High Uptake Research Articles

A hybrid [18F]fluoropivalate PET-multiparametric MRI to detect and characterise brain tumour metastases based on a permissive environment for monocarboxylate transport.

The incidence of Intracranial Metastatic Disease (IMD) continues to increase in part due to improvements in systemic therapy resulting in durable control of extra-cranial disease (ECD). Contrast-enhanced Magnetic Resonance Imaging (CE-MRI) is the preferred method for imaging IMD, but has limitations particularly in follow-up surveillance scans to optimise patient care. We investigate a new diagnostic approach of hybrid ([18]F]fluoropivalate (FPIA) Positron Emission Tomography-multiparametric MRI (PET-mpMRI), in 12 treatment-naïve and 10 stereotactic radiosurgery (SRS)-treated patients (± combination therapy within 4-8 weeks). High FPIA uptake was seen in all IMD compared to contralateral white matter, regardless of ECD tumour-of-origin (p = 0.0001) and FPIA-PET volumes extended beyond CE-MRI volumes in treatment-naïve but not SRS-treated tumours. Patients with maximum PET Standardised Uptake Value, (SUVmax) ≥ 2.0 showed particularly short overall-survival (median 4 v 15 months, p = 0.0136), while CE-MRI was uninformative regarding outcome; a PET-mpMRI grade-measure also provided non-invasive prediction of overall-survival, warranting larger studies of PET-mpMRI. Independent metabolomics analyses were consistent with shared adaptation of IMD to utilise or accumulate monocarboxylates and acylcarnitines, respectively, providing a common phenotypic basis to FPIA-PET. Reprogrammed monocarboxylate metabolism-related FPIA-PET provides new insights into annotating IMD, to be expounded in future opportunities for therapy decisions for the growing number of cancer patients with IMD [Trial registration reference: Clinicaltrials.gov NCT04807582; 3rd November 2021, retrospectively registered].

Enhancing CO2 Capture Via Fast Microwave-Assisted Synthesis of the CALF-20 Metal-Organic Framework.

Metal-organic frameworks (MOFs) are promising porous materials for CO2 adsorption due to their high surface area, tunable properties, and selective adsorption capabilities. The recently reported Calgary Framework 20 (CALF-20) MOF has very appealing CO2 capture properties: high uptake capacity; low regeneration energy; durability (>450 000 cycles) under steam and wet acid gases; simple and scalable synthesis. This study investigates the microwave (MW)-assisted synthesis of CALF-20, which reduces reaction time 12-fold while enhancing the synthesis yield to 97%. Structural analysis confirmed that MW-synthesized CALF-20 retains its crystallographic structure and shows improved CO2 capture performance, exhibiting higher adsorption capacity (∼20% higher), selectivity, and lower regeneration energy. This method provides a rapid and efficient alternative for producing the CALF-20 adsorbent for CO2 capture and separation applications.

Knowledge and Attitudes Regarding Respiratory Syncytial Virus (RSV) Prevention: A Systematic Review

Background: New strategies for respiratory syncytial virus (RSV) prevention are available and are in development, but their acceptance is crucial to their effectiveness. Objectives: This systematic review aims to summarize current quantitative and qualitative evidence regarding knowledge and attitudes relating to RSV prevention. Methods: Six databases (PubMed, Scopus, APA PsycArticles; APA PsycInfo; CINAHL Complete; Psychology and Behavioral Sciences Collection) and two preprint repositories (medRxiv and Preprints) were searched up until 23 December 2024 (PROSPERO: CRD42024602351). Results: Sixty-one articles were included, focusing on vaccination for the elderly and adults at risk (n = 10) or pregnant people (n = 24, of which 8 also examined preferences for maternal vs. infant immunization) and infant immunization (n = 27, of which 16 focused on palivizumab, with 6 focusing on adherence to its monthly administration). Eighteen articles assessed attitudes in healthcare professionals. Overall, findings showed limited knowledge and awareness of RSV but generally positive attitudes towards prevention strategies and moderate to high intentions and uptake rates. Protection against the disease and perceived severity promoted acceptance, whereas concerns about side effects hindered it. Maternal vaccination was more acceptable than infant immunization. Conclusions: Attitudes towards RSV prevention options were generally favorable. Should more options become available, preferences may depend on which options are available, their characteristics, and how they are framed and presented. These insights highlight the importance of education on RSV grounded in decision-making literature, while recognizing the likely favorable reception of preventive measures across target age-populations.

Unveiling the potential of copper-61 vs. gallium-68 for SSTR PET imaging.

