Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.

The ecological and evolutionary mechanisms of antimicrobial resistance (AMR) emergence within patients and how these vary across bacterial infections are poorly understood. Increasingly widespread use of pathogen genome sequencing in the clinic enables a deeper understanding of these processes. In this Review, we explore the clinical evidence to support four major mechanisms of within-patient AMR emergence in bacteria: spontaneous resistance mutations; in situ horizontal gene transfer of resistance genes; selection of pre-existing resistance; and immigration of resistant lineages. Within-patient AMR emergence occurs across a wide range of host niches and bacterial species, but the importance of each mechanism varies between bacterial species and infection sites within the body. We identify potential drivers of such differences and discuss how ecological and evolutionary analysis could be embedded within clinical trials of antimicrobials, which are powerful but underused tools for understanding why these mechanisms vary between pathogens, infections and individuals. Ultimately, improving understanding of how host niche, bacterial species and antibiotic mode of action combine to govern the ecological and evolutionary mechanism of AMR emergence in patients will enable more predictive and personalized diagnosis and antimicrobial therapies.

Pseudomonas aeruginosa's adaptive trajectory: diverse origins, convergent paths.

Does genetic background contribute to populations following the same or divergent adaptive trajectories? A recent study by Filipow et al. evolved multiple genetically distinct Pseudomonas aeruginosa strains to an artificial cystic fibrosis lung sputum media. The strains adapted at different rates but converged on similar phenotypes despite their initial diversity.

Evolutionary innovation through transcription factor rewiring in microbes is shaped by levels of transcription factor activity, expression, and existing connectivity.

The survival of a population during environmental shifts depends on whether the rate of phenotypic adaptation keeps up with the rate of changing conditions. A common way to achieve this is via change to gene regulatory network (GRN) connections-known as rewiring-that facilitate novel interactions and innovation of transcription factors. To understand the success of rapidly adapting organisms, we therefore need to determine the rules that create and constrain opportunities for GRN rewiring. Here, using an experimental microbial model system with the soil bacterium Pseudomonas fluorescens, we reveal a hierarchy among transcription factors that are rewired to rescue lost function, with alternative rewiring pathways only unmasked after the preferred pathway is eliminated. We identify 3 key properties-high activation, high expression, and preexisting low-level affinity for novel target genes-that facilitate transcription factor innovation. Ease of acquiring these properties is constrained by preexisting GRN architecture, which was overcome in our experimental system by both targeted and global network alterations. This work reveals the key properties that determine transcription factor evolvability, and as such, the evolution of GRNs.

Evaluating the Utility of a Psychoeducational Serious Game (SPARX) in Protecting Inuit Youth From Depression: Pilot Randomized Controlled Trial.

BACKGROUND: Inuit youth in Northern Canada show considerable resilience in the face of extreme adversities. However, they also experience significant mental health needs and some of the highest adolescent suicide rates in the world. Disproportionate rates of truancy, depression, and suicide among Inuit adolescents have captured the attention of all levels of government and the country. Inuit communities have expressed an urgent imperative to create, or adapt, and then evaluate prevention and intervention tools for mental health. These tools should build upon existing strengths, be culturally appropriate for Inuit communities, and be accessible and sustainable in Northern contexts, where mental health resources are often scarce. OBJECTIVE: This pilot study assesses the utility, for Inuit youth in Canada, of a psychoeducational e-intervention designed to teach cognitive behavioral therapy strategies and techniques. This serious game, SPARX, had previously demonstrated effectiveness in addressing depression with Maori youth in New Zealand. METHODS: The Nunavut Territorial Department of Health sponsored this study, and a team of Nunavut-based community mental health staff facilitated youth's participation in an entirely remotely administered pilot trial using a modified randomized control approach with 24 youths aged 13-18 across 11 communities in Nunavut. These youth had been identified by the community facilitators as exhibiting low mood, negative affect, depressive presentations, or significant levels of stress. Entire communities, instead of individual youth, were randomly assigned to an intervention group or a waitlist control group. RESULTS: Mixed models (multilevel regression) revealed that participating youth felt less hopeless (P=.02) and engaged in less self-blame (P=.03), rumination (P=.04), and catastrophizing (P=.03) following the SPARX intervention. However, participants did not show a decrease in depressive symptoms or an increase in formal resilience indicators. CONCLUSIONS: Preliminary results suggest that SPARX may be a good first step for supporting Inuit youth with skill development to regulate their emotions, challenge maladaptive thoughts, and provide behavioral management techniques such as deep breathing. However, it will be imperative to work with youth and communities to design, develop, and test an Inuit version of the SPARX program, tailored to fit the interests of Inuit youth and Elders in Canada and to increase engagement and effectiveness of the program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05702086; https://www.clinicaltrials.gov/ct2/show/NCT05702086.

