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The cathelicidin-derived peptide (CDP1) is a human antimicrobial peptide that preferentially targets bacterial membranes in response to infection. CDP1 was functionalised with NODAGA and DOTA for complexation with gallium-68 to evaluate its potential as an infection imaging tracer. The synthesis of [68Ga]Ga–NODAGA–CDP1 and [68Ga]Ga–DOTA–CDP1 were optimised for pH, molarity, incubation time and temperature, and product purification. The integrity and protein binding were investigated employing [68Ga]GaCl3 and [68Ga]Ga–DOTA–TATE as internal references. [68Ga]Ga–NODAGA–CDP1 displayed good labelling properties with higher product yield compared to [68Ga]Ga–DOTA–CDP1. In contrast, [68Ga]Ga–DOTA–CDP1 showed better stability and is the preferred candidate for an in vivo investigation. [ABSTRACT FROM AUTHOR]

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. A gallium-68 labelled kisspeptin-10 (KP10), the minimal biologically active structure, has potential as a pan-tumour radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was attached to the NH2-terminus of KP10 as we posited from our previous publications that this modification would not impair biological activity. Here, we showed that the biological activity, as monitored by stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene, was indeed similar for KP10 and DOTA-KP10. The optimisation of radiolabelling with gallium-68 and lutetium-177 is described. Stability in serum, plasma and whole blood was also investigated. Pharmacokinetics and biodistribution were established with micro-PET/CT (positron emission tomography/computerised tomography) and ex vivo measurements. Dynamic studies with micro-PET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 min. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These results lay the foundation for the further development of DOTA-KP10 analogues that have high binding affinity along with proteolytic resistance., (© 2025 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Background: The transplantation of hematopoietic stem and progenitor cells (HSPCs) or mesenchymal stromal/stem cells (MSCs) for the treatment of a wide variety of diseases has been studied extensively. A challenge with cell-based therapies is that migration to and retention at the target site is often difficult to monitor and quantify. Zirconium-89 ( 89 Zr) is a positron-emitting radionuclide with a half-life of 3.3 days, which allows long-term cell tracking. Para-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) is the chelating agent of choice for 89 Zr-cell surface labelling. We utilised a shortened labelling method, thereby avoiding a 30-60-min incubation step for [ 89 Zr]Zr-Df-Bz-NCS chelation, to radiolabel HSPCs and MSCs with zirconium-89., Results: Three 89 Zr-MSC labelling attempts were performed. High labelling efficiencies (81.30 and 87.30%) and relatively good labelling yields (59.59 and 67.00%) were achieved with the use of a relatively larger number of MSCs (4.425 and 3.855 million, respectively). There was no significant decrease in MSC viability after 89 Zr-labeling (p = 0.31). This labelling method was also translatable to prepare 89 Zr-HSPC; preliminary data from one preparation indicated high 89 Zr-HSPC labelling efficiency (88.20%) and labelling yield (71.06%), as well as good HSPC viability after labelling (68.65%)., Conclusions: Successful 89 Zr-MSC and 89 Zr-HSPC labelling was achieved, which underlines the prospects for in vivo cell tracking studies with positron emission tomography. In vitro investigations with larger sample sizes and preclinical studies are recommended., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the institutional review board at the Sefako Makgatho Health Sciences University (Ref no. SMUREC/P/21/2017) and informed consent was given to use cryopreserved stem cells from healthy donors. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Gallium-68 has gained substantial momentum since 2003 as a versatile radiometal that is extremely useful for application in the development of novel oncology targeting diagnostic radiopharmaceuticals. It is available through both generator produced radioactivity and via cyclotron production methods and can therefore be implemented in either small- or large-scale production facilities. It can also be implemented within different spectrum of infrastructure settings with relative ease. Whilst many of the radiopharmaceuticals are being development and investigated, which is summarized in this manuscript, [ 68 Ga]Ga-SSTR2 and [ 68 Ga]Ga-PSMA has prominence in current clinical guidelines. The novel tracer [ 68 Ga]Ga-FAPi has also gained significant interest in the clinical context. A comparison of the labelling strategies followed to incorporate gallium-68 and fluorine-18 into the same molecular targeting constructs clearly demonstrate that gallium-68 complexation is the most convenient approach. Recently, cold kit based starting products are available to make the small-scale production of gallium-68 radiopharmaceuticals even more efficient when combined with generator produced gallium-68. The regulatory aspects is currently changing to support the implementation of gallium-68 and other diagnostic radiopharmaceuticals, simplifying the translation towards clinical use. Overall, the development of gallium-68 based radiopharmaceuticals is not only rapidly changing the landscape of diagnosis in oncology, but this growth also promotes innovation and progress in new applications of therapeutic radiometals such as lutetium-177 and actinium-225., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Janke Kleynhans reports financial support was provided by Research Foundation Flanders. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Zirconium-89 ( 89 Zr) is a cyclotron-produced positron-emitting radioisotope with a half-life of 3.27 days, which makes delayed or longitudinal imaging possible. It is a superior isotope for tracking particles over several days at a high sensitivity, resolution, and specificity. 89 Zr-monoclonal antibodies ( 89 Zr-mAb) have gained significant attention in the field of molecular imaging. However, the past decade has shown an avid increase in research concerning 89 Zr-radiopharmaceuticals apart from 89 Zr-mAb. In this article we highlight and discuss the status and challenges attributed to current preclinical and clinical investigations of 89 Zr-radiopharmaceuticals developed beyond 89 Zr-mAb, e.g., mAb-derived variants and macro-biomolecules, proteins, peptides, nanoparticles, and living cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This research presents the development of positron emission tomography (PET) radiotracers for detecting Mycobacterium tuberculosis (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display-derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET-compatible radiometals such as gallium-68. Herein, we report on the chelator functionalization, optimized radiosynthesis, and assessment of the radiopharmaceutical properties of [ 68 Ga]Ga-NODASA-H8 and [ 68 Ga]Ga-NODASA-PH1. Robust radiolabeling was achieved using the established routine method, indicating consistent production of a radiochemically pure product (RCP ≥ 99.6%). For respective [ 68 Ga]Ga-NODASA-H8 and [ 68 Ga]Ga-NODASA-PH1, relatively high levels of decay-corrected radiochemical yield (91.2% ± 2.3%, 86.7% ± 4.0%) and apparent molar activity (A m , 3.9 ± 0.8 and 34.0 ± 5.3 GBq/μmol) were reliably achieved within 42 min, suitable for imaging purposes. Notably, [ 68 Ga]Ga-NODASA-PH1 remained stable in blood plasma for up to 2 h, while [ 68 Ga]Ga-NODASA-H8 degraded within 30 min. For both 68 Ga peptides, minimal whole-blood cell binding and plasma protein binding were observed, indicating a favorable pharmaceutical behavior. [ 68 Ga]Ga-NODASA-PH1 is a promising candidate for further in vitro/in vivo evaluation as a tuberculosis-specific infection imaging agent., (© 2024 The Author(s). Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

