High Uptake Research Articles

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.

Integrated biorefinery approach for sustainable production of biodiesel, bioplastics and high value bioproducts from a bloom forming alga, Botryococcus braunii.

The global shift towards sustainable energy and bioproducts has intensified research on algae. Renewable green biofuel can address and provide solutions to both energy crisis and climate change challenges. Botryococcus braunii, a bloom forming green microalga, known for its high lipid content and potential for biofuel production has been explored in the present study. The study envisages the utilisation of algal blooms in freshwater ecosystems for the production of biodiesel and high value bioproducts through an integrated biorefinery approach. During the peak bloom, the algal cell densities reached up to 3.3×106 colonies L-1 with significant shift in water quality due to high nutrient uptake. Gas chromatography-mass spectroscopic analysis revealed high concentration of saturated and monounsaturated fatty acids, particularly hexadecanoic acid (C16:0) and 9-octadecenoic acid (C18:1) which are essential for stable, energy-rich biodiesel production. Hydrocarbons including squalene, botryococcenes, and botryococcane, produced by this alga have significant industrial applications. The high polyhydroxybutyrate (PHB) content in the alga emphasises its potential for sustainable bioplastic production. Growth conditions, lipid content, and biochemical composition of B. braunii were investigated. Algal blooms can provide a sustainable and economically viable source of biofuel with high value co-products. This approach not only contributes to renewable energy solutions through valorising a waste bioresource but in combination with other mass cultivation strategies can also offer a means to sustainably manage the impact of algal blooms on aquatic ecosystems.

Preclinical Evaluation of 68Ga/177Lu-Labeled FAP-Targeted Peptide for Tumor Radiopharmaceutical Imaging and Therapy.

Fibroblast activation protein (FAP) has been considered a promising target for tumor imaging and therapy. This study designed a novel peptide, FAP-HXN, specifically targeting FAP and exhibiting significant potential as a radionuclide-labeled theranostic agent. Preclinical studies were conducted to evaluate the potency, selectivity, and efficacy of FAP-HXN. Methods: FAP-HXN was synthesized and characterized for selectivity and specificity toward FAP. Cellular uptake of the radiolabeled FAP-HXN in human embryonic kidney (HEK)-293-FAP cells with high expressions of FAP was evaluated. The diagnostic and therapeutic potential of 68Ga- and 177Lu-labeled radioligands was evaluated in HEK-293-FAP tumor-bearing mice compared with the FAP-targeting peptide FAP-2286. Results: FAP-HXN demonstrated high binding ability to human and mouse sources of FAP. Moreover, the invivo studies confirmed the high affinity and specificity of radiolabeled FAP-HXN. Small-animal PET imaging demonstrated that [68Ga]Ga-FAP-HXN had continuous tumor uptake in FAP-positive tumors after administration compared with [68Ga]Ga-FAP-2286. In the therapeutic experiments, [177Lu]Lu-FAP-HXN showed significant antitumor activity in HEK-293-FAP xenografts at well-tolerated doses, which also exhibited longer tumor retention and better tumor growth inhibition compared with [177Lu]Lu-FAP-2286. Conclusion: The preclinical studies revealed that radiolabeled FAP-HXN had high tumor uptake, prolonged retention, and significant anticancer efficacy in HEK-293-FAP xenografts. FAP-HXN shows promising potential as a novel theranostic radioligand for FAP-positive tumors.

18F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function.

The ovary is an important female organ not only for pregnancy but also for the regulation of life activities via hormone release. Ovarian function is measured by blood hormone levels, but the hormone level reflects only the ovarian reserve and no other essential ovarian functions, such as nurturing and expelling follicles. Ovarian fibrosis is related to essential ovarian function; however, the existing methods for evaluating fibrosis are invasive. Ovarian fibrosis has been reported to be associated with mitochondrial function. We hypothesized that positron emission tomography (PET) imaging of mitochondria could be a new, non-invasive method for evaluating essential ovarian function. In this study, we investigated the age-related changes in ovarian fibrosis using the mitochondrial complex-I (MC-I) PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF). Aged rats, whose ovary function decline, exhibited a higher uptake of [18F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [18F]BCPP-EF uptake in the ovary was associated with ovarian fibrosis, but not with AMH level which reflects the ovarian reserve. Furthermore, the measurement of MC protein levels showed that the protein levels of MC-I increased with age, whereas those of MC-V decreased. This study demonstrated that [18F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [18F]BCPP-EF-PET is a useful non-invasive method for evaluating essential ovarian functions and will contribute to basic research on ovarian aging as well as drug discovery targeting ovarian dysfunction.