In recent years, copper-61 has attracted considerable attention from both physicists and radiochemists due to its favorable physical decay properties for PET imaging and its ease of production at any cyclotron center producing [18F]FDG. The aim of this study was to evaluate the potential of 61Cu-based radiopharmaceuticals for PET imaging of NETs, as an alternative to the commonly used gallium-68. Copper-61 was produced by irradiation of natural zinc liquid targets, followed by post-processing. In vitro evaluation of 61Cu- and 68Ga-labeled SST analogues was performed in SSTR positive AR42J tumor cells. PET/MRI was carried out in mice bearing AR42J subcutaneous tumors. High molar activity [61Cu]Cu-DOTA-TATE and [61Cu]Cu-NOTA-TATE were successfully prepared with a radiochemical purity of over 95% and were shown to be stable for at least 6h after the EOS. Both 61Cu- and 68Ga-labeled SST analogues exhibited high cellular uptake, with residual uptake when blocked with an excessive amount of peptide precursor. [61Cu]Cu-NOTA-TATE showed the highest tumor uptake at 1h p.i. (13.25 ± 1.86%ID/g) and the tumor-to-non-tumor ratio increased from 1h to 4h p.i. At the later time point, tumor visualization improved compared to 1h p.i. Moreover, preclinical PET/MR images demonstrated that [61Cu]Cu-NOTA-TATE has a more favorable biodistribution and imaging properties than [61Cu]Cu-DOTA-TATE, with the extended PET imaging window providing a clear advantage of [61Cu]Cu-NOTA-TATE over its gallium-68 analogues. [61Cu]Cu-NOTA-TATE showed similar biodistribution and pharmacokinetics to [68Ga]Ga-DOTA-TATE at 1h p.i., while demonstrating superior imaging characteristics for late PET imaging. These findings demonstrate that [61Cu]Cu-NOTA-TATE holds promising characteristics for improving the detection of NETs with increased translational potential.

COVID-19 vaccine uptake in Zimbabwe and Sierra Leone: an application of Health Belief Model constructs.

While African countries, in general, experienced a milder COVID-19 impact compared to Western nations, they faced challenges with vaccine uptake. Specifically, Zimbabwe and Sierra Leone saw vaccine acceptance rates below global averages. This research delves into the underlying factors that influenced these disparities in vaccine acceptance in these two countries, using the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) as guiding frameworks. This study utilized data from a cross-sectional survey encompassing 2,312 participants from areas where the Africa Christian Health Associations Platform (ACHAP) operates in Zimbabwe and Sierra Leone. The survey assessed respondents' views in line with core HBM and TPB constructs, in addition to their levels of vaccine acceptance. We then employed adjusted logistic regression models to investigate the correlation between health behavior change theory constructs and vaccine uptake, taking into account variables like gender, age, education, and country of residence. Several associations were identified, including high vaccine uptake correlated with a heightened perceived threat of COVID-19 (OR = 2.674; p < .001), recognized benefits of vaccination (OR = 1.482; p < .001), stronger perceived behavior control (OR = 2.189; p < .001), and fewer perceived barriers to vaccination (OR = 0.173; p < .001). Conversely, low vaccine uptake was linked to diminished perceived threats (OR = 0.540; p < .001), fewer perceived benefits (OR = 0.762; p < .001), weaker perceived behavior control (OR = 0.429; p < .001), and heightened perceptions of barriers (OR = 2.001; p < .001). Results underscore the significance and utility of theoretical constructs in understanding variations in vaccine uptake levels. They highlight the importance of relying on well-established theories to grasp decision-making mechanisms and to shape suggestions for behavior modification. Consequently, to boost vaccine acceptance, public health campaigns should focus on reshaping risk perceptions, addressing obstacles, emphasizing the advantages of getting vaccinated, and fostering a sense of self-efficacy within target communities.

Discovery of Fatty Acid Translocase CD36-Targeting Near-Infrared Fluorescent Probe Enables Visualization and Imaging-Guided Surgery for Glioma.

Despite therapeutic advances in glioma, glioma-related mortality rates remain high due to its extremely poor prognosis and high recurrence. Near-infrared (NIR) fluorescence imaging technologies, using the clinically approved fluorescent probe 5-ALA, have gained prominence in facilitating visualization of glioma resection. However, the false-positive and false-negative results of 5-ALA decrease its sensitivity and specificity in detecting glioma, thereby hampering its use in glioma surgical navigation. Herein, a novel molecular probe MPA-Pip-abt-510 labeled with a NIR fluorescent dye MPA was developed, and its ability to target the CD36 protein, which is upregulated in glioma, was assessed. Fluorescent-labeled probes, conjugated to the CD36-targeting ligand abt-510, demonstrated high specificity and selectivity for CD36-positive tumor cells in vitro and tumor tissue in vivo. Biodistribution analysis of MPA-Pip-abt-510 revealed high tumor-specific accumulation in tumors, accompanied by minimal nonspecific uptake in background tissues, yielding a signal-to-noise ratio (SNR) of 6.6 ± 0.4 in a U87 subcutaneous glioma model 10 h postinjection. Meanwhile, quantitative analysis validated the high uptake of MPA-Pip-abt-510 in the U87 orthotopic tumor model, with a tumor-to-brain SNR of 5.4 ± 0.5, enabling the accurate identification of tumor tissue for surgical navigation. Moreover, pathological analysis of tumor and healthy brain tissues unveiled well-defined tumor boundaries, highlighting the capacity of the MPA-Pip-abt-510 probe to precisely visualize the CD36 protein at the molecular level. Given its rapid tumor-targeting abilities, durable retention, and accurate outlining of tumor boundaries, MPA-Pip-abt-510 emerges as a promising CD36-targeted fluorescence contrast agent and expands the toolbox of glioma fluorescent probes for surgical navigation.