Enhancing an online cognitive behavioural therapy intervention for depression: Harnessing the feedback of sexual and gender minority youth to help improve SPARX.

OBJECTIVE: SPARX is an online cognitive behavioural therapy self-help intervention for adolescent depression provided in serious game format. Since 2014, it has been freely available in Aotearoa New Zealand (NZ) due to funding from the NZ government. In 2020/21, feedback from sexual and gender minority youth (SGMY) was used to refine and update SPARX. METHOD: Three online focus groups and follow-up email consultations involved 12 SGMY (16 to 25 years old) in NZ. A general inductive approach was used to analyse data. RESULTS: SGMY had specific needs as well as preferences and four themes were identified: attend to our contextual realities; portrayals of sexual and gender minority people in games; envisaged ideals for serious gaming and appraisals of SPARX. SGMY feedback was used to improve SPARX for this unique population, with the updates launched in October 2021. CONCLUSIONS: SGMY are underserved in terms of their mental health needs. Refining or tailoring existing interventions proffers a potential way forward in terms of addressing these needs.

Pre-hospital guidelines for CPR-Induced Consciousness (CPRIC): A scoping review.

Background: CPR-Induced Consciousness is an emerging phenomenon with a paucity of consensus guidelines from peak resuscitative bodies. Local prehospital services have had to implement their own CPR-Induced Consciousness guidelines. This scoping review aims to identify prehospital CPR-Induced Consciousness guidelines and compare or contrast their management options. Objective: The purpose of this scoping review is to identify and compare as many prehospital CPR-Induced Consciousness guidelines as feasible, highlight common management trends, and discuss the factors that might impact CPR-Induced Consciousness guidelines and the management trends identified. Design: To search for prehospital CPR-Induced Consciousness guidelines, a bibliographical search of five databases was undertaken (MEDLINE, EMBASE, Cochrane, Scopus, and CINAHL plus). Also included was a grey literature search arm, comprised of four search strategies: 1. Customised Google search, 2. Hand searching of targeted websites, 3. Grey literature databases, 4. Consultation with subject experts. Results: Our search extracted 23 prehospital CPR-Induced Consciousness guidelines and one good practise statement from the International Liaison Committee on Resuscitation. Of the 23 prehospital guidelines available, we identified 20 different ways of treating CPR-Induced Consciousness. Midazolam was the most frequently used drug to treat CPR-Induced Consciousness (14/23, 61%), followed by Ketamine (11/23, 48%) and Fentanyl (9/23, 39%). Conclusion: Prehospital CPR-Induced Consciousness guidelines are both exceptionally uncommon and vary substantially from each other. This has a flow-on effect towards data collection and only serves to continue CPR-Induced Consciousness's relatively unknown status surrounding both knowledge of, and the effect CPR-Induced Consciousness treatment has on cardiac arrest outcomes.

Novel multi jet fusion 3D-printed patient immobilization for radiation therapy.