Imidazolium-Functionalized Ionic Porous Organic Polymer for Efficient Removal of Oxo-Anions Pollutants from Water

The development of highly efficacious materials for the removal of toxic heavy metal-based oxo-anions is of utmost importance. Herein, an ionic porous organic polymer (designated as HB-IPOP) was synthesized through a quaternization reaction between hexa(imidazole-1-yl)benzene and 5,5′-Bis(bromomethyl)-2,2′-bipyridine. HB-IPOP exhibited high saturation uptake capacities, specifically 292 mg·g−1 for Cr2O72− and 531 mg·g−1 for ReO4−, and demonstrated exceptional selectivity for both Cr2O72− and ReO4−. Additionally, HB-IPOP demonstrates high recyclability, allowing its reuse over at least five cycles. DFT calculations confirmed that the superior interaction sites and binding energies of HB-IPOP with Cr2O72− and ReO4− outperform the affinities of other competing anions. This theoretical validation aligns with the experimentally observed high capacity and selectivity of HB-IPOP for these oxo-anions. Hence, HB-IPOP emerges as a promising candidate to replace current adsorbent materials in the effective removal of Cr2O72− and TcO4− anions from water.

Lutetium-177 labeled iPD-L1 as a novel immunomodulator for cancer-targeted radiotherapy

BackgroundCancer immunotherapy is a relatively new approach to cancer treatment. Peptides that target specific pathways and cells involved in immunomodulation can potentially improve the efficacy of cancer therapy. Recently, we reported iPD-L1 as a novel inhibitor peptide that specifically targets the cancer cell ligand PD-L1 (programmed death ligand 1). PD-L1 is responsible for inhibiting the immune checkpoint protein PD-1 expressed by regulatory T cells. On the other hand, anti-PD-L1 immunotherapy in combination with external beam radiotherapy has shown improved outcomes in the treatment of breast and lung cancer. The aim of this research was to prepare 177Lu-labeled iPD-L1 and to preclinically evaluate its radiotherapeutic potential and role as a tumor immunomodulator by measuring macrophage activation, IL-10, TGFβ, and PD-L1 expression in 4T1 triple-negative breast cancer cells and murine 4T1 tumors after treatment with 177Lu-iPD-L1.ResultsThe iPD-L1 ligand, characterized by UPLC mass, UV-Vis, and FT-IR spectroscopies, showed a chemical purity of 99%. The 177Lu-iPD-L1 radiochemical purity was 98.9 ± 1.1%. In vitro and in vivo studies demonstrated radiotracer stability in human serum (> 97% after 24 h evaluated by radio-HPLC), adequate affinity by the PDL1 protein (IC50 = 4.21 nM), and specific detection for PD-L1 assessed in 4T1, HCT116, and AR42J cancer cells, in which PD-L1 expression was verified by immunofluorescence and Western Blot assays. After treatment with 177Lu-iPD-L1 (0.4 Bq/cell), flow cytometry results showed a significant decrease in cell viability of 4T1 cells (dead 56.2%) compared to 177LuCl3 (dead 34.2%) and untreated cells (dead 9.4%). With high tumor uptake (6.97 ± 1.04%ID) and hepatobiliary and renal clearance, lutetium-177-labeled iPD-L1 delivered a tumor dose of 27 Gy/37 MBq and less than 0.36 Gy/37 MBq to non-source organs. PD-L1 positive tumors showed a significant increase in activated macrophages, PD-L1, IL-10, and TGFβ expression levels after 177Lu-iPD-L1 treatment as evaluated by ELISA assay and immunohistochemistry.ConclusionsTherefore, this study warrants further dosimetric and clinical studies to determine the immunomodulatory effect and therapeutic efficacy of 177Lu-iPD-L1 in treating PD-L1-positive tumors in combination with anti-PD-1/PD-L1 immunotherapy protocols.