Synthesis and characterization of L-Arg-polypyrrole@g-C3N4 nanocomposite for highly efficient removal of orange G dye: Mechanistic insights and RSM@BBD optimization

Dye pollution, specifically orange G dye (OG dye) has been substantial threat owing to its poisonous to both human health and ecosystems. Thus, developing adsorbents with high stability, strong adsorption efficiency, easy separation, and excellent regenerability remains a challenge. In the present research, L-Arg-PPy@g-C3N4 nanocomposite was crafted through an interfacial polymerization process. OG adsorption onto L-Arg-PPy@g-C3N4 was optimized in batch mode using response surface methodology coupled with box-Behnken design (RSM@BBD) to assess the adsorbent dose, pH and initial OG concentration. The developed composite proficiently eliminates 94.87 % of OG dye molecules at 1 g·L−1 with a reaction time approaching 60 min, with high uptake efficacy of 23.31 mg·g−1. The Langmuir isotherm and pseudo-second-order kinetic models effectively describe the adsorption process in both aqueous solution and wastewater. Based on XPS/FT-IR analysis, the OG dye mechanism is mainly driven by π-π interactions, hydrogen bonding and electrostatic attractions. The adsorbent efficacy achieved 88.3 % removal in real wastewater treatment. This slight detriment was explained by the individual study of co-interfering ions. Reusability tests confirmed the adsorbent’s excellent regeneration capability for purifying wastewater containing OG dye molecules maintaining 73.8 % removal capacity during 4 cycles. These findings confirm the potential of the developed L-Arg-PPy@g-C3N4 as an effective filter for OG removal from wastewater.

Role of [99mTc]Tc-DPD gated-SPECT-CT in the assessment of myocardial uptake patterns in transthyretin amyloidosis (TTR-CA).

To evaluate the feasibility of identifying various distribution patterns of [99mTc]Tc-DPD in patients with cardiac transthyretin amyloidosis using gated SPECT-CT. Gated SPECT-CT was performed in patients with a positive scintigraphy result for cardiac amyloidosis due to transthyretin (TTR-CA). Patients were categorized into several groups based on sex, degree of radiopharmaceutical uptake according to the Perugini's visual scale and ventricular ejection fraction (LVEF). Cardiac polar maps were obtained using Emory Cardiac Toolbox™ software and scored by segments according to radiopharmaceutical uptake on a scale from 0 (no uptake) to 4 (very high uptake intensity). The Mann-Whitney U and Pearson's Chi-square statistical tests were employed to identify significant differences in distribution patterns according to the different variables under study. 65 patients were evaluated. The gender variable determined the main statistically significant differences, highlighting distinct distribution patterns of the radiopharmaceutical at the cardiac level: while women showed lower accumulation of [99mTc]Tc-DPD in the middle anterior (p = 0.035) and basal anterior (p = 0.001) segments, whereas men demonstrated higher accumulation in the basal anteroseptal (p = 0.009) and basal inferoseptal (p = 0.009) segments, and lower scores in the lateroapical segment (p = 0.039). Gated SPECT-CT is an essential tool for assessing the distribution pattern of [99mTc]Tc-DPD of patients with TTR-CA, offering valuable insights into the pathophysiology of the disease.

The N-acetyltransferase 10 inhibitor [11C]remodelin: synthesis and preliminary positron emission tomography study in mice

Background4-(4-Cyanophenyl)-2-(2-cyclopentylidenehydrazinyl)thiazole (remodelin) is a potent N-acetyltransferase 10 (NAT10) inhibitor. This compound inhibits tumors and weakens tumor resistance to antitumor drugs. Moreover, remodelin has been found to enhance healthspan in an animal model of the human accelerated ageing syndrome. In this study, we synthesized C-11-labelled remodelin ([11C]remodelin) for the first time as a positron emission tomography (PET) probe and assessed its biodistribution in mice using PET.Results[11C]Remodelin was synthesized by the reaction of a boron ester precursor (1) with hydrogen [11C]cyanide, which was prepared from the cyclotron-produced [11C]carbon dioxide via [11C]methane. The decay-corrected radiochemical yield of [11C]remodelin was 6.2 ± 2.3% (n = 20, based on [11C]carbon dioxide) with a synthesis time of 45 min and radiochemical purity of > 90%. A PET study with [11C]remodelin showed high uptake of radioactivity in the heart, liver, and small intestine of mice. The metabolite analysis indicated moderate metabolism of [11C]remodelin in the heart.ConclusionsIn the present study, we successfully synthesized [11C]remodelin and assessed its biodistribution of radioactivity in the mouse organs and tissues with PET. We are planning to prepare tumor and inflammatory models in which overexpression of NAT10 is possibly induced and conduct PET imaging for these animal models with [11C]remodelin to elucidate the relationship between NAT10 and diseases.

