potential as a treatment for intermediate- and advanced-stage liver cancer. However, the choices of radioembolic agents are currently limited, and hence the treatment is relatively costly compared to other approaches. In this study, a facile preparation method was developed to produce samarium carbonate-polymethacrylate [152Sm2(CO3)3-PMA] microspheres as neutron activatable radioembolic microspheres for hepatic radioembolization. The developed microspheres emits both therapeutic beta and diagnostic gamma radiations for post-procedural imaging. The 152Sm2(CO3)3-PMA microspheres were produced from commercially available PMA microspheres through the in situ formation of 152Sm2(CO3)3 within the pores of the PMA microspheres. Physicochemical characterization, gamma spectrometry and radionuclide retention assay were performed to evaluate the performance and stability of the developed microspheres. The mean diameter of the developed microspheres was determined as 29.30 ± 0.18 µm. The scanning electron microscopic images show that the spherical and smooth morphology of the microspheres remained after neutron activation. The 153Sm was successful incorporated into the microspheres with no elemental and radionuclide impurities produced after neutron activation, as indicated by the energy dispersive X-ray analysis and gamma spectrometry. Fourier transform infrared spectroscopy confirmed that there was no alteration to the chemical groups of the microspheres after neutron activation. After 18 h of neutron activation, the microspheres produced an activity of 4.40 ± 0.08 GBq.g−1. The retention of 153Sm on the microspheres was greatly improved to greater than 98% over 120 h when compared to conventionally radiolabeling method at ~85%. The 153Sm2(CO3)3-PMA microspheres achieved suitable physicochemical properties as theragnostic agent for hepatic radioembolization and demonstrated high radionuclide purity and 153Sm retention efficiency in human blood plasma. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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15 pages, 2782 KiB  
Article
Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease
by Alberto Signore, Rita Bonfiglio, Michela Varani, Filippo Galli, Giuseppe Campagna, Manuel Desco, Lorena Cussó, Maurizio Mattei, Andreas Wunder, Filippo Borri, Maria T. Lupo and Elena Bonanno
Pharmaceutics 2023, 15(3), 817; https://doi.org/10.3390/pharmaceutics15030817 - 02 Mar 2023
Cited by 1 | Viewed by 1392
Abstract
Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to [...] Read more.
Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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14 pages, 2742 KiB  
Article
Evaluation of Therapeutic Efficacy and Imaging Capabilities of 153Sm2O3-Loaded Polystyrene Microspheres for Intra-Tumoural Radionuclide Therapy of Liver Cancer Using Sprague-Dawley Rat Model
by Hun Yee Tan, Yin How Wong, Azahari Kasbollah, Mohammad Nazri Md Shah, Noorazrul Yahya, Basri Johan Jeet Abdullah and Chai Hong Yeong
Pharmaceutics 2023, 15(2), 536; https://doi.org/10.3390/pharmaceutics15020536 - 06 Feb 2023
Cited by 1 | Viewed by 1681
Abstract
Introduction: Neutron-activated samarium-153-oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres has been developed in previous study as a potential theranostic agent for hepatic radioembolization. In this study, the therapeutic efficacy and diagnostic imaging capabilities of the formulation was assessed using liver [...] Read more.