Nationwide representative serosurvey of third-grade school children to evaluate the hepatitis B vaccination impact in Kyrgyzstan, 2022

BackgroundKyrgyzstan introduced universal hepatitis B childhood vaccination in 1999 to reduce the burden of hepatitis B. In 2016, aligned with the goal of controlling hepatitis B in the WHO European Region, a regional target of 0.5% was set for seroprevalence of hepatitis B surface antigen (HBsAg) among targeted birth cohorts. We conducted a representative nationwide serosurvey to assess the HBsAg prevalence among third-grade school children in Kyrgyzstan in 2022.MethodsWe sampled numbers of children proportional to the population size and stratified the sample by region and urbanization level (urban/rural). We applied multistage cluster sampling with school classes as clusters. Identified participants in the survey were tested for HBsAg, using Enzyme-linked Immunosorbent Assay (ELISA), and positive samples confirmed with neutralization tests. Data on vaccination coverage for hepatitis B birth dose (HepB BD), including timing, and three doses of hepatitis B vaccine (HepB3) were collected from medical vaccination records. We calculated crude and weighted proportions for HBsAg seroprevalence and HepB BD and HepB3 coverage.ResultsFrom the target sample size of 3,352 children, a total of 3,183 children (95%) participated in the survey. The majority of children were 9 or 10 years old (2,964; 93%) with almost equal numbers of girls and boys (1,606; 50% boys) and rural and urban participants (1,624; 51% urban). Five participants tested positive for HBsAg in confirmatory tests. The weighted HBsAg seroprevalence was 0.12% (95% CI 0.04–0.35%). Weighted coverage for HepB BD was 88% (95% CI 86–90%) and for HepB3 90% (95% CI 86–93%). Results from crude and weighted analysis did not differ statistically.ConclusionsOur study demonstrates the impact of a successfully implemented hepatitis B vaccination programme in Kyrgyzstan. High hepatitis B vaccination coverage has resulted in very low HBsAg seroprevalence among vaccinated birth cohorts, paving the way towards the achievement of regional hepatitis B control targets. Maintaining high vaccination uptake plus additional measures like screening of pregnant women and treatment of those infected will be key to achieve elimination of vertical transmission of hepatitis B in Kyrgyzstan.

Polylactic acid microplastics before and after aging induced neurotoxicity in zebrafish by disrupting the microbiota-gut-brain axis.

Polylactic acid (PLA) is a biodegradable alternative to traditional plastics due to its excellent biocompatibility. However, PLA is challenging to fully degrade and can easily become microplastics (MPs) in surface water, a process accompanied by aging. This study found that aged PLA (APLA) MPs exhibited increased surface roughness, decreased surface potential, and more oxygen-containing functional groups compared to PLA. Acute exposure to PLA/APLA in zebrafish larvae resulted in sluggish behavior and inhibited neuronal development. Chronic exposure to PLA/APLA in adult zebrafish led to reduced exploratory behavior, poor memory, increased aggression, and neuron loss. Overall, PLA/APLA induced dose-dependent neurotoxicity, with APLA exhibiting greater toxicity than PLA, potentially due to its higher rate of uptake. Additionally, exposure to PLA/APLA led to thinning of the intestinal wall, shortening of villi, and suppression of intestinal neurotransmitter levels, accompanied by alterations in microbial abundance and gut dysbiosis. Meanwhile, supplementation with bile acid, considered as the key regulator in the gut-brain axis, significantly mitigated the neurotoxicity induced by PLA/APLA. These findings confirm that PLA/APLA MPs indeed elicit neurotoxicity via the gut-brain axis and provide scientific evidence for targeted environmental interventions to minimize the adverse ecological impacts of biodegradable MPs.

Porous Organic Polymers Incorporating Shape‐Persistent Cyclobenzoin Macrocycles for Organic Solvent Separation

AbstractThe recovery and separation of organic solvents is highly important for the chemical industry and environmental protection. In this context, porous organic polymers (POPs) have significant potential owing to the possibility of integrating shape‐persistent macrocyclic units with high guest selectivity. Here, we report the synthesis of a macrocyclic porous organic polymer (np‐POP) and the corresponding model compound by reacting the cyclotetrabenzil naphthalene octaketone macrocycle with 1,2,4,5‐tetraaminobenzene and 1,2‐diaminobenzene, respectively, under solvothermal conditions. Co‐crystallization of the macrocycle and the model compound with various solvent molecules revealed their size‐selective inclusion within the macrocycle. Building on this finding, the np‐POP with a hierarchical pore structure and a surface area of 579 m2 g−1 showed solvent uptake strongly correlated with their kinetic diameters. Solvents with kinetic diameters below 0.6 nm – such as acetonitrile and dichloromethane – showed high uptake capacities exceeding 7 mmol g−1. Xylene separation tests revealed a high overall uptake (~34 wt %), with o‐xylene displaying a significantly lower uptake (~10 wt % less than other isomers), demonstrating the possibility of size and shape selective separation of organic solvents.

