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Introduction: Single domain antibody fragments (sdAbs) are an appealing scaffold for radiopharmaceutical development due to their small size (~15 kDa), high solubility, high stability, and excellent tumor penetration. Previously, we developed NB7 sdAb, which has very high affinity for an epitope on PSMA that is different from those targeted by small molecule PSMA inhibitors. Herein, we evaluated NB7 after radioiodination using [*I]SGMIB (1,3,4-isomer) and iso-[*I]SGMIB (1,3,5-isomer), as well as their 211 At-labeled analogues., Methods: [*I]SGMIB, iso-[*I]SGMIB, [ 211 At]SAGMB, and iso-[ 211 At]SAGMB conjugates of NB7 sdAb were synthesized and their binding affinity, cell uptake and internalization were assessed in PSMA + PC3 PIP and PSMA - PC3 flu cells. Biodistribution studies were performed in mice bearing PSMA + PC3 PIP xenografts. First, a single-label experiment evaluated the tissue distribution of a NB7 bearing a His 6 -tag (NB7H6) and labeled with iso-[ 125 I]SGMIB. Three paired-label experiments then were performed to compare: a) NB7 labeled using [*I]SGMIB and iso-[*I]SGMIB, b) 131 I- vs 211 At-labeled NB7 conjugates and c) [ 125 I]SGMIB-NB7H6 to the small molecule PSMA inhibitor [ 131 I]YF2., Results: All NB7 radioconjugates bound specifically to PSMA with dissociation constants, K d , in the low nM range (1.4-6.4 nM). An initial biodistribution study demonstrated good tumor uptake for iso-[ 125 I]SGMIB-NB7H6 (7.2 ± 1.5 % ID/g at 1 h) and no deleterious effect of the His 6 -tag on renal activity levels, which declined to 3.1 ± 1.1 % ID/g by 4 h. Paired-label biodistribution found no distinction between the two SGMIB isomer NB7 conjugates with the [ 131 I]SGMIB-NB7-to-iso-[ 125 I]SGMIB-NB7 tumor uptake ratios not significantly different from unity: 1.06 ± 0.08 at 1 h, 1.04 ± 0.12 at 4 h, and 1.07 ± 0.09 at 24 h. Both isomer conjugates cleared rapidly from normal tissues and exhibited very low uptake in thyroid, lacrimal and salivary glands. Paired-label biodistribution of [ 131 I]SGMIB-NB7H6 and [ 211 At]SAGMB-NB7H6 demonstrated similar tumor uptake and kidney clearance for the two radioconjugates. However, levels of 211 At in thyroid, stomach, salivary and lacrimal glands were significantly higher (P < 0.05) that those for 131 I suggesting greater dehalogenation for [ 211 At]SAGMB-NB7H6. Finally, co-administration of [ 125 I]SGMIB-NB7H6 and [ 131 I]YF2 demonstrated good tumor uptake for both with considerably more rapid renal clearance for the NB7 radioconjugate., Conclusion: NB7 radioconjugates exhibited good accumulation in PSMA-positive xenografts with rapid clearance from kidney and other normal tissues. We conclude that NB7 is a potentially useful scaffold for developing PSMA-targeted theranostics with different characteristics than current small molecule and antibody-based approaches., Competing Interests: Declaration of competing interest LR and NP have filed a patent application that includes the NB7 single domain antibody fragment. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Educational attainment is a critical social determinant of health that impacts the risk and severity of incident ischaemic stroke, but less is known of its impact on intracerebral haemorrhage (ICH). The objective of this study is to determine whether educational attainment is associated with ICH severity and short-term prognosis., Methods: Subjects were enrolled in a prospectively ascertained cohort with primary ICH from 1994 to 2020 at Massachusetts General Hospital. Educational attainment, medical history of ICH risk factors, ICH volume and ICH score were obtained on admission. The primary outcomes were ICH volume and the ICH score., Results: Of 2539 eligible patients eligible, the median age of the sample was 74 (IQR 64-82) and 2159 (85%) had high school-only education. 1655 (65%) presented with an ICH volume less than or equal to 30 mL and 1744 (69%) presented with an ICH score less than 3. In multivariable logistic regression analyses controlling for age, income, employment history and prestroke diagnoses of hypertension and coronary artery disease, patients with high school-only education were more likely to have an ICH volume greater than 30 mL compared with college diplomates (OR 1.58, 95% CI 1.24 to 2.08) and more likely to have an ICH score of 3 or greater compared with college diplomates (OR 2.37, 95% CI 1.77 to 3.19)., Discussion: Prestroke educational attainment is independently associated with ICH severity and short-term prognosis, with lower educational attainment associated with larger ICH volumes and higher ICH scores. Future studies should examine how educational attainment impacts exposure to traditional clinical risk factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)