PURPOSE: Thermoplastic immobilizers are used routinely in radiation therapy to achieve positioning accuracy. These devices are variable in quality as they are dependent on the skill of the human fabricator. We examine the potential multi jet fusion (MJF) 3D printing for the production immobilizers with a focus on the surface dosimetry of several MJF-printed PA12-based material candidates. Materials are compared with the goal of minimizing surface dose with comparison to standard thermoplastic. We introduce a novel metamaterial design for the shell of the immobilizer, with the aims of mechanical robustness and low-dose buildup. We demonstrate first examples of adult and pediatric cranial and head-and-neck immobilizers. METHODS: Three different PA12 materials were examined and compared to fused deposition modeling-printed polylactic acid (PLA), PLA with density lowered by adding hollow glass microspheres, and to perforated or perforated/stretched and solid status quo thermoplastic samples. Build-up dose measurements were made using a parallel plate chamber. A metamaterial design was established based on a packed hexagonal geometry. Radiochromic film dosimetry was performed to determine the dependence of surface dose on the metamaterial design. Full cranial and head-and-neck prototype immobilizers were designed, printed, and assessed with regard to dimensional accuracy. RESULTS: Build-up dose measurements demonstrated the superiority of the PA12 material with a light fusing agent, which yielded a ∼15% dose reduction compared to other MJF materials. Metamaterial samples provided dose reductions ranging from 11% to 40% compared to stretched thermoplastic. MJF-printed immobilizers were produced reliably, demonstrated the versatility of digital design, and showed dimensional accuracy with 97% of sampled points within ±2 mm. CONCLUSIONS: MJF is a promising technology for an automated fabrication of patient immobilizers. Material selection and metamaterial design can be leveraged to yield surface dose reduction of up to 40%. Immobilizer design is highly customizable, and the first examples of MJF-printed immobilizers demonstrate excellent dimensional accuracy.

Natural selection on crosstalk between gene regulatory networks facilitates bacterial adaptation to novel environments.

At the level of the gene, mutation is the raw material for natural selection. However, at the level of the gene regulatory network (GRN), variation is revealed to selection via promiscuous regulator activity ('crosstalk'), which creates opportunities for genetic innovation that can facilitate adaptation. Many genetic and environmental features can contribute to increasing potential for crosstalk by facilitating non-cognate interactions between regulatory elements. If a novel interaction provides a fitness benefit, rewired GRNs with strengthened affinity for newly forged connections can be selected. Here, we identify factors that facilitate opportunities for crosstalk and rewiring between GRNs, consider whether features of some GRNs make them more 'rewireable' than others and if these features might constrain evolution towards convergent outcomes. We explore patterns from laboratory and natural microbial populations that show changes within GRNs during adaptation. Finally, we discuss the prospects and open questions in the field.

Recruitment and Retention of Parents of Adolescents in a Text Messaging Trial (MyTeen): Secondary Analysis From a Randomized Controlled Trial.

BACKGROUND: Parenting programs are well established as an effective strategy for enhancing both parenting skills and the well-being of the child. However, recruitment for family programs in clinical and nonclinical settings remains low. OBJECTIVE: This study aims to describe the recruitment and retention methods used in a text messaging program (MyTeen) trial for parents of adolescents (10-15 years) and identify key lessons learned. We aim to provide insights and direction for researchers who seek to recruit parents and build on the limited literature on recruitment and retention strategies for parenting program trials. METHODS: A recruitment plan was developed, monitored, and modified as needed throughout the course of the project. Strategies to facilitate recruitment were identified (eg, program content and recruitment material, staff characteristics, and study procedures). Traditional and web-based recruitment strategies were used. RESULTS: Over a 5-month period, 319 parents or caregivers expressed interest in our study, of which 221 agreed to participate in the study, exceeding our recruitment target of 214 participants. Attrition was low at the 1-month (4.5% overall; intervention group: n=5, 4.6%; control group: n=5, 4.5%) and 3-month follow-ups (9% overall; intervention group: n=10, 9.2%; control group: n=10, 8.9%). CONCLUSIONS: The use of web-based recruitment strategies appeared to be most effective for recruiting and retaining parents in a text-messaging program trial. However, we encountered recruitment challenges (ie, underrepresentation of ethnic minority groups and fathers) similar to those reported in the literature. Therefore, efforts to engage ethnic minorities and fathers are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000117213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374307.

