A Precise Prediction of the Chemical and Thermal Shrinkage during Curing of an Epoxy Resin.

A precise prediction of the cure-induced shrinkage of an epoxy resin is performed using a finite element simulation procedure for the material behaviour. A series of experiments investigating the cure shrinkage of the resin system has shown a variation in the measured cure-induced strains. The observed variation results from the thermal history during the pre-cure. A proposed complex thermal expansion model and a conventional chemical shrinkage model are utilised to predict the cure shrinkage observed with finite element simulations. The thermal expansion model is fitted to measured data and considers material effects such as the glass transition temperature and the evolution of the expansion with the degree of cure. The simulations accurately capture the exothermal heat release from the resin and the cure-induced strains across various temperature profiles. The simulations follow the experimentally observed behaviour. The simulation predictions achieve good accuracy with 2-6% discrepancy compared with the experimentally measured shrinkage over a wide range of cure profiles. Demonstrating that the proposed complex thermal expansion model affects the potential to minimise the shrinkage of the studied epoxy resin. A recommendation of material parameters necessary to accurately determine cure shrinkage is listed. These parameters are required to predict cure shrinkage, allow for possible minimisation, and optimise cure profiles for the investigated resin system. Furthermore, in a study where the resin movement is restrained and therefore able to build up residual stresses, these parameters can describe the cure contribution of the residual stresses in a component.

Burden of non-motor symptoms of Parkinson's disease: cost-of-illness and quality-of-life estimates through a scoping review.

INTRODUCTION: Parkinson's Disease (PD) is a progressive, chronic neurodegenerative disease, representing significant economic and social burdens. It is typically defined by motor symptoms (MSs), however, this does not reflect the full patient burden. Non-motor symptoms (NMSs) are increasingly recognized as central characteristics of PD. However, they still lack recognition in research. Therefore, this study aims to identify relevant NMSs, their prevalence, and the effect they have on Quality-of-Life (QoL) and Cost-of-Illness (COI). Secondly, it aims to identify gaps in the current body of knowledge and propose possible ways future research could bridge those gaps. METHODS: The study employed a scoping review, identifying 60 records for inclusion, using PubMed and Web of Science. It included studies from Spain or Italy, including data on People with Parkinson's Disease. A comparative analysis was performed using Microsoft Excel. RESULTS: It showed that the body of evidence relevant to NMSs, their prevalence, QoL, and COI is limited, or that estimates vary to an extent where interpretation is difficult. CONCLUSION: Most studies suffer from generalization, representation, and standardization issues, stemming from their designs and methodological decisions. Although the findings of this study should be interpreted with caution, several recommendations are made for future research.

Investigation of imaging the somatostatin receptor by opening the blood-brain barrier with melittin - A feasibility study using positron emission tomography and [64Cu]Cu-DOTATATE.

DOTATATE is a somatostatin peptide analog used in the clinic to detect somatostatin receptors which are highly expressed on neuroendocrine tumors. Somatostatin receptors are found naturally in the intestines, pancreas, lungs, and brain (mainly cortex). In vivo measurement of the somatostatin receptors in the cortex has been challenging because available tracers cannot cross the blood-brain barrier (BBB) due to their intrinsic polarity. A peptide called melittin, a main component of honeybee venom, has been shown to disrupt plasma membranes and increase the permeability of biological membranes. In this study, we assessed the feasibility of using melittin to facilitate the passage of [64Cu]Cu-DOTATATE through the BBB and its binding to somatostatin receptors in the cortex. Evaluation included in vitro autoradiography on Long Evans rat brains to estimate the binding affinity of [64Cu]Cu-DOTATATE to the somatostatin receptors in the cortex and an in vivo evaluation of [64Cu]Cu-DOTATATE binding in NMRI mice after injection of melittin. This study found an in vitro Bmax = 89 ± 4 nM and KD = 4.5 ± 0.6 nM in the cortex, resulting in a theoretical binding potential (BP) calculated as Bmax/KD ≈ 20, which is believed suitable for in vivo brain PET imaging. However, the in vivo results showed no significant difference between the control and melittin injected mice, indicating that the honeybee venom failed to open the BBB. Additional experiments, potentially involving faster injection rates are required to verify that melittin can increase brain uptake of non-BBB permeable PET tracers. Furthermore, an evaluation of whether a venom with a narrow therapeutic range can be used for clinical purposes needs to be considered.

Tailored cure profiles for simultaneous reduction of the cure time and shrinkage of an epoxy thermoset.