The ability of bacteria to recycle exogenous amino acid-based peptides and amino sugars for peptidoglycan biosynthesis was extensively investigated using optical imaging. In particular, fluorescent AeK-NBD was effectively utilized to study the peptidoglycan recycling pathway in Gram-negative bacteria. Based on these promising results, we were inspired to develop the radioactive AeK conjugate [ 68 Ga]Ga-DOTA-AeK for the in vivo localization of bacterial infection using PET/CT. An easy-to-implement radiolabeling procedure for DOTA-AeK with [ 68 Ga]GaCI 3 followed by solid-phase purification was successfully established to obtain [ 68 Ga]Ga-DOTA-AeK with a radiochemical purity of ≥95%. [ 68 Ga]Ga-DOTA-AeK showed good stability over time with less protein binding under physiological conditions. The bacterial incorporation of [ 68 Ga]Ga-DOTA-AeK and its fluorescent Aek-NBD analog were investigated in live and heat-killed Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). Unfortunately, no conclusive in vitro intracellular uptake of [ 68 Ga]Ga-DOTA-AeK was observed for E. coli or S. aureus live and heat-killed bacterial strains ( p > 0.05). In contrast, AeK-NBD showed significantly higher intracellular incorporation in live bacteria compared to the heat-killed control ( p < 0.05). Preliminary biodistribution studies of [ 68 Ga]Ga-DOTA-AeK in a dual-model of chronic infection and inflammation revealed limited localization at the infection site with non-specific accumulation in response to inflammatory markers. Finally, our study demonstrates proof that the intracellular incorporation of AeK is necessary for successful bacteria-specific imaging using PET/CT. Therefore, Ga-68 was not a suitable radioisotope for tracing the bacterial uptake of AeK tripeptide, as it required chelation with a bulky metal chelator such as DOTA, which may have limited its active membrane transportation. An alternative for optimization is to explore diverse chemical structures of AeK that would allow for radiolabeling with 18 F or 11 C.

Radiolabelled puromycin analogues will allow the quantification of protein synthesis through nuclear medicine-based imaging. A particularly useful application could be the non-invasive longitudinal visualisation of mycobacterial activity through direct quantification of puromycin binding. This study assesses the value of [ 68 Ga]Ga-DOTA-puromycin in the visualisation of mycobacteria through positron emission tomography combined with magnetic resonance imaging (µPET/MRI). The radiopharmaceutical was produced by previously published and validated methods. [ 68 Ga]Ga-DOTA-Puromycin imaging was performed on severe immunodeficient mice infected with Bacille Calmette-Guérin-derived M. Bovis (BCG). Acute and chronic infection stages were examined by µPET/MRI. A follow-up group of animals acted as controls (animals bearing S. aureus-derived infection and sterile inflammation) to assess tracer selectivity. [ 68 Ga]Ga-DOTA-puromycin-µPET/MRI images revealed the acute, widespread infection within the right upper shoulder and armpit. Also, [ 68 Ga]Ga-DOTA-puromycin signal sensitivity measured after a 12-week period was lower than that of [ 18 F]FDG-PET in the same animals. A suitable correlation between normalised uptake values (NUV) and gold standard histopathological analysis confirms accurate tracer accumulation in viable bacteria. The radiopharmaceutical showed infection selectivity over inflammation but accumulated in both M. Bovis and S. Aureus, lacking pathogen specificity. Overall, [ 68 Ga]Ga-DOTA-puromycin exhibits potential as a tool for non-invasive protein synthesis visualization, albeit without pathogen selectivity., (© 2024. The Author(s).)