Implementing the Routine Use of Electronic Mental Health Screening for Youth in Primary Care: Systematic Review.

BACKGROUND: Adolescents often present at primary care clinics with nonspecific physical symptoms when, in fact, they have at least 1 mental health or risk behavior (psychosocial) issue with which they would like help but do not disclose to their care provider. Despite global recommendations, over 50% of youths are not screened for mental health and risk behavior issues in primary care. OBJECTIVE: This review aimed to examine the implementation, acceptability, feasibility, benefits, and barriers of e-screening tools for mental health and risk behaviors among youth in primary care settings. METHODS: Electronic databases-MEDLINE, CINAHL, Scopus, and the Cochrane Database of Systematic Reviews-were searched for studies on the routine screening of youth in primary care settings. Screening tools needed to be electronic and screen for at least 1 mental health or risk behavior issue. A total of 11 studies that were reported in 12 articles, of which all were from high-income countries, were reviewed. RESULTS: e-Screening was largely proven to be feasible and acceptable to youth and their primary care providers. Preconsultation e-screening facilitated discussions about sensitive issues and increased disclosure by youth. However, barriers such as the lack of time, training, and discomfort in raising sensitive issues with youth continued to be reported. CONCLUSIONS: To implement e-screening, clinicians need to change their behaviors, and e-screening processes must become normalized into their workflows. Co-designing and tailoring screening implementation frameworks to meet the needs of specific contexts may be required to ensure that clinicians overcome initial resistances and perceived barriers and adopt the required processes in their work.

Pseudomonas aeruginosa adapts to octenidine via a combination of efflux and membrane remodelling.

Pseudomonas aeruginosa is an opportunistic pathogen capable of stably adapting to the antiseptic octenidine by an unknown mechanism. Here we characterise this adaptation, both in the laboratory and a simulated clinical setting, and identify a novel antiseptic resistance mechanism. In both settings, 2 to 4-fold increase in octenidine tolerance was associated with stable mutations and a specific 12 base pair deletion in a putative Tet-repressor family gene (smvR), associated with a constitutive increase in expression of the Major Facilitator Superfamily (MFS) efflux pump SmvA. Adaptation to higher octenidine concentrations led to additional stable mutations, most frequently in phosphatidylserine synthase pssA and occasionally in phosphatidylglycerophosphate synthase pgsA genes, resulting in octenidine tolerance 16- to 256-fold higher than parental strains. Metabolic changes were consistent with mitigation of oxidative stress and altered plasma membrane composition and order. Mutations in SmvAR and phospholipid synthases enable higher level, synergistic tolerance of octenidine.

Endotracheal Tube Intracuff Pressure Changes in Patients Transported by a Helicopter Emergency Medical Service: A Prospective Observational Study.

OBJECTIVE: The pressure within an endotracheal tube cuff is of particular importance in helicopter emergency medical services (HEMS) transport because the unpressurized cabin is subjected to decreases in atmospheric pressure. This can cause the cuff to overinflate and may be associated with clinical complications. We sought to evaluate endotracheal tube cuff pressure changes among intubated patients during HEMS transport. METHODS: A prospective observational study was performed including adult patients who were intubated and transported by helicopter between April 2017 and October 2018. Cuff pressures were measured before, during, and after HEMS transport with a commercial manometer. RESULTS: A total of 208 patients were included. The median maximum flight altitude was 3,000 (interquartile range [IQR], 2,000-5,000) ft. The median initial cuff pressure before takeoff was 35 (IQR, 24-50) cm H2O, which increased to 50 (IQR, 35-70) cm H2O at maximum altitude. A total of 169 (81.3%) patients had a cuff pressure > 30 cm H2O at maximum altitude. There was a moderate correlation between altitude and cuff pressure (r = 0.532, P < .001). CONCLUSIONS: Cuff pressure increased during HEMS transport, demonstrating the need for routine cuff pressure monitoring during flight. Further research is required to determine if exposure to transient increases in cuff pressure for short durations is clinically significant.