Lessons learned from syndemic HIV research in an immigrant, latinx sexual and gender minority community

The HIV incidence rate in Miami-Dade County is among the highest in the United States, with Latinx sexual and gender minority (SGM) groups experiencing a disproportionate burden. Despite extensive efforts by both private and public sectors to curb transmission and improve pre-exposure prophylaxis (PrEP) uptake, Latinx SGM groups continue to have high rates of HIV and low PrEP uptake compared to SGM groups overall. Using data collected from a biobehavioral study of the socio-structural factors affecting HIV susceptibility and PrEP uptake among Latinx SGM subgroups in Miami-Dade County, this paper shares lessons learned and provides concrete recommendations for tailoring survey research and biospecimen collection among a largely immigrant, socioeconomically disadvantaged community that is especially vulnerable to HIV. By drawing inferences from study data and contextualizing these with community partners, we learned: (1) Large parts of the target community may be unfamiliar with the underlying constructs captured in important HIV-related measures; (2) Cash incentives may shift motivation from intrinsic to extrinsic and lead to poorer data quality; (3) Deviations in Spanish go beyond vocabulary used in different Latin American countries, and more formal Spanish may relay concepts in unfamiliar ways that are unapproachable; and (4) community members may be unfamiliar with survey data collection processes and the protections in place to ensure confidentiality. These lessons and associated recommendations may help improve recruitment, study design, analysis, and community engagement in future studies, building trust and ultimately reducing the burden of HIV in these communities.

P-50. Mpox Vaccine Uptake Among Sexual and Gender Minority Veterans With and Without HIV in a Nationwide US Veteran Cohort

Abstract Background Sexual and gender minorities (SGM) and people with HIV have been disproportionately affected by the Mpox pandemic. Vaccination is recommended for those who may be at an increased risk. We examined the uptake of Mpox vaccine nationally in the Veterans Health Administration (VHA) among SGM Veterans and reported on disparities across groups. Methods We queried VHA’s national database to identify Veterans whose sexual orientation is recorded as lesbian, gay, bisexual or queer (LGBQ+) and gender identity as transgender woman (TGW)/man (TGM), non-binary or another gender (except cisgender) [transgender or gender diverse (TGD)] as of April 2024. Birth sex male LGBQ+ and TGD Veterans of both birth sexes were included in the cohort, stratified by age, race/ethnicity and HIV status. Within these cohorts we quantified receipt of JYNNEOS vaccine in the VHA starting 2022. Results Among the 42,434 males who identify as LGBQ+, 4759 (11.2%) had received at least one dose of the JYNNEOS vaccine; of these, 74% completed the series. There were large variabilities in vaccine uptake among LGBQ+ males by age: the 19-29 cohort had the lowest uptake at 5.2% and lowest series completion rate at 58.1% while the 50-59 age group had the highest uptake at 15.6% (Figure 1). Among racial groups, Asian LGBQ+ males had the highest uptake at 19.3%, and Whites had the lowest uptake at 9.4% (Figure 2). Black and Hispanic LGBQ+ males had better than average uptake at 14.7% and 15.6% respectively. Among 111,338 Veterans who identify as TGD, only 138 (1.2%) had received at least one dose by the end of observation period. Among these, TGW had the highest number of persons vaccinated (n=73) but non-binary Veterans had highest rate at 2.6% (Figure 3). Those with HIV were much more likely to have received at least one dose of the vaccine compared to those without (LGBQ+ males 25.5% vs. 7.6%; TGD 15.1% vs. 1%) (Figure 4). Conclusion TGD Veterans were much less likely to have received Mpox vaccination in the VHA compared to LGBQ+ males, with HIV status being the strongest predictor of vaccination in both groups. While the overall rates of Mpox vaccination appear lower in the VHA compared to general population, we did not see racial disparities that have been reported in Blacks but observed age related differences. Disclosures All Authors: No reported disclosures

P-2189. The Integration of Hepatitis C Treatment into Rural Syringe Services Programs via Telehealth: A Highly Effective Care Model