Introduction: Neutron-activated samarium-153-oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres has been developed in previous study as a potential theranostic agent for hepatic radioembolization. In this study, the therapeutic efficacy and diagnostic imaging capabilities of the formulation was assessed using liver cancer Sprague-Dawley (SD) rat model. Methods: Twelve male SD rats (150–200 g) that implanted with N1-S1 hepatoma cell line orthotopically were divided into two groups (study versus control) to monitor the tumour growth along 60 days of treatment. The study group received an intra-tumoural injection of approximately 37 MBq of [153Sm]Sm2O3-PS microspheres, while control group received an intra-tumoural injection of 0.1 mL of saline solution. A clinical single photon emission computed tomography/computed tomography (SPECT/CT) system was used to scan the rats at Day 5 post-injection to investigate the diagnostic imaging capabilities of the microspheres. All rats were monitored for change in tumour volume using a portable ultrasound system throughout the study period. Histopathological examination (HPE) was performed after the rats were euthanized at Day 60. Results: At Day 60, no tumour was observed on the ultrasound images of all rats in the study group. In contrast, the tumour volumes in the control group were 24-fold larger compared to baseline. Statistically significant difference was observed in tumour volumes between the study and control groups (p < 0.05). The SPECT/CT images clearly displayed the location of [153Sm]Sm2O3-PS in the liver tumour of all rats at Day 5 post-injection. Additionally, the [153Sm]Sm2O3-PS microspheres was visible on the CT images and this has added to the benefits of 153Sm as a CT contrast agent. The HPE results showed that the [153Sm]Sm2O3-PS microspheres remained concentrated at the injection site with no tumour cells observed in the study group. Conclusions: Neutron-activated [153Sm]Sm2O3-PS microspheres demonstrated excellent therapeutic and diagnostic imaging capabilities for theranostic treatment of liver cancer in a SD rat model. Further studies with different animal and tumour models are planned to validate this finding. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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15 pages, 2066 KiB  
Article
Engineering of a Fully Human Anti-MUC-16 Antibody and Evaluation as a PET Imaging Agent
by Hanan Babeker, Jessica Pougoue Ketchemen, Arunkumar Annan Sudarsan, Samitha Andrahennadi, Anjong Florence Tikum, Anand Krishnan Nambisan, Humphrey Fonge and Maruti Uppalapati
Pharmaceutics 2022, 14(12), 2824; https://doi.org/10.3390/pharmaceutics14122824 - 16 Dec 2022
Cited by 3 | Viewed by 1894
Abstract
Antibodies that recognize cancer biomarkers, such as MUC16, can be used as vehicles to deliver contrast agents (imaging) or cytotoxic payloads (therapy) to the site of tumors. MUC16 is overexpressed in 80% of epithelial ovarian cancer (EOC) and 65% of pancreatic ductal adenocarcinomas [...] Read more.
Antibodies that recognize cancer biomarkers, such as MUC16, can be used as vehicles to deliver contrast agents (imaging) or cytotoxic payloads (therapy) to the site of tumors. MUC16 is overexpressed in 80% of epithelial ovarian cancer (EOC) and 65% of pancreatic ductal adenocarcinomas (PDAC), where effective ‘theranostic’ probes are much needed. This work aims to develop fully human antibodies against MUC16 and evaluate them as potential immuno-PET imaging probes for detecting ovarian and pancreatic cancers. We developed a fully human monoclonal antibody, M16Ab, against MUC16 using phage display. M16Ab was conjugated with p-SCN-Bn-DFO and radiolabeled with 89Zr. 89Zr-DFO-M16Ab was then evaluated for binding specificity and affinity using flow cytometry. In vivo evaluation of 89Zr-DFO-M16Ab was performed by microPET/CT imaging at different time points at 24–120 h post injection (p.i.) and ex vivo biodistribution studies in mice bearing MUC16-expressing OVCAR3, SKOV3 (ovarian) and SW1990 (pancreatic) xenografts. 89Zr-DFO-M16Ab bound specifically to MUC16-expressing cancer cells with an EC50 of 10nM. 89Zr-DFO-M16Ab was stable in serum and showed specific uptake and retention in tumor xenografts even after 120 h p.i. (microPET/CT) with tumor-to-blood ratios > 43 for the SW1990 xenograft. Specific tumor uptake was observed for SW1990/OVCAR3 xenografts but not in MUC16-negative SKOV3 xenografts. Pharmacokinetic study shows a relatively short distribution (t1/2α) and elimination half-life (t1/2ß) of 4.4 h and 99 h, respectively. In summary, 89Zr-DFO-M16Ab is an effective non-invasive imaging probe for ovarian and pancreatic cancers and shows promise for further development of theranostic radiopharmaceuticals. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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18 pages, 1812 KiB  
Article
Automated GMP Production and Preclinical Evaluation of [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA
by Julia Greiser, Thomas Winkens, Olga Perkas, Christian Kuehnel, Wolfgang Weigand and Martin Freesmeyer
Pharmaceutics 2022, 14(12), 2695; https://doi.org/10.3390/pharmaceutics14122695 - 01 Dec 2022
Cited by 1 | Viewed by 1103
Abstract
[68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis [...] Read more.