Intersex adolescents seeking help for their depression: the case study of SPARX in New Zealand.

OBJECTIVE: SPARX is a computerized cognitive behavioral therapy self-help program for adolescent depression that is freely available in New Zealand. At registration, users identify themselves as either male, female, intersex, or transgender. We aimed to describe the mental health of adolescent intersex users. METHOD: A secondary analysis of SPARX usage data over 5 years. RESULTS: Of the 8922 adolescents users, 0.6% (n = 50) identified as intersex. Based on Patient Health Questionnaire 9 - modified for Adolescents (PHQ-A) results, 78.3% of intersex users had high levels of depression and/or self-harm and suicidal ideation. The mean PHQ-A scores for intersex users were significantly higher than for males and females (p < .001). As only three intersex users completed SPARX Level 4 or more (of the seven-level program), we were unable to meaningfully investigate any reductions in their depressive symptoms over time. CONCLUSIONS: There is a dearth of empirical data on the mental health of intersex adolescents. These results suggest that intersex adolescents seeking help from an online resource have high mental health needs compared with other young people, possibly because they defer seeking help.

Computerized cognitive behavioural therapy for gender minority adolescents: Analysis of the real-world implementation of SPARX in New Zealand.

OBJECTIVE: SPARX is a form of computerized cognitive behavioural therapy in serious game format funded via the Ministry of Health to be freely available in New Zealand. At registration users identify themselves as male, female, transgender or intersex. We aimed to establish whether adolescent transgender users of SPARX, compared to adolescent male and female users, were more likely to have high mental health needs at baseline and were more likely to complete SPARX. We also sought to determine changes in transgender adolescents' depressive symptoms after using SPARX. METHODS: Quantitative analysis of 5 years of usage data from the nation-wide delivery of SPARX in New Zealand. RESULTS: There were 9079 adolescents who completed the registration process and used SPARX, 2.3% (n = 207) identified as transgender. The majority of transgender registrants (69.0%) completing a baseline Patient Health Questionnaire - modified for Adolescents were categorized as having high mental health needs, significantly more so than male and female registrants (p < 0.001). Over half of all SPARX registrants completed the first module of the program, with subsequently lower proportions of transgender registrants completing Module 4 (p = 0.005) and Module 7 (i.e. the last module, p = 0.048). Of those registrants completing a baseline and subsequent Patient Health Questionnaire - modified for Adolescents, both male (n = 247) and female (n = 630) registrants, on average, had improvements in their scores (2.68 and 3.15, respectively), whereas transgender registrants (n = 14) did not (-0.43) (p = 0.048). CONCLUSION: This is the first study describing the impact of an e-therapy on transgender young people. The analysis of data from this free self-help intervention suggests that transgender adolescents seeking treatment for depression have particularly high mental health needs, and an existing well tested tool may be less effective for them than it is for others. Taken together the results appear to suggest targeted efforts may be required for transgender adolescents.

Revising Computerized Therapy for Wider Appeal Among Adolescents: Youth Perspectives on a Revised Version of SPARX.