Abstract Background Direct acting antivirals (DAA) effectively cure Hepatitis C (HCV) infection; however, uptake among people who inject drugs (PWID) is low due to social determinants of health and healthcare system barriers. We present a telehealth model of HCV care integration into syringe services programs (SSPs).Figure 1. The HCV Care Continuum through ACCESS Telehealth, a program to integrate hepatitis C and opioid use disorder care into rural Maryland syringe services programs.Note: At time of analysis 6 were pending insurance approval, 15 patients were still on treatment, and 10 had not yet reached the time point for SVR 12 assessment. Methods The Johns Hopkins Viral Hepatitis Center implemented ACCESS Telehealth in collaboration with the Maryland Department of Health Center for Harm Reduction Services. Partnering with individual SSPs, context evaluation, HCV testing workflows, referral pathways for HCV/Opioid Use Disorder (OUD) care, SSP staff training, and SSP-based private space for telemedicine-equipped encounters were established. Services began in August 2021 in three rural Maryland SSPs and expanded to two more in 2022. SSP staff refer clients to low threshold, HCV/OUD treatment. An off-site nurse case manager provides patient education and support, collaborating with SSP-based Certified Peer Recovery Specialists. Specialists offer HCV/OUD treatment at the SSPs via telemedicine. Appointment, prescription, and laboratory information were extracted from the electronic medical record. DAA initiation and completion was confirmed by pharmacy records. Sustained virologic response (SVR) was defined as HCV RNA &amp;lt; 15 IU/ml measured &amp;gt;12 weeks after treatment completion. Results Of 282 patients scheduled for appointments, 84% (n=236) were white, 48% (134) were female, the median age of 39 years (interquartile range, 34-47) and 3% (11) were HIV-coinfected. Confirmatory labs were completed in 74% (210) of whom 23% (48) had spontaneously cleared HCV. Of 162 patients with detectable viremia, 92% (149) attended a provider visit, 90% (134) of those who attended a visit started treatment, 81% (108) of those who started treatment completed treatment, and 47% (51) of those who completed treatment had SVR labs drawn, of which 100% (51) achieved SVR (Figure 1). Overall, 45% (126) were prescribed buprenorphine. Conclusion We demonstrate an effective model for HCV care integration into rural SSPs with high uptake and completion of curative HCV treatment ( &amp;gt;80%). However, more than half did not complete post-treatment evaluation to confirm HCV response. Strategies for care after HCV treatment are needed. Disclosures Sherilyn Brinkley, MSN, CRNP, AbbVie: Honoraria|Gilead Sciences: Honoraria Mark S. Sulkowski, MD, AbbVie: Advisor/Consultant|Aligos Therapeutics: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Grant/Research Support|Precision Biosciences: Advisor/Consultant|Vir: Grant/Research Support|Virion: Advisor/Consultant Oluwaseun Falade-Nwulia, MBBS ,MPH, Abbvie Inc: Grant/Research Support|Gilead Sciences: Advisor/Consultant

P-2207. HCV Reinfection is Associated with Cocaine Use and Ongoing Injection Drug Use in People with OUD: Outcomes from the ANCHOR and LOOP Studies

Abstract Background Despite achieving sustained virologic response (SVR), people with HCV, opioid use disorder (OUD) and ongoing injection drug use (IDU) remain at risk of reinfection. Identification and retreatment of reinfected individuals is critical to HCV elimination. We sought to evaluate the rate of HCV reinfection, factors associated with reinfection, and retreatment in a cohort of people who inject drugs (PWID).Table 1.Bivariate analysis of baseline sociodemographic characteristics. Methods The ANCHOR study provided HCV treatment for 198 people with chronic HCV, OUD, and recent opioid use. Those who achieved SVR underwent screening for HCV reinfection, with retreatment initiated per standard of care. At each visit, surveys were administered to evaluate ongoing risk behaviors and medication for OUD (MOUD) status. Patients were followed for 96 weeks with optional enrollment in a 2-year extension study (LOOP).Table 2.Bivariate (IRR) and multivariable (aIRR) analyses of factors associated with HCV reinfection. Results 158 individuals achieved SVR and were followed after treatment completion for 353 person-years, median 90 weeks (IQR 84-160 weeks). Subjects were predominantly male (69%), Black (84.2%), middle-aged (58 years), and HIV-negative (94.9%). Twenty individuals (12.7%) were reinfected a median of 77 weeks (IQR 60-105 weeks) after HCV treatment, at a rate of 5.7/100 person-years. Reinfection was associated with cocaine use (p&amp;lt; 0.001) and IDU in the past month (p=0.005). Of the 20 reinfected individuals, 16 (80%) initiated HCV re-treatment a median of 26 weeks after detection (IQR 4-64 weeks), with 12 (75%) achieving SVR, 1 currently on treatment, and 5 deaths.Figure 1.Kaplan-Meier reinfection free survival curve assessing associations of cocaine use with HCV reinfection. Conclusion In this cohort of people with OUD recently cured of HCV, we observed moderate rates of HCV reinfection associated with cocaine use and past month IDU, with high rates of retreatment uptake and SVR. These data highlight that in people with active drug use, longitudinal follow-up for retesting and retreatment is critical for HCV elimination. Enhanced accessibility to and engagement with harm-reduction services – such as syringe service programs - and interventions specifically addressing polysubstance use are crucial to reducing ongoing HCV transmission and reinfection. Disclosures Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support