Introduction: Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([ 99m Tc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 ( 89 Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [ 89 Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89 Zr-labelled leukocytes, using p -isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [ 99m Tc]Tc-HMPAO-labelled leukocytes., Methods: Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [ 99m Tc]Tc-HMPAO according to standardised methods, and [ 89 Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [ 99m Tc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients., Results: Successful [ 89 Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n  = 8). A mean high viability of [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [ 89 Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [ 99m Tc]Tc-HMPAO- and [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [ 99m Tc]Tc-HMPAO-labelled leukocytes outperformed [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel., Discussion: Although the [ 89 Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [ 89 Zr]Zr-Df-Bz-NCS-labelled leukocytes., Competing Interests: TE and JZ were employed by The South African Nuclear Energy Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Kahts, Summers, Ndlela, Gutta, Nemutaduni, More, Parsoo, Ebenhan, Zeevaart, Aras and Sathekge.)

Background: Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019., Main Body: Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [ 68 Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [ 68 Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [ 11 C]para-aminobenzoic acid and D-methyl-[ 11 C]-methionine, with clinical trials underway for [ 18 F]fluorodeoxy-sorbitol, as well as for 11 C- and 18 F-labelled trimethoprim., Conclusion: It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors' opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents., (© 2024. The Author(s).)

Preclinical studies are essential for effectively evaluating TAT radiopharmaceuticals. Given the current suboptimal supply chain of these radionuclides, animal studies must be refined to produce the most translatable TAT agents with the greatest clinical potential. Vector design is pivotal, emphasizing harmonious physical and biological characteristics among the vector, target, and radionuclide. The scarcity of alpha-emitting radionuclides remains a significant consideration. Actinium-225 and lead-212 appear as the most readily available radionuclides at this stage. Available animal models for researchers encompass xenografts, allografts, and PDX (patient-derived xenograft) models. Emerging strategies for imaging alpha-emitters are also briefly explored. Ultimately, preclinical research must address two critical aspects: (1) offering valuable insights into balancing safety and efficacy, and (2) providing guidance on the optimal dosing of the TAT agent., (© 2024. The Author(s).)

The unique structural architecture of the peptidoglycan allows for the stratification of bacteria as either Gram-negative or Gram-positive, which makes bacterial cells distinguishable from mammalian cells. This classification has received attention as a potential target for diagnostic and therapeutic purposes. Bacteria's ability to metabolically integrate peptidoglycan precursors during cell wall biosynthesis and recycling offers an opportunity to target and image pathogens in their biological state. This Review explores the peptidoglycan biosynthesis for bacteria-specific targeting for infection imaging. Current and potential radiolabeled peptidoglycan precursors for bacterial infection imaging, their development status, and their performance in vitro and/or in vivo are highlighted. We conclude by providing our thoughts on how to shape this area of research for future clinical translation.

The International Atomic Energy Agency organized a technical meeting at its headquarters in Vienna, Austria, in 2022 that included 17 experts representing 12 countries, whose research spanned the development and use of radiolabeled agents for imaging infection. The meeting focused largely on bacterial pathogens. The group discussed and evaluated the advantages and disadvantages of several radiopharmaceuticals, as well as the science driving various imaging approaches. The main objective was to understand why few infection-targeted radiotracers are used in clinical practice despite the urgent need to better characterize bacterial infections. This article summarizes the resulting consensus, at least among the included scientists and countries, on the current status of radiopharmaceutical development for infection imaging. Also included are opinions and recommendations regarding current research standards in this area. This and future International Atomic Energy Agency-sponsored collaborations will advance the goal of providing the medical community with innovative, practical tools for the specific image-based diagnosis of infection., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

It is important to constantly monitor developments in the preclinical imaging arena of infection. Firstly, novel radiopharmaceuticals with the correct characteristics must be identified to funnel into the clinic. Secondly, it must be evaluated if enough innovative research is being done and adequate resources are geared towards the development of radiopharmaceuticals that could feed into the Nuclear Medicine Clinic in the near future. It is proposed that the ideal infection imaging agent will involve PET combined with CT but more ideally MRI. The radiopharmaceuticals currently presented in preclinical literature have a wide selection of vectors and targets. Ionic formulations of PET-radionuclides such 64 CuCl 2 and 68 GaCl 2 are evaluated for bacterial infection imaging. Many small molecule based radiopharmaceuticals are being investigated with the most prominent targets being cell wall synthesis, maltodextrin transport (such as [ 18 F]F-maltotriose), siderophores (bacterial and fungal infections), the folate synthesis pathway (such as [ 18 F]F-PABA) and protein synthesis (radiolabelled puromycin). Mycobacterial specific antibiotics, antifungals and antiviral agents are also under investigation as infection imaging agents. Peptide based radiopharmaceuticals are developed for bacterial, fungal and viral infections. The radiopharmaceutical development could even react quickly enough on a pandemic to develop a SARS-CoV-2 imaging agent in a timely fashion ([ 64 Cu]Cu-NOTA-EK1). New immuno-PET agents for the imaging of viruses have recently been published, specifically for HIV persistence but also for SARS-CoV2. A very promising antifungal immuno-PET agent (hJ5F) is also considered. Future technologies could include the application of aptamers and bacteriophages and even going as far as the design of theranostic infection. Another possibility would be the application of nanobodies for immuno-PET applications. Standardization and optimization of the preclinical evaluation of radiopharmaceuticals could enhance clinical translation and reduce time spent in pursuing less than optimal candidates., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite recent advances in multimodality therapy for glioblastoma (GB) incorporating surgery, radiotherapy, chemotherapy and targeted therapy, the overall prognosis remains poor. One of the interesting targets for GB therapy is the histone deacetylase family (HDAC). Due to their pleiotropic effects on, e.g., DNA repair, cell proliferation, differentiation, apoptosis and cell cycle, HDAC inhibitors have gained a lot of attention in the last decade as anti-cancer agents. Despite their known underlying mechanism, their therapeutic activity is not well-defined. In this review, an extensive overview is given of the current status of HDAC inhibitors for GB therapy, followed by an overview of current HDAC-targeting radiopharmaceuticals. Imaging HDAC expression or activity could provide key insights regarding the role of HDAC enzymes in gliomagenesis, thus identifying patients likely to benefit from HDACi-targeted therapy.