Background: The way in which computerized therapy is presented may be important for its uptake. We aimed to explore adolescents' views on the appeal of a tested computerized cognitive behavioral therapy (CCBT) for depression (SPARX), and a revised version (SPARX-R). The versions were similar but while SPARX is presented explicitly as a treatment for depression, SPARX-R is presented as providing skills that could be useful for young people for when they were depressed, down, angry, or stressed. Methods: We held 9 focus groups with a total of 79 adolescents (13-19 years old; 47 females; 34 New Zealand European; 22 Maori or Pacific; 60 reported having experienced feeling down or low for at least several days in a row). Groups viewed the opening sequences of SPARX and SPARX-R (in random order), then took part in a semi-structured discussion and completed a brief questionnaire. Responses were analyzed using a general inductive approach. Results: Participants considered both SPARX and SPARX-R useful and considered the stated purpose of the program to be important. Four themes contrasted the two approaches. The first, "naming depression is risky", referred to perceptions that an explicit focus on depression could be off-putting, including for adolescents with depression. The second theme of "universality" reflected preferences for a universal approach as young people might not recognize that they were depressed, and all would benefit from the program. In contrast, "validation" reflected the view of a significant minority that naming depression could be validating for some. Finally, the theme of "choice" reflected a near-unanimously expressed preference for both options to be offered, allowing user choice. In questionnaire responses, 40 (68%) of participants preferred SPARX-R, 13 (18%) preferred SPARX, while 10 (14%) "didn't mind". Responses were similar among participants who reported that they had experienced at least a few days of low mood and those who had not. Conclusions: The way a CCBT program is presented may have implications for its appeal. The potential population impact of CCBT programs explicitly targeting depression and those targeting more universal feelings such as being stressed or feeling depressed should be explored for varied user groups.

Development of MyTeen Text Messaging Program to Support Parents of Adolescents: Qualitative Study.

BACKGROUND: Parents play an important role in the lives of adolescents, and supporting and addressing the needs of families continue to be the focus of many researchers and policy makers. Mobile health interventions have great potential for supporting parents at a population level because of their broad reach and convenience. However, limited evidence exists for such interventions for parents of adolescents. This study reports on the formative work conducted with parents and/or primary caregivers to identify their needs and preferences for the development of MyTeen-an SMS text messaging program on promoting parental competence and mental health literacy for parents of adolescents (aged 10-15 years). OBJECTIVE: The aim of this qualitative study was to explore parents and/or primary caregivers' perspectives around youth well-being, parenting, and parenting support and their input on the development of MyTeen SMS text messaging parenting intervention. METHODS: A total of 5 focus groups (n=45) were conducted with parents or primary caregivers of adolescents aged 10 to 15 years between October and December 2017 in New Zealand. A semistructured interview guideline and prompts were used. Data were audiotaped, transcribed, and analyzed using inductive thematic analysis. RESULTS: Participants were concerned about youth mental health (ie, stigma and increasing demand on adolescents), and a number of parenting challenges (ie, social expectations, time, impact of technology, changes in family communication pattern, and recognizing and talking about mental health issues) were noted. Importantly, participants reported the lack of services and support available for families, and many were not aware of services for parents themselves. A number of recommendations were given on the style, content, and frequency of developing the text messaging program. CONCLUSIONS: Findings from this qualitative work informed the development of MyTeen, an SMS text messaging program designed to increase parental competence and improve mental health literacy for parents of adolescents.

Effect of MyTeen SMS-Based Mobile Intervention for Parents of Adolescents: A Randomized Clinical Trial.