P-631. RSV Prophylaxis with Nirsevimab in Infants: Systematic Review of Early Real-World Evidence on Effectiveness and Impact

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections and hospitalizations among infants worldwide. In 2023, the universal RSV immunization of all infants with the novel monoclonal antibody nirsevimab was introduced in several countries. This systematic review aims to summarize early real-world evidence on achieved immunization rates as well as on the impact and effectiveness of nirsevimab prophylaxis among infants. Methods A systematic literature search for full-text publications was conducted in the databases PubMed and Embase. The review included observational studies that investigated the impact or effectiveness of nirsevimab in routine use. Clinical research, decision analytic modeling studies, and studies describing the disease burden of RSV without direct reference to nirsevimab use were excluded. Results Five studies fulfilled the inclusion criteria, including one from the United States (US), one from Luxembourg, and three studies from different regions in Spain. Population-wide immunization rates were reported in Luxembourg and several Spanish regions, all exceeding 80%. Four studies estimated the effectiveness of nirsevimab in preventing RSV-related hospitalizations, including two population-based cohort studies and two case-control studies. The effectiveness of nirsevimab in preventing RSV-related hospitalizations was calculated at 88.7% (95%-CI: 70-96), 84.4% (95%-CI: 77-90), and 82.0% (95%-CI: 66-90) in the Spanish studies and 90% (95 %-CI 75-96) in the US. While no effectiveness estimate was reported in Luxembourg, the number of RSV-related hospitalizations among infants under 6 months decreased by 69% after nirsevimab introduction compared to the same period of the previous year. Conclusion High uptake was observed in both Luxembourg and Spain. Despite methodological differences between studies and varying implementation strategies between countries, observed effects of recommending nirsevimab to all infants were largely consistent. International evidence suggests that nirsevimab substantially reduces RSV-related hospitalizations and thus relieves the burden on healthcare systems during the RSV season. Disclosures Moritz Wick, MSc, Sanofi: Employee|Sanofi: Stocks/Bonds (Public Company) Anna C. Meyer, PhD, Sanofi: Employee Oliver Damm, PhD, Sanofi: Employee Annika Wülfing, PhD, Sanofi: Employee and may hold stocks Oliver Martyn, MPH, Sanofi: Employee of Sanofi|Sanofi: Stocks/Bonds (Public Company) Rolf Kramer, PhD, Sanofi: Employee of Sanofi|Sanofi: Stocks/Bonds (Public Company)

Exploring Parent-Driven Determinants of COVID-19 Vaccination in Indigenous Children: Insights from a National Survey

Background: Globally and in Canada, Indigenous populations have faced heightened vulnerability during pandemics, with historical inequities exacerbated by multigenerational colonial policies. This study aimed to identify parental factors influencing COVID-19 vaccination among Indigenous children in Canada. Methods: Data from a nationally representative, cross-sectional survey of parents/guardians with children under 18 years of age were analyzed. The study focused on Indigenous children, examining vaccine uptake, parental hesitancy, and related sociodemographic factors. Multivariable logistic regression models were employed to identify key predictors of COVID-19 vaccination. Results: COVID-19 vaccine coverage among Indigenous children was 61.8%, with higher uptake among Inuit (74.4%) children compared to Métis (61.2%) and First Nations (59.6%) children. Nearly half of Indigenous parents (53.4%) expressed hesitancy, primarily due to perceived concerns about insufficient research on the vaccine in children. Higher vaccine uptake was associated with parental education, adherence to routine vaccinations, and urban residence. Conversely, parental hesitancy, particularly related to medical concerns, significantly decreased the likelihood of vaccine uptake. Conclusions: The study highlights the complexity of vaccine hesitancy among Indigenous parents. Targeted interventions, including culturally adapted educational initiatives, community engagement, and healthcare provider advocacy, are essential to improve vaccine uptake.

Abstract B005: Copper-67 based targeted radioligand therapy to the somatostatin receptor 2 (SSTR2) provides added efficacy and may prime small cell lung cancer for immunotherapy