Intratumoral Heterogeneity of Primary Breast Cancer on 18F-FES PET/CT and dbPET Anticipated a Heterogeneous Response to Chemotherapy.

A 59-year-old woman with cT3N3M1 invasive breast cancer (ER low positive, PgR positive, HER2 negative) underwent PET/CT and dedicated breast PET scans using 18F-FDG and 18F-fluoroestradiol (18F-FES). While most primary tumor regions displayed low FES uptake, regions of high FES uptake were also identified. Following chemotherapy with the paclitaxel and bevacizumab, 18F-FDG PET/CT demonstrated a favorable response, but residual disease was noted in areas with high FES uptake on the pretreatment images. This case illustrated that 18F-FES PET can depict intratumoral heterogeneity within the primary tumor, which was strongly associated with a heterogeneous response to subsequent chemotherapy.

Synthesis of pillar-layered metal-organic frameworks with variable backbones through sequence control.

The properties and functions of metal-organic frameworks (MOFs) can be tailored by tuning their structure, including their shape, porosity and topology. However, the design and synthesis of complex structures in a predictable manner remains challenging. Here we report the preparation of a series of isomeric pillar-layered MOFs, and we show that their three-dimensional topology can be controlled by altering the layer stacking. This enables variability on the backbone structure, as well as diverse spatial arrangements of pillars and the partitioning of pore space into several kinds of cages packing in distinct sequences. These sequence-controlled MOFs (SC-MOF-1-6) showcase ultrahigh benzene capture capacities at low-pressure and high volumetric and gravimetric uptake performances in high-pressure methane storage. We provide the construction principles of the SC-MOFs and predict nearly 2,000 possible SC-networks with sophisticated composition sequences at the atomic level by using a Python script.

Isoreticular Tolerance and Phase Selection in the Synthesis of Multi-Module Metal-Organic Frameworks for Gas Separation and Electrocatalytic OER.

Although metal-organic frameworks are coordination-driven assemblies, the structural prediction and design using metal-ligand interactions can be unreliable due to other competing interactions. Leveraging non-coordination interactions to develop porous assemblies could enable new materials and applications. Here, we use a multi-module MOF system to explore important and pervasive impact of ligand-ligand interactions on metal-ligand as well as ligand-ligand co-assembly process. It is found that ligand-ligand interactions play critical roles on the scope or breakdown of isoreticular chemistry. With cooperative di- and tri-topic ligands, a family of Ni-MOFs has been synthesized in various structure types including partitioned MIL-88-acs (pacs), interrupted pacs (i-pacs), and UMCM-1-muo. A new type of isoreticular chemistry on the muo platform is established between two drastically different chemical systems. The gas sorption and electrocatalytic studies were performed that reveal excellent performance such as high C2H2/CO2 selectivity of 21.8 and high C2H2 uptake capacity of 114.5 cm3/g at 298 K and 1 bar.

Isoreticular Tolerance and Phase Selection in the Synthesis of Multi‐Module Metal‐Organic Frameworks for Gas Separation and Electrocatalytic OER

Although metal‐organic frameworks are coordination‐driven assemblies, the structural prediction and design using metal‐ligand interactions can be unreliable due to other competing interactions. Leveraging non‐coordination interactions to develop porous assemblies could enable new materials and applications. Here, we use a multi‐module MOF system to explore important and pervasive impact of ligand‐ligand interactions on metal‐ligand as well as ligand‐ligand co‐assembly process. It is found that ligand‐ligand interactions play critical roles on the scope or breakdown of isoreticular chemistry. With cooperative di‐ and tri‐topic ligands, a family of Ni‐MOFs has been synthesized in various structure types including partitioned MIL‐88‐acs (pacs), interrupted pacs (i‐pacs), and UMCM‐1‐muo. A new type of isoreticular chemistry on the muo platform is established between two drastically different chemical systems. The gas sorption and electrocatalytic studies were performed that reveal excellent performance such as high C2H2/CO2 selectivity of 21.8 and high C2H2 uptake capacity of 114.5 cm3/g at 298 K and 1 bar.

A novel supramolecular nanodrugs for improving the cognitive function of schizophrenia by protecting active lactone of arecoline.