Defining the specific cure profile of thermosetting polymers is an important aspect in many applications where the mechanical performance and appearance of components can be affected. Cure-induced strains or stresses from the shrinkage of thermosets lead to reduced performance due to accelerated damage or discarded products due to distortions. This research focuses on validating a proposed modelling framework, simulating the load-transferring part of the curing process affecting the mechanical performance. The model's accuracy is evaluated against experimental results, and the model prediction is found to be within an accuracy of 2-8% of the experimental results. A 16-hour and 31-hour two-stage cure profile was compared and validated experimentally. The short profile results in a higher cure-induced of -0.56% with the longer profile yielding -0.46% cure-induced strain. Based on the model, a new three-stage cure profile has been proposed. Using this, it is possible to achieve a low level of cure-induced strain of -0.45% at a shorter cure time on 18 h.

Targeted imaging of uPAR expression in vivo with cyclic AE105 variants.

A comprehensive literature reports on the correlation between elevated levels of urokinase-type plasminogen activator receptor (uPAR) and the severity of diseases with chronic inflammation including solid cancers. Molecular imaging is widely used as a non-invasive method to locate disease dissemination via full body scans and to stratify patients for targeted treatment. To date, the only imaging probe targeting uPAR that has reached clinical phase-II testing relies on a high-affinity 9-mer peptide (AE105), and several studies by positron emission tomography (PET) scanning or near-infra red (NIR) fluorescence imaging have validated its utility and specificity in vivo. While our previous studies focused on applying various reporter groups, the current study aims to improve uPAR-targeting properties of AE105. We successfully stabilized the small uPAR-targeting core of AE105 by constraining its conformational landscape by disulfide-mediated cyclization. Importantly, this modification mitigated the penalty on uPAR-affinity typically observed after conjugation to macrocyclic chelators. Cyclization did not impair tumor targeting efficiency of AE105 in vivo as assessed by PET imaging and a trend towards increased tracer uptake was observed. In future studies, we predict that this knowledge will aid development of new fluorescent AE105 derivatives with a view to optical imaging of uPAR to assist precision guided cancer surgery.

A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.

Adenocarcinoma in situ (ductal type) ex pleomorphic adenoma of the lacrimal gland.

Purpose: To present the clinical and histopathological characteristics of a rare case of ductal carcinoma in situ ex pleomorphic adenoma in the lacrimal gland. Observations: A 73-years-old Caucasian female presented with complaints of double vision and pain in the left eye region. Clinical examination revealed ptosis and exophthalmos of the left eye as well as diplopia on downward gaze. Magnetic resonance imaging of the left orbit demonstrated a 17 × 22 mm homogeneous tumor in the left lacrimal fossa. The tumor was excised in toto. Histopathological examination revealed a pleomorphic adenoma with ductal structures with benign looking epithelial cells, surrounded by myoepithelial cells. Tumor areas with cribriform architecture consisting of ductal structures with abnormal luminal epithelial cells and intact myoepithelial cell layer were also present. The surgical margins were clear. All luminal and myoepithelial cells were positive for cytokeratin 7, the luminal cells in the cribriform areas were positive for human epidermal growth factor 2 and androgen receptor. The myoepithelial cells were positive for cytokeratin 5, calponin and focally for glial fibrillar acid protein. The findings were diagnostic for ductal carcinoma in situ ex pleomorphic adenoma. Next generation sequencing Oncomine Comprehensive Assay mutation analysis found mutations in the BRCA2 (p.K3326*), BAP1 (p.S395*), and TP53 (p.E285K) genes in the ductal carcinoma in situ and BRCA2 (p.C9976A) in the pleomorphic adenoma part. Conclusion and importance: To our knowledge, this tumor is only the second described ductal carcinoma in situ ex pleomorphic adenoma of the lacrimal gland.

Neoadjuvant Gold Nanoshell-Based Photothermal Therapy Combined with Liposomal Doxorubicin in a Mouse Model of Colorectal Cancer.

Introduction: Traditional cancer treatments, such as chemotherapy, are often incapable of achieving complete responses as standalone therapies. Hence, current treatment strategies typically rely on a combination of several approaches. Nanoparticle-based photothermal therapy (PTT) is a technique used to kill cancer cells through localized, severe hyperthermia that has shown promise as an add-on treatment to multiple cancer therapies. Here, we evaluated whether the combination of gold nanoshell (NS)-based PTT and liposomal doxorubicin could improve outcome in a mouse model of colorectal cancer. Methods: First, NS-based PTT was performed on tumor-bearing mice. Radiolabeled liposomes were then injected at different timepoints to follow their accumulation in the tumor and determine the ideal injection time after PTT. In addition, fluorescent liposomes were used to observe the liposomal distribution in the tumor after PTT. Finally, we combined PTT and doxorubicin-loaded liposomes and studied the effect of the treatment strategy on the mice by following tumor growth and survival. Results: PTT significantly improved liposomal accumulation in the tumor, but only when the liposomes were injected immediately after the therapy. The liposomes accumulated mostly in regions adjacent to the ablated areas. When PTT was combined with liposomal doxorubicin, the mice experienced a slowdown in tumor growth and an improvement in survival. Conclusion: According to our preclinical study, NS-based PTT seems promising as an add-on treatment for liposomal chemotherapy and potentially other systemic therapies, and could be relevant for future application in a clinical setting.