Radiopharmaceutical development hinges on the affinity and selectivity of the biological component for the intended target. An analogue of the neuropeptide Substance P (SP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi 8 ,Met(O 2 ) 11 ]-SP (DOTA-[Thi 8 ,Met(O 2 ) 11 ]SP), in the theranostic pair [ 68 Ga]Ga-/ [ 213 Bi]Bi-DOTA-[Thi 8 ,Met(O 2 ) 11 ]SP has shown promising clinical results in the treatment of inoperable glioblastoma. As the theranostic targeting component, modifications to SP that affect the selectivity of the resulting analogue for the intended target (neurokinin-1 receptor [NK1R]) could be detrimental to its therapeutic potential. In addition to other closely related tachykinin receptors (neurokinin-2 receptor [NK2R] and neurokinin-3 receptor [NK3R]), SP can activate a mast cell expressed receptor Mas-related G protein-coupled receptor subtype 2 (MRGPRX2), which has been implicated in allergic-type reactions. Therefore, activation of these receptors by SP analogues has severe implications for their therapeutic potential. Here, the receptor selectivity of DOTA-[Thi 8 ,Met(O 2 ) 11 ]SP was examined using inositol phosphate accumulation assay in HEK293-T cells expressing NK1R, NK2R, NK3R or MRGPRX2. DOTA-[Thi 8 ,Met(O 2 ) 11 ]SP had similar efficacy and potency as native SP at NK1R, but displayed greater NK1R selectivity. DOTA-[Thi 8 ,Met(O 2 ) 11 ]SP was unable to elicit significant activation of the other tachykinin receptors nor MRGPRX2 at high concentrations nor did it display antagonistic behaviour at these receptors. DOTA-[Thi 8 ,Met(O 2 ) 11 ]SP, therefore has high potency and selectivity for NK1R, supporting its potential for targeted theranostic use in glioblastoma multiforme and other conditions characterised by NK1R overexpression.

Patients with cancer are presumed to be vulnerable to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe clinical outcomes due to the immunocompromised state mediated by their underlying malignancies and therapy. The aim of this study was to estimate the SARS-CoV-2 seroprevalence, following second to fourth waves in solid tumour patients attending the Steve Biko Academic Hospital (SBAH) for diagnosis and treatment of cancer. We used the single-prick COVID-19 IgG/IgM Rapid Test Cassettes to detect SARS-CoV-2 IgG/IgM antibodies in 760 patients with solid tumours who were asymptomatic and who had never tested positive for coronavirus disease 2019 (COVID-19). Out of the 760 patients, 277 were male (36.4%), 483 were female (63.6%), and the mean age was 55 years (range 18−92). The estimated total seroprevalence was 33.2%. The seroprevalence status of the COVID-19 IgG/IgM antibodies rose significantly from the second wave (11.3%) to the third (67.38%) and then the fourth (69.81%) waves with roughly similar counts. A significant number of the seropositive patients were asymptomatic to COVID-19 (96%). There was a higher rate of seropositivity in cancer patients with hypertension (p < 0.05). Patients with breast, gynaecologic, and prostate cancers exhibited increased SARS-CoV-2 seropositivity. Although oncology patients may be susceptible to SARS-CoV-2 infection, our data indicate that these patients remained asymptomatic throughout various waves with an overall COVID-19 IgG/IgM antibody seropositivity of 33.16%, suggesting no risk of severe or fatal cases of COVID-19.