Abstract Background and Purpose: Immune checkpoint therapy (ICT) has revolutionized cancer treatment; however, efficacy remains poor for some cancers, including small cell lung cancer (SCLC). Strategies to enhance immune responses include combining ICT with other existing cancer therapies. Targeted radioligand therapy uses a radiolabeled cancer-targeting vector, allowing for specific delivery of radiation to all tumor sites while minimizing radiation exposure to healthy tissues. Targeted Copper Theranostics (TCTs) is a targeted radioligand platform utilizing copper-64/67. We evaluated [67Cu]Cu-SARTATE in combination with ICT in a murine animal model using RP116 tumor cells. Methods: We administrated ∼5 MBq [64Cu]Cu-SARTATE to RP116 (a murine SCLC cell line expressing SSTR2) tumor- bearing immunocompetent C57BL/6 mice and assessed biodistribution and tumor uptake via PET imaging at 1, 4 and 24 h post IV injection. After completion of a dose escalation study, an efficacy study using [67Cu]Cu-SARTATE, mouse ICT analogues and the combination of [67Cu]Cu-SARTATE and ICT treatment groups in the same animal model was performed to evaluate therapeutic efficacy of copper-67-based TCT. Results: Tumor uptake of [64Cu]Cu-SARTATE was visualized by PET imaging over the first 24 h post-injection with high tumor uptake, consistent with multiple studies previously published showing uptake in human xenograft models with the same product. Tumor uptake of [67Cu]Cu-SARTATE was confirmed by ex vivo biodistribution and Cherenkov imaging, with no significant radiotoxicity observed via body condition and body weight measurements in mice receiving injected activities up to the maximum tested dose of 30 MBq. The combination of 30 MBq [67Cu]Cu-SARTATE, with both anti-PD-L1 and anti-CTLA4, improved median survival by 3, 7, or 13 days, compared to ICT-only (anti-PD-L1 plus anti-CTLA4), [67Cu]Cu-SARTATE-only or saline-only treated groups respectively. Conclusion: Biodistribution studies demonstrated high tumor-specific uptake for [64Cu]- and [67Cu]-Cu-SARTATE in this mouse syngeneic SCLC model. A dose escalation study demonstrated copper-67-based TCT could be used to effectively inhibit tumor growth with minimal radiotoxicity. The combination of TCT with ICTs improved overall survival compared to single-treatment control groups. Collectively, our results demonstrate that [67Cu]Cu-SARTATE in combination with ICTs improves overall survival. [67Cu]Cu-SARTATE may prime immunologically “cold” SCLC tumors to improve responsiveness to ICTs through a synergistic response. Tumor biomarkers are being investigated to understand how immune infiltration differs depending on treatment regime. Citation Format: Jaclyn L. Lange, Kurt R. Gehlsen, Lachlan E. McInnes, Jessica Van Zuylekom, Benjamin Blyth, Stacey E. Rudd, Paul S. Donnelly, Matt Harris. Copper-67 based targeted radioligand therapy to the somatostatin receptor 2 (SSTR2) provides added efficacy and may prime small cell lung cancer for immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B005.

Abstract B026: Development of a novel theranostic agent targeting MET in lung and head and neck cancer

Abstract Background: The mesenchymal transcript factors is a receptor tyrosine kinase that when dysregulated or overexpressed can stimulate oncogenesis. Alterations in MET are found in 5% of non-small cell lung cancer but are also found in head and neck cancer and in cancers resistant to tyrosine kinase inhibitors targeting other oncogenic drivers. Our objective is to evaluate a novel, camelid-derived, MET binding antibody as a potential theranostic agent used in MET expressing cancers. Methods: The anti-MET VHH camelid antibody, 1E7-Fc, was identified from a phage display library. Binding to human MET was assessed via serially diluted ELISA analysis and bio-Layer interferometry. Western blot and qRT-PCR analysis was used to assess MET and p-MET expression in established multiple lung cancer (EBC-1 and UW-Lung-21) and head and neck cancer (Detroit 562, UM-SCC47, and UPCI:SCC90) cell lines where inhibition was compared to treatment with the MET inhibitor, capmatinib. Binding affinity and internalization of 1E7-Fc to these cell lines was assessed via flow cytometry and immunofluorescence. EC50 assays were performed to measure the effects of 1E7-Fc on cell viability. Bioconjugation of 89Zr and 177Lu enabled tumor uptake imaging in xenograft models using PET/CT and SPECT imaging, respectively. The efficacy of [89Zr]Zr-1E7-Fc as an imaging agent targeting MET expression in vivo was investigated through PET/CT imaging, region of interest (ROI) image analysis, and ex vivo activity. Results: 1E7-Fc demonstrates a high binding affinity for human MET. Binding to MET expressing cell lines correlated to levels of MET expression and was seen even in cells resistant to MET inhibitor capmatinib. 1E7-Fc did not cause disrupt MET signaling and did not impair cell proliferation. [89Zr]Zr-1E7-Fc demonstrated rapid localization and high tumor uptake in EBC-1, UW-Lung-21, and Detroit 562 xenografts with rapid clearance from circulatory systems as tumor to blood ratios were 2.7, 2.5, and 1.8 forty-eight hours post injection, respectively.1E7-Fc was successfully labeled with 177Lu and imaged by SPECT. Conclusions: Our preclinical findings indicate that the camelid antibody MET-1E7-Fc has potential as an imaging agent for high MET-expressing cancers. Further studies are needed to assess the therapeutic response to 177Lu-conjugated antibodies and to translate these results to patients. Citation Format: Rachel L. Minne, Natalie Y. Luo, Caroline M. Mork, Madalynn R. Wopat, Jayden L. West, Jessica E. Griffin, Karla Esbona, Saahil Javeri, Kwangok P. Nickel, Reinier Hernandez, Aaron M. LeBeau, Randall J. Kimple, Andrew M. Baschnagel. Development of a novel theranostic agent targeting MET in lung and head and neck cancer. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B026.