Over 30 % of patients with schizophrenia experience treatment resistance and severe side effects. The limited efficacy of antipsychotic therapies poses a challenge, partly due to the blood-brain barrier (BBB) and the non-selective targeting of these drugs. Herein, we report on arecoline (ARE), a water soluble natural small molecule, which was successfully constructed a phospholipid complex by noncovalent interactions. Most striking, this arecoline-phospholipid complex nanoplatforms (ARE-PC NPs) could prevent the hydrolyzation of its ester group by carboxylesterases, which showed sustained release, superior physiological stability and long circulatory capability. Both in vitro cells and in vivo mice speculated that this ARE-PC NPs might has a high cellular uptake and stronger penetration ability of the BBB. Additionally, our results demonstrated that this phospholipid complex might facilitate ARE delivery to the brain tissue and obviously improve the schizophrenia-like behavior in cuprizone induced animal models. This study highlights ARE-PC NPs as a promising antipsychotic nanodrug for the therapy of schizophrenia.

Evaluation of maSSS/maSES-PEG2-RM26 for their potential therapeutic use after labeling with Re-188. Could their [99mTc]Tc-labeled counterparts be used to estimate dosimetry?

BackgroundGastrin releasing peptide receptor (GRPR)-directed radiopharmaceuticals for targeted radionuclide therapy may be a very promising addition in prostate and breast cancer patient management. Aiming to provide a GRPR-targeting theranostic pair, we have utilized the Tc-99m/Re-188 radiometal pair, in combination with two bombesin based antagonists, maSSS-PEG2-RM26 and maSES-PEG2-RM26. The two main aims of the current study were (i) to elucidate the influence of the radiometal-exchange on the biodistribution profile of the two peptides and (ii) to evaluate the feasibility of using the [99mTc]Tc labeled counterparts for the dosimetry estimation for the [188Re]Re-labeled conjugates.ResultsBoth peptides were successfully labeled with Re-188 and evaluated both in vitro and in vivo. In GRPR expressing PC-3 cells, both [188Re]Re-labeled peptides displayed high cellular uptake (8.5 ± 0.1% and 5 ± 0.3% of added activity, respectively), heavily GRPR-driven, while retaining the radioantagonistic profile with slow internalization rates. Both agents demonstrated high receptor affinity when loaded with natRe (7.5 nM and 8 nM, respectively). When tested in vivo in GRPR expressing PC-3 xenografts, both radioantagonists demonstrated high tumor accumulation (6.3 ± 0.5%IA/g and 5 ± 1%IA/g at 1 h pi, respectively), with good retention over time (4 ± 2%IA/g and 3.1 ± 0.1%IA/g at 4 h pi, respectively). In addition, their biodistribution profiles were closely mimicking their [99mTc]Tc-labeled counterparts. Statistically significant lower tumor uptake was found for both conjugates labeled with Tc-99m, which may result in underestimation of the dose delivered to the tumor.ConclusionsAll the results indicate that Tc-99 m could be used for dosimetry evaluation for the two [188Re]Re-labeled radioligands, with minimal alterations in their biodistribution pattern and tumor targeting capabilities.

Comparison of cadmium pathways in a high Cd accumulating cultivar versus a low Cd accumulating cultivar of Theobroma cacao L.

Understanding cadmium (Cd) pathways in cacao trees is critical for developing Cd mitigation strategies. This study investigates whether Cd uptake and translocation mechanisms differ between a low and a high Cd-accumulating cacao cultivar. We sampled three replicate trees of each cultivar, and a grafted cultivar that shared the same scion as the low Cd accumulator but had a different rootstock. All cultivars grew in the same field with similar bioavailable soil Cd. We utilized Cd stable isotope analyses to trace Cd pathways within the trees, complemented by micro-scale imaging of Cd distribution in leaves and branches, and nutrient and Cd quantification across tree organs. The high Cd accumulator exhibited 2.9-fold higher Cd uptake than the low Cd accumulator, while the grafted cultivar showed 1.7-fold higher uptake. These differences matched Mn uptake. The δ114/110Cd values of organs increased in the order: roots≤nibs, young leaves≤branches≤pod husks<mature leaves for the high and grafted cultivar, and nibs≤roots≤branches≤pod husks<mature leaves for the low cultivar. The enrichment in heavy isotopes correlated with a progressive retention of Cd compared to Mn along the xylem pathway from roots to branches to leaves. The differences in Cd isotope compositions between cultivars indicate that there are differences in translocation processes, yet they did not affect the relative Cd internal distribution. Cd mass balances and internal translocation factors (ITF) corroborated that differences in nib Cd concentrations among cultivars were primarily due to uptake rather than translocation.