Background: Ubiquicidin is a peptide fragment with selective binding to negatively charged bacterial cell membranes. Besides its earlier labelling with gamma emitting radionuclides, it has been labelled with Positron Emission Tomography (PET) radionuclides in the last decade for imaging infection and distinguishing infectious disease from sterile inflammation. This systematic review aims to evaluate the technology readiness level of PET based ubiquicidin radiopharmaceuticals., Methods: Two independent researchers reviewed all articles and abstracts pertaining ubiquicidin and PET imaging that are currently available. Scopus, Google Scholar and PubMed/Medline were used in the search. Upon completion of the literature search all articles and abstracts were evaluated and duplicates were excluded. All non-PET articles as well as review articles without new data were deemed ineligible., Results: From a total of 17 papers and 10 abstracts the studies were grouped into development, preclinical and clinical studies. Development was published in 15/17 (88%) publications and 6/10 (60%) abstracts, preclinical applications in 9/17 (53%) publications and 1/10 (10%) of abstracts. Finally, clinical studies made up 6/17 (35%) of full publications and 4/10 (40%) of the available abstracts. Development results were the most abundant. All the findings in the different areas of development of ubiquicidin as PET radiopharmaceutical are summarized in this paper., Conclusion: Labelling procedures are generally uncomplicated and relatively fast and there are indications of adequate product stability. The production of PET radiopharmaceuticals based on UBI will therefore not be a barrier for clinical introduction of this technology. Systematization and unification of criteria for preclinical imaging and larger clinical trials are needed to ensure the translation of this radiopharmaceutical into the clinic. Therefore a conclusion with regards to the clinical relevance of ubiquicidin based PET is not yet possible., Competing Interests: Declaration of competing interest The authors declare no conflict of interest relevant to this article., (Copyright © 2022. Published by Elsevier Inc.)

The excellent features of non-invasive molecular imaging, its progressive technology (real-time, whole-body imaging and quantification), and global impact by a growing infrastructure for positron emission tomography (PET) scanners are encouraging prospects to investigate new concepts, which could transform clinical care of complex infectious diseases. Researchers are aiming towards the extension beyond the routinely available radiopharmaceuticals and are looking for more effective tools that interact directly with causative pathogens. We reviewed and critically evaluated (challenges or pitfalls) antibiotic-derived PET radiopharmaceutical development efforts aimed at infection imaging. We considered both radiotracer development for infection imaging and radio-antibiotic PET imaging supplementing other tools for pharmacologic drug characterization; overall, a total of 20 original PET radiotracers derived from eleven approved antibiotics., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted radionuclide therapy (TRT) is gaining momentum, for example, to stratify patients based on specific biomarkers. One of these biomarkers is deficiencies in DNA damage repair (DDR), which give rise to genomic instability and cancer initiation. However, these deficiencies also provide targets to specifically kill cancer cells following the synthetic lethality principle. This led to the increased interest in targeted drugs that inhibit essential DDR kinases (DDRi), of which multiple are undergoing clinical validation. In this review, the current status of DDRi for the treatment of GB is given for selected targets: ATM/ATR, CHK1/2, DNA-PK, and PARP. Furthermore, this review provides a perspective on the use of radiopharmaceuticals targeting these DDR kinases to (1) evaluate the DNA repair phenotype of GB before treatment decisions are made and (2) induce DNA damage via TRT. Finally, by applying in-house selection criteria and analyzing the structural characteristics of the DDRi, four drugs with the potential to become new therapeutic GB radiopharmaceuticals are suggested.

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi 8 , Met(O 2 ) 11 ]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO 2 generator matrix as well as preliminary results on the adaptability to produce [ 213 Bi]Bi-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi 8 , Met(O 2 ) 11 ]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [ 68 Ga]Ga-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP mixed with [ 213 Bi]Bi-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP. [ 68 Ga]Ga-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [ 213 Bi]Bi-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP providing sufficient activity for 1-2 human doses. The resultant formulation of [ 68 Ga]Ga-/[ 213 Bi]Bi-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi 8 , Met(O 2 ) 11 ]SP-a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [ 68 Ga]Ga-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP and [ 213 Bi]Bi-DOTA-[Thi 8 , Met(O 2 ) 11 ]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.

The rationale for application of nanotechnology in targeted alpha therapy (TAT) is sound. However, the translational strategy requires attention. Formulation of TAT in nanoparticulate drug delivery systems has the potential to resolve many of the issues currently experienced. As α-particle emitters are more cytotoxic compared to beta-minus-emitting agents, the results of poor biodistribution are more dangerous. Formulation in nanotechnology is also suggested to be the ideal solution for containing the recoil daughters emitted by actinium-225, radium-223, and thorium-227. Nanoparticle-based TAT is likely to increase stability, enhance radiation dosimetry profiles, and increase therapeutic efficacy. Unfortunately, nanoparticles have their own unique barriers towards clinical translation. A major obstacle is accumulation in critical organs such as the spleen, liver, and lungs. Furthermore, inflammation, necrosis, reactive oxidative species, and apoptosis are key mechanisms through which nanoparticle-mediated toxicity takes place. It is important at this stage of the technology's readiness level that focus is shifted to clinical translation. The relative scarcity of α-particle emitters also contributes to slow-moving research in the field of TAT nanotechnology. This review describes approaches and solutions which may overcome obstacles impeding nanoparticle-based TAT and enhance clinical translation. In addition, an in-depth discussion of relevant issues and a view on technical and regulatory barriers are presented.

Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT). Advances in radiopharmaceutical development have unlocked the possibility to assess disease at the molecular level allowing individual diagnosis. This leads to the possibility of choosing a tailored, targeted approach for therapeutic modalities. Therapeutic modalities based on radiopharmaceuticals are an exciting development with great potential to promote a personalised approach to medicine. However, an effective targeted radionuclide therapy (TRT) for the treatment of GB entails caveats and requisites. This review provides an overview of existing nuclear imaging and TRT strategies for GB. A critical discussion of the optimal characteristics for new GB targeting therapeutic radiopharmaceuticals and clinical indications are provided. Considerations for target selection are discussed, i.e. specific presence of the target, expression level and pharmacological access to the target, with particular attention to blood-brain barrier crossing. An overview of the most promising radionuclides is given along with a validation of the relevant radiopharmaceuticals and theranostic agents (based on small molecules, peptides and monoclonal antibodies). Moreover, toxicity issues and safety pharmacology aspects will be presented, both in general and for the brain in particular., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

Introduction: Non-invasive imaging techniques (especially single-photon emission tomography and positron emission tomography) apply several RGD-based imaging ligands developed during a vast number of preclinical and clinical investigations. The RGD (Arg-Gly-Asp) sequence is a binding moiety for a large selection of adhesive extracellular matrix and cell surface proteins. Since the first identification of this sequence as the shortest sequence required for recognition in fibronectin during the 1980s, fundamental research regarding the molecular mechanisms of integrin action have paved the way for development of several pharmaceuticals and radiopharmaceuticals with clinical applications. Ligands recognizing RGD may be developed for use in the monitoring of these interactions (benign or pathological). Although RGD-based molecular imaging has been actively investigated for oncological purposes, their utilization towards non-oncology applications remains relatively under-exploited., Methods and Scope: This review highlights the new non-oncologic applications of RGD-based tracers (with the focus on single-photon emission tomography and positron emission tomography). The focus is on the last 10 years of scientific literature (2009-2020). It is proposed that these imaging agents will be used for off-label indications that may provide options for disease monitoring where there are no approved tracers available, for instance Crohn's disease or osteoporosis. Fundamental science investigations have made progress in elucidating the involvement of integrin in various diseases not pertaining to oncology. Furthermore, RGD-based radiopharmaceuticals have been evaluated extensively for safety during clinical evaluations of various natures., Conclusion: Clinical translation of non-oncological applications for RGD-based radiopharmaceuticals and other imaging tracers without going through time-consuming extensive development is therefore highly plausible. Graphical 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 [ 68 Ga]Ga-PSMA-617 without losing its properties or causing toxicity. Following tolerated IV injections the capability of the microemulsion in altering [ 68 Ga]Ga-PSMA-617 distribution was presented at 120 min post injection based on its ex vivo biodistribution results.

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2 Mal , has been synthesized and studied for in vivo 64 Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1 Mal . The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [ 64 Cu]Cu-GluCAB-2 Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [ 64 Cu]Cu-GluCAB-2 Mal and previous-generation [ 64 Cu]Cu-GluCAB-1 Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [ 64 Cu]Cu-GluCAB-2 Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [ 64 Cu]Cu-Glu-CAB-2 Mal ., (© 2020 Wiley-VCH GmbH.)