Efficient CO2 Capture Using Nitrogen-Enriched Microporous Carbon Derived from Polybenzoxazine in a Single-Step Process for Environmental Sustainability

In this research, we successfully synthesized nitrogen-enriched microporous carbon through a meticulous process involving two different activation procedures. Initially, polybenzoxazine was carbonized at 800 °C to create a precursor material, which was then activated with two different activating agents (KOH and KMnO4) at the same temperature. This activation significantly enhanced the material’s porosity, increasing its specific surface area from 335 m2/g (KOH activated) to 943 m2/g (KMnO4 activated). XPS analysis confirmed the presence of nitrogen functionalities, including secondary-N, oxide-N, pyridone-N, and pyridine-N, which are critical for CO2 adsorption. Adsorption tests demonstrated a high CO2 uptake of 3.8 mmol/g at 25 °C and 1 bar, driven by a combination of physisorption (physical interaction with the surface area) and chemisorption (chemical interaction with nitrogen sites). This high adsorption capacity can be attributed to the carbon’s substantial surface area, significant micropore volume, and the interconnected network of pores, which together provide structural stability and facilitate the diffusion of CO2 molecules. These findings suggest that this nitrogen-enriched microporous carbon, derived from polybenzoxazine, holds significant promise as a highly efficient material for applications in CO2 capture and storage.

Detectability of Al18F-NOTA-HER2-BCH PET for Nodal Metastases in Patients With HER2-Positive Breast Cancer.

The aim of this study was to compare Al18F-NOTA-HER2-BCH and 18F-FDG for detecting nodal metastases in patients with HER2-positive breast cancer on PET/CT. In this retrospective study, 62 participants with HER2-positive breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. Participants were pathologically confirmed as HER2-positive (IHC 3+ or IHC 2+ with gene amplification on FISH). Three independent readers visually assessed uptake of tracers on imaging. Furthermore, the diagnostic accuracy of nodal metastases was assessed using c-statistics. The lesion uptakes were quantified by SUVmax and target-to-background ratio (TBR) and compared using the general linear mixed model. The findings showed nodal metastases in 33 (53%) participants, including 45% only with regional nodal metastasis and 55% with nonregional nodal metastasis. On per-patient level, the sensitivity and specificity of Al18F-NOTA-HER2-BCH and 18F-FDG based on the majority reads were 0.97, 0.97, and 0.85, 0.77, respectively. Five participants were visualized only on Al18F-NOTA-HER2-BCH. Seven participants with high uptake only on 18F-FDG PET/CT were confirmed to be inflammatory uptake by pathological results and later imaging follow-up. On per-lesion level, Al18F-NOTA-HER2-BCH PET/CT detected more axillary (98.8% vs 70.2%), extra-axillary (100% vs 61.7%), and nonregional (99.1% vs 67.0%) lymph nodal metastases than 18F-FDG PET/CT. Additionally, Al18F-NOTA-HER2-BCH PET/CT detected more nodal metastases small than 10 mm than 18F-FDG PET/CT (198 vs 125, 99.5% vs 62.8%). The median SUVmax and TBR of regional or nonregional nodal metastases at Al18F-NOTA-HER2-BCH were all higher than those on 18F-FDG (range of median SUVmax, 8.0-11.4 vs 2.3-5.6; P range, <0.001-0.007; range of median TBR, 7.3-16.3 vs 2.9-5.3; P range, <0.001). No adverse reactions related to imaging agents were observed in all participants. Al18F-NOTA-HER2-BCH PET/CT detected more regional and nonregional lymph nodal metastases in patients with HER2-positive breast cancer than on 18F-FDG PET/CT, especially for lesions small than 10 mm.

68Ga-FAPI-04 Outperforms 18F-FDG in Detecting Lesions for Primary Leiomyosarcoma of Bone: A Rare Case.

Primary leiomyosarcoma of bone (PLB) is an ultrarare tumor, characterized by its aggressive clinical behavior, high heterogeneity, and dismal prognosis. Here, we present the 68Ga-FAPI-04 and 18F-FDG PET/CT findings in a case of PLB affecting the left femur. FAPI PET/CT showed more bone lesions and higher uptake in the multiple metastatic lesions compared with FDG PET/CT. More interestingly, FAPI PET/CT could clearly detect the tumor embolus on the left common femoral artery, which was negative on FDG. This case suggests that FAPI PET/CT is a promising method for the primary diagnosis and staging of PLB.