Synthesis and in vivo evaluation of [11C]tucatinib for HER2-targeted PET imaging.

Tucatinib is a selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) in April 2020 for HER2-positive lesions in metastatic breast cancer patients, including CNS metastases. In this article, we attempted to develop the first small molecule, blood-brain-barrier (BBB) penetrant HER2 PET imaging probe based on tucatinib. [11C]tucatinib was synthesized via a Stille-coupling from the respective trimethylstannyl precursor and its biodistribution was evaluated in NMRI nude mice bearing HER2-overexpressing human ovarian cancer cells (SKOV-3). No significant tumor accumulation was observed despite its high affinity for HER-2 receptors (IC50 = 6.9 nM). High liver and intestinal uptake indicate that [11C]tucatinib is too lipophilic to be used as a tumor targeting PET tracer. Therefore, chemical modifications of [11C]tucatinib are needed to increase the polarity for tumor imaging. Tucatinib as an FDA approved drug is still an interesting platform to develop the first small molecule HER2-selective PET tracer. The study highlights the differences between a drug, which needs to be effective, and an imaging agent, which is dependent on contrast.

Synthesis and radiolabeling of a polar [125 I]I-1,2,4,5-tetrazine.

Pretargeting imaging has gained a lot of prominence, due to its excellent bioorthogonality and improved imaging contrast compared to conventional imaging. A new iodo tetrazine (Tz) derivative has been synthesized and further developed into the corresponding iodine-125 (125 I) analog (12), via the trimethylstannane precursor. Radiolabeling with either N-chlorosuccinimide or chloramine-T, in either MeCN or MeOH proceeded with a radiochemical conversion (RCC) of >80%. Subsequent deprotection only proved successful, among the tested conditions, when the radiolabeled Tz was stirred in 6-M HCl(aq.) at 60°C for 2.5 h. To the best of our knowledge, this is the first H-tetrazine labeled with iodine. In vivo investigations on the pretargeting ability of 12 are currently under way.

Bioorthogonal Click of Colloidal Gold Nanoparticles to Antibodies In vivo.

Combining nanotechnology and bioorthogonal chemistry for theranostic strategies offers the possibility to develop next generation nanomedicines. These materials are thought to increase therapeutic outcome and improve current cancer management. Due to their size, nanomedicines target tumors passively. Thus, they can be used for drug delivery purposes. Bioorthogonal chemistry allows for a pretargeting approach. Higher target-to-background drug accumulation ratios can be achieved. Pretargeting can also be used to induce internalization processes or trigger controlled drug release. Colloidal gold nanoparticles (AuNPs) have attracted widespread interest as drug delivery vectors within the last decades. Here, we demonstrate for the first time the possibility to successfully ligate AuNPs in vivo to pretargeted monoclonal antibodies. We believe that this possibility will facilitate the development of AuNPs for clinical use and ultimately, improve state-of-the-art patient care.

Combination of [177Lu]Lu-DOTA-TATE Targeted Radionuclide Therapy and Photothermal Therapy as a Promising Approach for Cancer Treatment: In Vivo Studies in a Human Xenograft Mouse Model.

Peptide receptor radionuclide therapy (PRRT) relies on α- and ß-emitting radionuclides bound to a peptide that commonly targets somatostatin receptors (SSTRs) for the localized killing of tumors through ionizing radiation. A Lutetium-177 (177Lu)-based probe linked to the somatostatin analog octreotate ([177Lu]Lu-DOTA-TATE) is approved for the treatment of certain SSTR-expressing tumors and has been shown to improve survival. However, a limiting factor of PRRT is the potential toxicity derived from the high doses needed to kill the tumor. This could be circumvented by combining PRRT with other treatments for an enhanced anti-tumor effect. Photothermal therapy (PTT) relies on nanoparticle-induced hyperthermia for cancer treatment and could be a useful add-on to PRRT. Here, we investigate a strategy combining [177Lu]Lu-DOTA-TATE PRRT and nanoshell (NS)-based PTT for the treatment of SSTR-expressing small-cell lung tumors in mice. Our results showed that the combination treatment improved survival compared to PRRT alone, but only when PTT was performed one day after [177Lu]Lu-DOTA-TATE injection (one of the timepoints examined), showcasing the effect of treatment timing in relation to outcome. Furthermore, the combination treatment was well-tolerated in the mice. This indicates that strategies involving NS-based PTT as an add-on to PRRT could be promising and should be investigated further.