Introduction: The compound named 4-[10-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanamido)decyl]-11-[10-(β,d-glucopyranos-1-yl)-1-oxodecyl]-1,4,8,11-tetraazacyclotetradecane-1,8-diacetic acid is a newly synthesised molecule capable of binding in vivo to albumin to form a bioconjugate. This compound was given the name, GluCAB(glucose-chelator-albumin-binder)-maleimide-1. Radiolabelled GluCAB-maleimide-1 and subsequent bioconjugate is proposed for prospective oncological applications and works on the theoretical dual-targeting principle of tumour localization through the "enhanced permeability and retention (EPR) effect" and glucose metabolism., Methods: The precursor, GluCAB-amine-2, and subsequent GluCAB-maleimide-1 was synthesised via sequential regioselective, distal N-functionalisation of a cyclam template with a tether containing a synthetically-derived β-glucoside followed by a second linker to incorporate a maleimide moiety for albumin-binding. GluCAB-amine-2 was radiolabelled with [ 64 Cu]CuCl 2 in 0.1 M NH 4 OAc (pH 3.5, 90 °C, 30 min), purified and converted post-labeling in 0.01 M PBS to [ 64 Cu]Cu-GluCAB-maleimide-1. Serum stability and protein binding studies were completed according to described methods. Healthy BALB/c ice (three groups of n = 5) were injected intravenously with [ 64 Cu]Cu-TETA, [ 64 Cu]Cu-GluCAB-amine-2 or [ 64 Cu]Cu-GluCAB-maleimide-1 and imaged using microPET/CT at 1, 2, 4, 8 and 24 h post-injection. Biodistribution of the compounds were determined ex vivo after 24 h using gamma counting., Results: GluCAB-maleimide-1 was synthesised in five consecutive steps with an overall yield of 11%. [ 64 Cu]Cu-GluCAB-amine-2 (97% labelling efficiency) was converted to [ 64 Cu]Cu-GluCAB-maleimide-1 (93% conversion; 90% radiochemical purity). Biodistribution analysis indicated that the control compounds were rapidly and almost completely excreted as compared to [ 64 Cu]Cu-GluCAB-maleimide-1 that exhibited a prolonged biological half-life (6-8 h). Both, [ 64 Cu]Cu-GluCAB-maleimide-1 and -amine-2 were excreted through the hepatobiliary system but a higher hepatic presence of the albumin-bound compound was noted. CONCLUSIONS, ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This initial evaluation paves the way for further investigation into the tumour targeting potential of [ 64 Cu]Cu-GluCAB-maleimide-1. An efficient targeted radioligand will allow for further development of a prospective theranostic agent for more personalized patient treatment which potentially improves overall patient prognosis, outcome and health care., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gallium-68 labelled 1,4,7-triazacyclononane-1,4,7-triacetic acid ubiquicidin (NOTA-UBI) is currently investigated as a PET radiopharmaceutical for the imaging of infections. The aim of this study was to compare the labelling characteristics of an optimized manual radiosynthesis method with those of optimized automated synthesis methods. Data from this study suggest that automated radiosynthesis of [ 68 Ga]Ga-NOTA-UBI provides a higher degree of robustness and repeatability than the manual method. Our results also suggest that for our full-scale automated synthesis, radical scavengers should be considered to reduce radiolysis. Automated synthesis methods have the advantage of markedly reducing radiation exposure to operators. Standardised automation also makes the synthesis more reliably compliant with Good Manufacturing Practice guidelines., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Prostate cancer (PCa) commonly metastasizes to the bones. There are several radionuclide techniques for imaging PCa skeletal metastases. We aimed to compare the lesion detection rate of [ 68 Ga]Ga-PSMA-11 PET/CT, [ 68 Ga]Ga-NODAGA-zoledronate ([ 68 Ga]Ga-NODAGA ZOL ) PET/CT, and [ 99m Tc]Tc-MDP bone scan in the assessment of bone metastases in patients with advanced PCa., Methods: We prospectively recruited two cohorts of patients (staging and re-staging cohorts) with advanced prostate cancer. The staging cohort was treatment-naïve PCa patients who showed skeletal metastases on bone scan. These patients were subsequently imaged with [ 68 Ga]Ga-PSMA-11 PET/CT and [ 68 Ga]Ga-NODAGA ZOL PET/CT. Re-staging cohort was patients who were previously treated with PSMA-based radioligand therapy and were experiencing PSA progression. The re-staging cohort was imaged with [ 68 Ga]Ga-PSMA-11 PET/CT and [ 68 Ga]Ga-NODAGA ZOL PET/CT. We performed a per-patient and per-lesion analysis of skeletal metastases in both cohorts and made a comparison between scan findings., Results: Eighteen patients were included with a median age of 68 years (range = 48-80) and a median Gleason score of 8. There were ten patients in the staging cohort with a median PSA of 119.26 ng/mL (range = 4.63-18,948.00) and eight patients in the re-staging cohort with a median PSA of 48.56 ng/mL (range = 6.51-3175.00). In the staging cohort, skeletal metastases detected by [ 68 Ga]Ga-PSMA-11 PET/CT, [ 68 Ga]Ga-NODAGA ZOL PET/CT, and bone scan were 322, 288, and 261, respectively, p = 0.578. In the re-staging cohort, [ 68 Ga]Ga-PSMA-11 PET/CT and [ 68 Ga]Ga-NODAGA ZOL PET/CT detected 152 and 191 skeletal metastases, respectively, p = 0.529. In two patients with negative [ 68 Ga]Ga-PSMA-11 PET/CT findings, [ 68 Ga]Ga-NODAGA ZOL detected one skeletal metastasis in one patient and 12 skeletal metastases in the other., Conclusion: In patients with advanced prostate cancer, [ 68 Ga]Ga-PSMA-11 PET/CT may detect more lesions than [ 68 Ga]Ga-NODAGA ZOL PET/CT and [ 99m Tc]Tc-MDP bone scan for the staging of skeletal metastases. In patients who experience PSA progression on PSMA-based radioligand therapy, [ 68 Ga]Ga-NODAGA PET/CT is a more suitable imaging modality for the detection of skeletal lesions not expressing PSMA. In the setting of re-staging, [ 68 Ga]Ga-NODAGA ZOL PET/CT may detect more lesions than [ 68 Ga]Ga-PSMA-11 PET/CT.

Cardiac and vascular infection is an arising cause of mortality and morbidity in the adult population. Diagnosis based on culture and anatomic imaging are frequently inconclusive. Radiolabeled leucocyte scintigraphy plays a useful role in the diagnosis and management of these serious infectious conditions. In this paper, we present an update on the diagnostic performance of single- photon emission tomographic (SPECT) techniques using different radionuclides in the management of patients with cardiac and vascular infections. We performed a thorough search of recent literature on the topic. We present a discussion on the clinical utility of different SPECT tracers in cardiac and vascular infections, including infective endocarditis, cardiac implantable electronic device (CIED) infections, left ventricular assist device infection, and vascular graft infection. Radionuclide technique using SPECT tracers is a useful imaging modality in the diagnosis of cardiac infection. Among the different SPECT tracers for infection imaging, radiolabeled leucocyte scintigraphy is currently the most useful tool in the diagnosis and management of patients with suspected cardiac and vascular infection. Radiolabeled leucocyte scintigraphy has a high specificity, a result of the ability of the leucocytes to accumulate as sites of pyogenic infection but not at sites of sterile inflammation such as seen in the early post-operative period or in response to the presence of a prosthetic cardiac or vascular material. Limited experience with radiotracers for in vivo labelling of leucocytes such as 99m Tc-sulesomab and 99m Tc-besilesomab show acceptable diagnostic performance without the need for the tedious process of ex-vivo labeling. 67 Ga scintigraphy used to be popular for cardiac and vascular infection imaging. Its use has run out of favor following the availability of more effective molecular imaging methods. SPECT techniques with radiolabeled leucocyte scintigraphy has a high diagnostic performance in the evaluation of patients with suspected cardiac or vascular infection. It is able to confirm or reject the presence of infection when results of anatomic imaging or culture remain inconclusive. Its diagnostic performance is not compromised by sterile inflammation occurring in the early post-operative period or in response to implanted prosthetic materials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The labeling of peptides with gallium-68 is often initially performed by manual labeling, but with high clinical demand, other alternatives are needed. Cold-kits or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [ 68 Ga]Ga-PSMA-11 production methods. Data from 40 kit-based and 40 automated syntheses of [ 68 Ga]Ga-PSMA-11 were analyzed. Pre-set criteria were evaluated including radiochemical purity, radionuclidic purity, chemical purity, physiological acceptability and sterility. The operator time and radiation dose received were measured. The robustness and repeatability of each method were assessed and a comparison of the running costs of each method is also provided. For both the methods all the analyzed products met the release criteria. No differences were found in radiochemical purity, radiochemical identity, radionuclidic purity, and sterility. However, radiochemical yield and apparent molar activity showed significant differences. For both methods, whole body radiation exposure to operators was lower than with manual labeling (25 - 40 μSv). The exposure during kit-based labeling (14.5 ± μSv) was seven times higher than that of automated synthesis (2.05 ± 0.99 μSv). The automated synthesis was the more expensive method. Both methods are sound alternatives to manual synthesis and offer higher quality, better radiation protection and a more reliable manufacturing of radiopharmaceuticals., (© 2020 John Wiley & Sons, Ltd.)