Importance: There is global pressure to respond to the burden posed by adolescent mental health problems. The National Mental Health Commission has made a call for investment in mobile health services directed at prevention and early intervention to relieve the demand on targeted mental health services that are costly to provide. Parents and primary caregivers play a significant role in the lives of adolescents and are important targets for such efforts. Currently, there is no evidence for the effectiveness of programs delivered solely via text message for parents of adolescents. Objective: To evaluate the effects of a text-messaging program (MyTeen) on promoting parental competence and mental health literacy for parents of adolescents. Design, Setting, and Participants: A parallel 2-group randomized clinical trial was conducted in New Zealand. A total of 221 parents and primary caregivers of adolescents aged 10 to 15 years were recruited from March 19 to August 17, 2018, via community outreach and social media and were randomly allocated 1:1 into the control or the intervention group. Statistical analysis was performed on the principle of intention to treat with adjustment for baseline factors and ethnicity. Intervention: A text-messaging program for parents of adolescents (age 10-15 years) to promote parental competence and mental health literacy. Participants received 1 daily text message over 4 weeks. Main Outcomes and Measures: Parental competence, assessed at 1 month after randomization by the Parenting Sense of Competence Scale. Results: In total, 221 participants (214 [96.8%] female) were randomized, 109 to the intervention group and 112 to the control group; 201 participants (91%) completed the trial at 3 months. Significant group difference was observed on the primary outcome at the end of 1 month of intervention, with participants reporting a higher level of parental competence than those in the control group (estimated mean difference, 3.33 points; 95% CI, 1.37-5.29 points; P = .002). Except for knowledge about mental health, all secondary outcomes were significant, including continued improvement in parental competence at 3 months (estimated mean difference, 4.08 points; 95% CI, 1.96-6.20 points; P < .001), knowledge of help seeking (estimated mean difference, 0.99 points; 95% CI, 0.49-1.50 points; P < .001), parental distress (estimated mean difference, -2.39 points; 95% CI, -4.37 to -0.40 points; P = .02), and parent-adolescent communication (estimated mean difference, 2.21 points; 95% CI, 0.48-3.95 points; P = .01), with participants in the intervention group reporting better parenting-related outcomes than the control group at 1 and 3 months after the intervention. Conclusions and Relevance: This text-messaging program for parents of adolescents appears to be an effective and feasible way to facilitate the implementation and delivery of evidence-based information to populations that are not easily reached with other intervention modalities. The program can be easily scaled up for delivery as an early preventive intervention and may represent a less expensive option for service delivery. Trial Registration: anzctr.org.au Identifier: ACTRN12618000117213.

Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc.

BACKGROUND: In molecular imaging and nuclear medicine, theranostic agents that integrate radionuclide pairs are successfully being used for individualized care, which has led to rapidly growing interest in their continued development. These compounds, which are radiolabeled with one radionuclide for imaging and a chemically identical or similar radionuclide for therapy, may improve patient-specific treatment and outcomes by matching the properties of different radionuclides with a targeting vector for a particular tumor type. One proposed theranostic radionuclide is scandium-47 (47Sc, T1/2 = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, 43Sc (T1/2 = 3.89 h) and 44Sc (T1/2 = 3.97 h) for imaging. The aim of this study was to investigate the photonuclear production of 47Sc via the 48Ti(γ,p)47Sc reaction using an electron linear accelerator (eLINAC), separation and purification of 47Sc, the radiolabeling of somatostatin receptor-targeting peptide DOTATOC with 47Sc, and in vitro receptor-mediated binding of [47Sc]Sc-DOTATOC in AR42J somatostatin receptor subtype two (SSTR2) expressing rat pancreatic tumor cells. RESULTS: The rate of 47Sc production in a stack of natural titanium foils (n = 39) was 8 × 107 Bq/mA·h (n = 3). Irradiated target foils were dissolved in 2.0 M H2SO4 under reflux. After dissolution, trivalent 47Sc ions were separated from natural Ti using AG MP-50 cation exchange resin. The recovered 47Sc was then purified using CHELEX 100 ion exchange resin. The average decay-corrected two-step 47Sc recovery (n = 9) was (77 ± 7)%. A radiolabeling yield of > 99.9% of [47Sc]Sc-DOTATOC (0.384 mg in 0.3 mL) was achieved using 1.7 MBq of 47Sc. Blocking studies using Octreotide illustrated receptor-mediated uptake of [47Sc]Sc-DOTATOC in AR42J cells. CONCLUSIONS: 47Sc can be produced via the 48Ti(γ,p)47Sc reaction and separated from natural Ti targets with a yield and radiochemical purity suitable for radiolabeling of peptides for in vitro studies. The data in this work supports the potential use of eLINACs for studies of photonuclear production of medical radionuclides and the future development of high-intensity eLINAC facilities capable of producing relevant quantities of carrier-free radionuclides currently inaccessible via routine production pathways or limited due to costly enriched targets.