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Figure S11: Antitumor activity of [225Ac]DOTA-YS5 in subcutaneous DU145 tumors in nude mice. Tumor volume, survival analysis, and weight measurements after the injections of [225Ac]DOTA-YS5 in DU145 xenografts (n=6).

Supplementary Data: Methods and tables.

The place-based regional industrial strategies provide a novel approach to examining the role of science parks in enhancing regional innovation with place-based policies. With qualitative interviews and case analyses, this study investigates how a place-based science park affects innovation activities of technology-focused companies. Our research findings demonstrate paradoxical nature with both positive and negative aspects of firms’ strategies that cope with obstacles such as the lack of funding for R&D and weak policy on IP protection. These obstacles hinder the collaboration on innovation and strengthen the effect of economic uncertainty on companies’ short-term survival orientation. Important implications for both theory and practice are discussed with possible future research directions identified. JEL Classification: O32, M10, M38

Purpose:Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody–drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody.Experimental Design:[225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity.Results:Biodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line–derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 μCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi.Conclusions:[225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen–positive and prostate-specific membrane antigen–deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer.

The relationship between regional innovation and foreign direct investment (FDI) has been extensively examined, but the impact of regional innovation on FDI retention has received scant attention. Drawing on the logic of place-based approaches, the paper investigates this impact by conducting survival analyses on data collected across 31 provinces of China. We find that regional technician supply (RTS) and regional intellectual property flexibility (RIPF) help regions retain foreign ventures. However, RTS is less likely to retain the foreign investments of multinational enterprises with large research and development expenditure, while RIPF is more likely to retain them. Theoretical and policy implications are discussed. Refereed/Peer-reviewed

We extend the internationalization process literature by theorizing how institutional unpredictability and its changes can affect the foreign exit−reentry process and how the multidimensionality of foreign ownership can alter these impacts as a firm's conduit to different foreign countries. Drawing on the dynamic institution-based view, we examine a process whereby firms exit and reenter foreign countries in response to institutional dynamism. By distinguishing foreign shareholders from host and nonhost foreign countries, we identify the negative moderation effects of host-country foreign ownership but not nonhost foreign ownership. Our study, therefore, contributes an integrative framework to the de- and re- internationalization research. Refereed/Peer-reviewed

Radiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. Our radiolabeled antibody retains binding efficacy and shows a high tumor to background ratio in PCa xenografts. Furthermore, we show that radiolabeled antibody was able to suppress the growth of cell-derived and patient-derived xenografts, including PSMA-positive and deficient models. Nephrotoxicity, not seen at low radioactive doses, is evident at higher radioactivity dose levels, likely due to redistribution of daughter isotope213Bi. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46 targeted radioligand therapy in PCa.

Lymphocytes and innate immune cells are key drivers of multiple sclerosis (MS) and are the main target of MS disease modifying therapies (DMT). Ex vivo analyses of MS lesions have revealed cellular heterogeneity and variable T-cell levels, which may have important implication for patient stratification and choice of DMT. Although magnetic resonance imaging (MRI) has proven valuable to monitor DMT efficacy, its lack of specificity for cellular subtypes highlights the need for complementary methods to improve lesion characterization. Here, we evaluated the potential of 2’-deoxy-2’-[18F]fluoro-9-β-D-arabinofuranosylguanine (18F-FAraG) PET imaging to non-invasively assess infiltrating T-cells and to provide, in combination with MRI, a novel tool to determine lesion types. Methods: We used a novel MS mouse model that combines cuprizone and experimental autoimmune encephalomyelitis (EAE) to reproducibly induce two brain inflammatory lesion types, differentiated by their T-cell content. 18F-FAraG PET imaging, T2-weighted MRI, and T1-weighted contrast-enhanced MRI were performed prior to disease induction, during demyelination with high levels of innate immune cells, and following T-cell infiltration. Fingolimod immunotherapy was used to evaluate the ability of PET and MRI to detect therapy response. Ex vivo immunofluorescence analyses for T-cells, microglia/macrophages, myelin and blood brain barrier (BBB) integrity were performed to validate the in vivo findings. Results:18F-FAraG signal was significantly increased in brain and spinal cord at the time point of T-cell infiltration. 18F-FAraG signal from white matter (corpus callosum), and grey matter (cortex, hippocampus) further correlated with T-cell density. T2-weighted MRI detected white matter lesions independently of T-cells. T1-weighted contrast-enhanced MRI indicated BBB disruption at the time point of T-cell infiltration. Fingolimod treatment prevented motor deficits and decreased T-cell and microglia/macrophage levels. In agreement, 18F-FAraG signal was decreased in brain and spinal cord of Fingolimod-treated mice, T1-weighted contrast-enhanced MRI revealed intact BBB, while T2-weighted MRI remained unchanged. Conclusion: The combination of MRI and 18F-FAraG PET enables detection of inflammatory demyelination and T-cell infiltration in a MS mouse model, providing a new way to evaluate lesion heterogeneity during disease progression and following DMT. Upon clinical translation, these methods hold great potential for patient stratification, monitoring MS progression and therapy responses.

Previous research has identified a distinction between the internationalization of emerging market multinational enterprises (EMNEs) and their advanced-economy counterparts. However, the question as to whether EMNEs conduct outward foreign direct investment (OFDI) in a uniform manner remains under-studied. Prior studies have grouped together all emerging markets but have ignored the essential heterogeneity of EMNEs that leads to their diverse OFDI patterns and behaviours. In this study, we illustrate the drivers and related phenomena of heterogeneity by exploring differences and similarities between Chinese and Indian MNEs’ OFDI activities, namely, investment destinations (i.e., advanced vs. emerging economies), the level of political relationships with host countries, industry sectors supported by institutional patronage, and the primary motivations of investment projects. We suggest that the heterogeneity in OFDI is the result of the institutional environment and the strategic priorities of the industry sector. Refereed/Peer-reviewed

Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide

Lymphocytes and innate immune cells are key drivers of multiple sclerosis (MS) and are the main target of MS disease-modifying therapies (DMT). Ex vivo analyses of MS lesions have revealed cellular heterogeneity and variable T cell levels, which may have important implications for patient stratification and choice of DMT. Although MRI has proven valuable to monitor DMT efficacy, its lack of specificity for cellular subtypes highlights the need for complementary methods to improve lesion characterization. Here, we evaluated the potential of 2'-deoxy-2'