Development of 18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging.

Pretargeted PET imaging is an emerging and fast-developing method to monitor immuno-oncology strategies. Currently, tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a method to 18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetrazines-one of the most promising structures for in vivo pretargeted applications-were inaccessible using this strategy. We believed that our successful efforts to 18F-label H-tetrazines using low basic labeling conditions could also be used to label bispyridyl tetrazines via aliphatic nucleophilic substitution. Here, we report the first direct 18F-labeling of bispyridyl tetrazines, their optimization for in vivo use, as well as their successful application in pretargeted PET imaging. This strategy resulted in the design of [18F]45, which could be labeled in a satisfactorily radiochemical yield (RCY = 16%), molar activity (Am = 57 GBq/µmol), and high radiochemical purity (RCP > 98%). The [18F]45 displayed a target-to-background ratio comparable to previously successfully applied tracers for pretargeted imaging. This study showed that bispyridyl tetrazines can be developed into pretargeted imaging agents. These structures allow an easy chemical modification of 18F-labeled tetrazines, paving the road toward highly functionalized pretargeting tools. Moreover, bispyridyl tetrazines led to near-instant drug release of iTCO-tetrazine-based 'click-to-release' reactions. Consequently, 18F-labeled bispyridyl tetrazines bear the possibility to quantify such release in vivo in the future.

Photothermal Therapy as Adjuvant to Surgery in an Orthotopic Mouse Model of Human Fibrosarcoma.

Surgery is still the first-line treatment for multiple solid cancers. However, recurrence is a common issue, especially when dealing with aggressive tumors or tumors that are difficult to completely remove due to their location. Getting clear surgical margins can be challenging, but treatment strategies combining surgery with other anti-cancer therapies can potentially improve the outcome. Photothermal therapy (PTT) is a technique that relies on photoabsorbing agents, such as gold nanoparticles, to transform light into local hyperthermia. This technique can be used to ablate tumor tissue where the photoabsorbing agent accumulates, sparing healthy surrounding tissue. In this study, we examined the potential of gold nanoparticle-based PTT as an adjuvant treatment to surgery in a mouse model of human fibrosarcoma. For this we performed subtotal tumor resection to mimic a clinical situation where total tumor removal is not achieved, and subsequent PTT was applied on the surgical field. Our results showed that animals undergoing adjuvant PTT after surgery presented sustained delayed tumor growth and improved survival when compared to animals that only underwent surgery. We believe that these findings show the potential of PTT as an adjuvant method to traditional tumor surgery and could pave way to more personalized treatment options.

Direct Cu-mediated aromatic 18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging.

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct 18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct 18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated 18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY of ca. 10%, with a molar activity of 134 ± 22 GBq µmol-1 and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.

Development of the First Aliphatic 18F-Labeled Tetrazine Suitable for Pretargeted PET Imaging-Expanding the Bioorthogonal Tool Box.

Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the state-of-art choice for in vivo chemistry. We have recently identified key properties for tetrazines in pretargeting. We have also developed a method to 18F-label reactive tetrazines using an aliphatic nucleophilic substitution strategy. Here, we combined this knowledge and developed an 18F-labeled tetrazine for pretargeted imaging. In order to develop this ligand, a small SAR study was performed. The most promising compound was selected for labeling and subsequent positron-emission-tomography in vivo imaging. Radiolabeling was achieved in satisfactory yields, molar activities, and high radiochemical purities. [18F]15 displayed favorable pharmacokinetics and remarkable target-to-background ratios-as early as 1 h post injection. We believe that this agent could be a promising candidate for translation into clinical studies.

The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma.

The development of tumor-targeted probes that can efficiently reach cancerous tissue is an important focus of preclinical research. Photothermal cancer therapy (PTT) relies on light-absorbing molecules, which are directed towards tumor tissue and irradiated with an external source of light. This light is transformed into heat, causing localized hyperthermia and tumor death. The fluorescent probe indocyanine green (ICG) is already used as an imaging agent both preclinically and in clinical settings, but its use for PTT is yet to be fully exploited due to its short retention time and non-specific tumor targeting. Therefore, increasing ICG tumor uptake is necessary to improve treatment outcome. The urokinase-type plasminogen activator receptor, uPAR, is overexpressed in multiple tumor types. ICG-Glu-Glu-AE105, consisting of the uPAR-targeting peptide AE105 conjugated to ICG, has shown great potential for fluorescence-guided surgery. In this study, ICG-Glu-Glu-AE105 was evaluated as photothermal agent in a subcutaneous mouse model of human glioblastoma. We observed that the photothermal abilities of ICG-Glu-Glu-AE105 triggered high temperatures in the tumor during PTT, leading to tumor death and prolonged survival. This confirms the potential of ICG-Glu-Glu-AE105 as photothermal agent and indicates that it could be used as an add-on to the application of the probe for fluorescence-guided surgery.