[68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model. After low radiolabeling yields were attributed to precursor instability at high temperatures, an optimized radiolabeling procedure was established. Quality controls were in accordance with Ph. Eur. requirements and gave compliant results, although the method for the determination of the 68Ga colloid is partially inhibited due to the presence of a radioactive by-product. The determination of logP revealed [68Ga]Ga-TEoS-DAZA (ethoxy bearing) to be more lipophilic than [68Ga]Ga-TMoS-DAZA (methoxy bearing). Accordingly, biodistribution studies in an in ovo model showed a higher liver uptake for [68Ga]Ga-TEoS-DAZA. In dynamic in ovo PET imaging, rapid tracer accumulation in the liver was observed. Similarly, the activity in the intestines rose steadily within the first hour p.i., indicating biliary excretion. As [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA can be prepared according to GMP guidelines, transition into the early clinical phase is now possible. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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15 pages, 2813 KiB  
Article
Bioorthogonal Chemistry Approach for the Theranostics of GRPR-Expressing Cancers
by Alice D’Onofrio, Francisco Silva, Lurdes Gano, Paula Raposinho, Célia Fernandes, Arkadiusz Sikora, Monika Wyczółkowska, Renata Mikołajczak, Piotr Garnuszek and António Paulo
Pharmaceutics 2022, 14(12), 2569; https://doi.org/10.3390/pharmaceutics14122569 - 23 Nov 2022
Cited by 3 | Viewed by 1674
Abstract
Several gastrin-releasing peptide receptor (GRPR) antagonists with improved in vivo behavior have been recently developed and tested in the clinic. However, despite the generally mild side effects of peptide receptor radionuclide therapy (PRRT), toxicity has been observed due to high doses delivered to [...] Read more.
Several gastrin-releasing peptide receptor (GRPR) antagonists with improved in vivo behavior have been recently developed and tested in the clinic. However, despite the generally mild side effects of peptide receptor radionuclide therapy (PRRT), toxicity has been observed due to high doses delivered to nontarget tissues, especially in the kidneys and pancreas. Previous experiences with radiolabeled peptides opened a unique opportunity to explore GRPR pretargeting using clickable bombesin antagonists. Toward this goal, we used clickable DOTA-like radiocomplexes which have been previously evaluated by our group. We functionalized a potent GRPR antagonist with a clickable TCO moiety using two different linkers. These precursors were then studied to select the compound with the highest GRPR binding affinity and the best pharmacokinetics to finally explore the advantages of the devised pretargeting approach. Our results provided an important proof of concept toward the development of bioorthogonal approaches to GRPR-expressing cancers, which are worth investigating further to improve the in vivo results. Moreover, the use of clickable GRPR antagonists and DOTA/DOTAGA derivatives allows for fine-tuning of their pharmacokinetics and metabolic stability, leading to a versatile synthesis of new libraries of (radio)conjugates useful for the development of theranostic tools toward GRPR-expressing tumors. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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16 pages, 2390 KiB  
Article
Peelable Nanocomposite Coatings: “Eco-Friendly” Tools for the Safe Removal of Radiopharmaceutical Spills or Accidental Contamination of Surfaces in General-Purpose Radioisotope Laboratories
by Traian Rotariu, Daniela Pulpea, Gabriela Toader, Edina Rusen, Aurel Diacon, Valentina Neculae and John Liggat
Pharmaceutics 2022, 14(11), 2360; https://doi.org/10.3390/pharmaceutics14112360 - 01 Nov 2022
Cited by 5 | Viewed by 1421
Abstract
Radioactive materials are potentially harmful due to the radiation emitted by radionuclides and the risk of radioactive contamination. Despite strict compliance with safety protocols, contamination with radioactive materials is still possible. This paper describes innovative and inexpensive formulations that can be employed as [...] Read more.