In this study, a significantly improved method for the synthesis of modular meso-BODIPY (boron dipyrromethene) derivatives possessing a free carboxylic acid group (which was subsequently coupled to peptides), is disclosed. This method provides a vastly efficient synthetic route with a > threefold higher overall yield than other reports. The resultant meso-BODIPY acid allowed for further easy incorporation into peptides. The meso-BODIPY peptides showed absorption maxima from 495-498 nm and emission maxima from 504-506 nm, molar absorptivity coefficients from 33 383-80 434 M-1 cm-1 and fluorescent quantum yields from 0.508-0.849. The meso-BODIPY-c(RGDyK) peptide was evaluated for plasma stability and (proved to be durable even up to 4 h) was then assessed for its fluorescence imaging applicability in vivo and ex vivo. The optical imaging in vivo was limited due to autofluorescence, however, the ex vivo tissue analysis displayed BODIPY-c(RGDyK) internalization and cancer detection thereby making it a novel tumor-integrin associated fluorescent probe while displaying the lack of interference the dye has on the properties of this ligand to bind the receptor.

Purpose: Nuclear imaging is an important preclinical research tool to study infectious diseases in vivo and could be extended to investigate complex aspects of malaria infections. As such, we report for the first time successful radiolabeling of a novel antibody specific to Plasmodium-infected erythrocytes (IIIB6), its in vitro assessment and molecular imaging in nude mice., Procedures: In vitro confocal microscopy was used to determine the stage-specificity of Plasmodium-infected erythrocytes recognised by IIIB6. To enable micro-positron emission tomography (PET)/X-ray computed tomography (CT) imaging, IIIB6 was conjugated to Bz-DFO-NCS and subsequently radiolabeled with zirconium-89. Healthy nude mice were injected with [ 89 Zr]IIIB6, and pharmacokinetics and organ uptake were monitored over 24 h. This was followed by post-mortem animal dissection to determine the biodistribution of [ 89 Zr]IIIB6., Results: IIIB6 recognised all the relevant stages of Plasmodium falciparum-infected erythrocytes (trophozoites, schizonts and gametocytes) that are responsible for severe malaria pathology. [ 89 Zr]IIIB6-radiolabeling yields were efficient at 84-89 %. Blood pool imaging analysis indicated a pharmacological half-life of 9.6 ± 2.5 h for [ 89 Zr]IIIB6. The highest standard uptake values were determined at 2-6 h in the liver followed by the spleen, kidneys, heart, stomach and lung, respectively. Minimal activity was present in muscle and bone tissues., Conclusion: In vitro characterization of IIIB6 and pharmacokinetic characterization of [ 89 Zr]IIIB6 revealed that this antibody has potential for future use in Plasmodium-infected mouse models to study malaria in a preclinical in vivo setting with PET/CT imaging.

This review describes the usefulness of in silico design approaches in the design of new radiopharmaceuticals, especially peptide-based radiotracers (including peptidomimetics). Although not part of the standard arsenal utilized during radiopharmaceutical design, the use of in silico strategies is steadily increasing in the field of radiochemistry as it contributes to a more rational and scientific approach. The development of new peptide-based radiopharmaceuticals as well as a short introduction to suitable computational approaches are provided in this review. The first section comprises a concise overview of the three most useful computeraided drug design strategies used, namely i) a Ligand-based Approach (LBDD) using pharmacophore modelling, ii) a Structure-based Design Approach (SBDD) using molecular docking strategies and iii) Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) predictions. The second section summarizes the challenges connected to these computer-aided techniques and discusses successful applications of in silico radiopharmaceutical design in peptide-based radiopharmaceutical development, thereby improving the clinical procedure in Nuclear Medicine. Finally, the advances and future potential of in silico modelling as a design strategy is highlighted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)