Lipophilicity and Click Reactivity Determine the Performance of Bioorthogonal Tetrazine Tools in Pretargeted In Vivo Chemistry.

The development of highly selective and fast biocompatible reactions for ligation and cleavage has paved the way for new diagnostic and therapeutic applications of pretargeted in vivo chemistry. The concept of bioorthogonal pretargeting has attracted considerable interest, in particular for the targeted delivery of radionuclides and drugs. In nuclear medicine, pretargeting can provide increased target-to-background ratios at early time-points compared to traditional approaches. This reduces the radiation burden to healthy tissue and, depending on the selected radionuclide, enables better imaging contrast or higher therapeutic efficiency. Moreover, bioorthogonally triggered cleavage of pretargeted antibody-drug conjugates represents an emerging strategy to achieve controlled release and locally increased drug concentrations. The toolbox of bioorthogonal reactions has significantly expanded in the past decade, with the tetrazine ligation being the fastest and one of the most versatile in vivo chemistries. Progress in the field, however, relies heavily on the development and evaluation of (radio)labeled compounds, preventing the use of compound libraries for systematic studies. The rational design of tetrazine probes and triggers has thus been impeded by the limited understanding of the impact of structural parameters on the in vivo ligation performance. In this work, we describe the development of a pretargeted blocking assay that allows for the investigation of the in vivo fate of a structurally diverse library of 45 unlabeled tetrazines and their capability to reach and react with pretargeted trans-cyclooctene (TCO)-modified antibodies in tumor-bearing mice. This study enabled us to assess the correlation of click reactivity and lipophilicity of tetrazines with their in vivo performance. In particular, high rate constants (>50 000 M-1 s-1) for the reaction with TCO and low calculated logD 7.4 values (below -3) of the tetrazine were identified as strong indicators for successful pretargeting. Radiolabeling gave access to a set of selected 18F-labeled tetrazines, including highly reactive scaffolds, which were used in pretargeted PET imaging studies to confirm the results from the blocking study. These insights thus enable the rational design of tetrazine probes for in vivo application and will thereby assist the clinical translation of bioorthogonal pretargeting.

The use of innovative payment mechanisms for gene therapies in Europe and the USA.

Innovative reimbursement mechanisms have long been considered potential solutions to the data uncertainty associated with one-off, high-value gene therapies that have long-term therapeutic potential, combined with limited supporting evidence at launch. The launches of increasing numbers of such gene therapies in Europe and the USA in the past 5 years provide valuable exemplars of how innovative reimbursement mechanisms are used by healthcare system decision makers in practice. This review details the use of such reimbursement schemes for recently launched gene therapies in key European countries and the USA, and shows that they are more widespread in Europe than in the USA. Although innovative payment schemes are increasingly used across countries, differences in healthcare system structures (e.g., single- vs multi-payer systems) and willingness to pay mean that decision makers in different countries have different incentives to manage uncertainties around long-term, real-world product value.

Evaluation of [64Cu]Cu-NOTA-PEG7-H-Tz for Pretargeted Imaging in LS174T Xenografts-Comparison to [111In]In-DOTA-PEG11-BisPy-Tz.

Pretargeted nuclear imaging for the diagnosis of various cancers is an emerging and fast developing field. The tetrazine ligation is currently considered the most promising reaction in this respect. Monoclonal antibodies are often the preferred choice as pretargeting vector due to their outstanding targeting properties. In this work, we evaluated the performance of [64Cu]Cu-NOTA-PEG7-H-Tz using a setup we previously used for [111In]In-DOTA-PEG11-BisPy-Tz, thereby allowing for comparison of the performance of these two promising pretargeting imaging agents. The evaluation included a comparison of the physicochemical properties of the compounds and their performance in an ex vivo blocking assay. Finally, [64Cu]Cu-NOTA-PEG7-H-Tz was evaluated in a pretargeted imaging study and compared to [111In]In-DOTA-PEG11-BisPy-Tz. Despite minor differences, this study indicated that both evaluated tetrazines are equally suited for pretargeted imaging.