Radioactive materials are potentially harmful due to the radiation emitted by radionuclides and the risk of radioactive contamination. Despite strict compliance with safety protocols, contamination with radioactive materials is still possible. This paper describes innovative and inexpensive formulations that can be employed as ‘eco-friendly’ tools for the safe decontamination of radiopharmaceuticals spills or other accidental radioactive contamination of the surfaces arising from general-purpose radioisotope handling facilities (radiopharmaceutical laboratories, hospitals, research laboratories, etc.). These new peelable nanocomposite coatings are obtained from water-based, non-toxic, polymeric blends containing readily biodegradable components, which do not damage the substrate on which they are applied while also displaying efficient binding and removal of the contaminants from the targeted surfaces. The properties of the film-forming decontamination solutions were assessed using rheological measurements and evaporation rate tests, while the resulting strippable coatings were subjected to Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and tensile tests. Radionuclide decontamination tests were performed on various types of surfaces encountered in radioisotope workspaces (concrete, painted metal, ceramic tiles, linoleum, epoxy resin cover). Thus, it was shown that they possess remarkable properties (thermal and mechanical resistance which permits facile removal through peeling) and that their capacity to entrap and remove beta and alpha particle emitters depends on the constituents of the decontaminating formulation, but more importantly, on the type of surface tested. Except for the cement surface (which was particularly porous), at which the decontamination level ranged between approximately 44% and 89%, for all the other investigated surfaces, a decontamination efficiency ranging from 80.6% to 96.5% was achieved. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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21 pages, 3886 KiB  
Article
Multifunctional Nanoparticles Based on Iron Oxide and Gold-198 Designed for Magnetic Hyperthermia and Radionuclide Therapy as a Potential Tool for Combined HER2-Positive Cancer Treatment
by Michał Żuk, Rafał Podgórski, Anna Ruszczyńska, Tomasz Ciach, Agnieszka Majkowska-Pilip, Aleksander Bilewicz and Paweł Krysiński
Pharmaceutics 2022, 14(8), 1680; https://doi.org/10.3390/pharmaceutics14081680 - 12 Aug 2022
Cited by 13 | Viewed by 2533
Abstract
Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and [...] Read more.
Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe3O4) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody—trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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Review

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36 pages, 6045 KiB  
Review
Clinical Advances and Perspectives in Targeted Radionuclide Therapy
by Nicolas Lepareur, Barthélémy Ramée, Marie Mougin-Degraef and Mickaël Bourgeois
Pharmaceutics 2023, 15(6), 1733; https://doi.org/10.3390/pharmaceutics15061733 - 14 Jun 2023
Cited by 5 | Viewed by 2881
Abstract
Targeted radionuclide therapy has become increasingly prominent as a nuclear medicine subspecialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to [...] Read more.
Targeted radionuclide therapy has become increasingly prominent as a nuclear medicine subspecialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being developed. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mechanisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, and small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in several types of tumors and have been or will soon be approved and authorized for clinical use. Following their clinical and commercial success, research in that domain is particularly growing, with the clinical pipeline appearing as a promising target. This review aims to provide an overview of current research on targeting radionuclide therapy. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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15 pages, 5126 KiB  
Review
Tracers for Cardiac Imaging: Targeting the Future of Viable Myocardium
by Carmela Nappi, Mariarosaria Panico, Maria Falzarano, Carlo Vallone, Andrea Ponsiglione, Paolo Cutillo, Emilia Zampella, Mario Petretta and Alberto Cuocolo
Pharmaceutics 2023, 15(5), 1532; https://doi.org/10.3390/pharmaceutics15051532 - 18 May 2023
Cited by 1 | Viewed by 1075
Abstract
Ischemic heart disease is the leading cause of mortality worldwide. In this context, myocardial viability is defined as the amount of myocardium that, despite contractile dysfunction, maintains metabolic and electrical function, having the potential for functional enhancement upon revascularization. Recent advances have improved [...] Read more.
Ischemic heart disease is the leading cause of mortality worldwide. In this context, myocardial viability is defined as the amount of myocardium that, despite contractile dysfunction, maintains metabolic and electrical function, having the potential for functional enhancement upon revascularization. Recent advances have improved methods to detect myocardial viability. The current paper summarizes the pathophysiological basis of the current methods used to detect myocardial viability in light of the advancements in the development of new radiotracers for cardiac imaging. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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21 pages, 1084 KiB  
Review
Cyclotron Production of Gallium-68 Radiopharmaceuticals Using the 68Zn(p,n)68Ga Reaction and Their Regulatory Aspects
by Zarif Ashhar, Muhammad Fakhrurazi Ahmad Fadzil, Muhamad Faiz Othman, Nor Azah Yusof, Muhammad Adib Abdul Onny, Noratikah Mat Ail and Siti Fatimah Abd Rahman
Pharmaceutics 2023, 15(1), 70; https://doi.org/10.3390/pharmaceutics15010070 - 26 Dec 2022
Cited by 3 | Viewed by 4258
Abstract
Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (68Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for [...] Read more.
Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (68Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for 68Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting 68Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [68Ga]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high 68Ga recovery and apparent molar activity. In the future, 68Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of 68Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns. Full article
(This article belongs to the Special Issue Recent Advances in Radiopharmacy)
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