Three Is a Magic Number: Tailored Clickable Chelators Used to Determine Optimal RGD-Peptide Multiplicity in αvβ6-Integrin Targeted Lu-Labeled Cancer Theranostics.

The cellular adhesion receptor αvβ6-integrin is highly expressed in many cancers, e.g., pancreatic, lung, head-and-neck, cervical, bladder, and esophageal carcinoma.

A Description of the Dental Health and Treatment of Ukraine Military at U.S. Army Clinics in Germany.

Introduction: Since the start of the Russo-Ukrainian war, most reports have focused on trauma and combat conditions. Trauma care is essential; however, disease and nonbattle injuries (DNBIs) also burden armies and reduce combat effectiveness. Dental emergencies (DEs) account for a substantial portion of DNBI, but there is limited information on Ukrainian military dental readiness.

The importance of tyrosines in multimers of cyclic RGD nonapeptides: towards αvβ6-integrin targeted radiotherapeutics.

In a recent paper in this journal (, 2023, , 2429), we described an unusually strong impact of regiospecific exchange of phenylalanines by tyrosines in 10 gallium-68-labeled trimers of certain cyclic RGD peptides, c[XRGDLAXp(Me)K] (X = F or Y), on non-specific organ uptakes. We found that there was, in part, no correlation of liver uptake with established polarity proxies, such as the octanol-water distribution coefficient (log ). Since this observation could not be explained straightforwardly, we suggested that the symmetry of the compounds had resulted in a synergistic interaction of certain components of the macromolecules.

Potential Efficacy of 68 Ga-Trivehexin PET/CT and Immunohistochemical Validation of αvβ6 Integrin Expression in Patients With Head and Neck Squamous Cell Carcinoma and Pancreatic Ductal Adenocarcinoma.

Purpose: αvβ6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized αvβ6 integrin selective nonapeptide, which can be labeled with a positron emitter like 68 Ga. This is a pilot study to assess the potential role of 68 Ga-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with αvβ6 integrin expression by the tumor tissue on immunohistochemistry (IHC).

Efficiency of succinylated gelatin and amino acid infusions for kidney uptake reduction of radiolabeled αvβ6-integrin targeting peptides: considerations on clinical safety profiles.

Purpose: Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvβ6-integrin for PET imaging of carcinomas. Lu-D0301 is a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability.

Comparison of Dental Emergencies Among U.S. Military and Civilian Personnel During Combat Operations in 2007-2009.

Introduction: Information from published studies describing dental treatment of nonmilitary personnel in a military theater of operations is sparse. The primary objective of this study is to determine the number of dental emergencies (DEs) and the types of dental treatment rendered on non-U.S.

In-House Preparation and Quality Control of Ac-225 Prostate-Specific Membrane Antigen-617 for the Targeted Alpha Therapy of Castration-Resistant Prostate Carcinoma.

Purpose: Ac-225 labeled with prostate-specific membrane antigen (PSMA-617), a transmembrane glycoprotein which is highly expressed in prostate carcinoma cells, is presently being considered a promising agent of targeted alpha therapy for the treatment of patients suffering from metastatic castration-resistant prostate cancer. In the present study, we report an optimized protocol for the preparation of therapeutic dose of Ac-225 PSMA-617 with high yield and radiochemical purity (RCP).

Methods: Ac-225 PSMA-617 was prepared by adding the peptidic precursor-PSMA-617 (molar ratios, Ac-225: PSMA-617 = 30:1) in 1 ml ascorbate buffer to Ac-225 and heating the reaction mixture at 90°C for 25 min to obtain the radiopeptide with high RCP and yield.

Radiation Exposure to the Nuclear Medicine Personnel During Preparation and Handling of Bi-Radiopharmaceuticals.

Because of the excellent ability of α-particles to transfer a high amount of energy over a short tissue range, targeted α-therapy has been attracting rising numbers of nuclear medicine centers. In this study, we estimated the radiation exposure to the occupational workers with pocket dosimeters during handling of the α-emitter Bi, used for targeted α-therapy of neuroendocrine tumor and castration-resistant prostate cancer patients. The dose rates from patients at different distances and time points after injection of the therapy were also evaluated.

Advancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development, Molecular Imaging and Applied Diagnostics; March 14-16, 2018; Vienna, Austria.

Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches.

Longitudinal Analysis of CAD/CAM Restoration Incorporation Rates into Navy Dentistry.

Introduction: Computer-aided design/computer-aided manufacturing (CAD/CAM) has gained increasing popularity since the first commercially viable dental system was introduced in the mid-1980s. Digitally milled dental restorations can be fabricated chairside in the course of one dental appointment, reducing time, cost, and manpower when compared with traditional laboratory-fabricated analog restorations. Clinical performance, physical properties, and esthetics of digital restorations have been shown to be comparable to traditional analog restorations.

Efficient formation of inert Bi-213 chelates by tetraphosphorus acid analogues of DOTA: towards improved alpha-therapeutics.

Background: The recently growing interest in targeted alpha-therapy (TAT) calls for improvement of the labelling chemistry of the corresponding radionuclides. Bi is a short-lived alpha emitter which emits only one alpha particle in its decay chain. Hence, it might be safer in application than other respective nuclides, such as Ra or Ac, because no alpha-emitting daughters are released upon recoil.

Causes of Oral-Maxillofacial Injury of U.S. Military Personnel in Iraq and Afghanistan, 2001-2014.

Background: Few studies have examined the causes or mechanisms of oral-maxillofacial (OMF) injury among deployed military populations. This study reports causes of OMF injuries to U.S.

Oral-Maxillofacial Injury Surveillance of U.S. Military Personnel in Iraq and Afghanistan, 2001 to 2014.

Background: Cranial and oral-maxillofacial injuries accounted for 33% of military visits to in-theater (Level III) military treatment facilities for battle injuries during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Even after years of conflict, the size and scope of oral-maxillofacial injuries in military armed conflict is still not fully understood. This study reports U.

The influence of the combination of carboxylate and phosphinate pendant arms in 1,4,7-triazacyclononane-based chelators on their 68Ga labelling properties.

In order to compare the coordination properties of 1,4,7-triazacyclononane (tacn) derivatives bearing varying numbers of phosphinic/carboxylic acid pendant groups towards 68Ga, 1,4,7-triazacyclononane-7-acetic-1,4-bis(methylenephosphinic) acid (NOPA) and 1,4,7- triazacyclononane-4,7-diacetic-1-[methylene(2-carboxyethyl)phosphinic] acid (NO2AP) were synthesized using Mannich reactions with trivalent or pentavalent forms of H-phosphinic acids as phosphorus components. Stepwise protonation constants logK1-3 12.06, 3.

Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer.

Background: Due to its high expression in prostate cancer, PSMA (prostate-specific membrane antigen) represents an ideal target for both diagnostic imaging and endoradiotherapeutic approaches. Based on a previously published highly specific PSMA ligand ([(68)Ga]DOTA-FFK(Sub-KuE)), we developed a corresponding metabolically stable 1,4,7,10-tetraazacyclododececane,1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) construct for theranostic treatment of prostate cancer.

Methods: All ligands were synthesized by a combined solid phase and solution phase synthesis strategy.

68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies.

Unlabelled: On the basis of the high and consistent expression of prostate-specific membrane antigen (PSMA) in metastatic prostate cancer (PC), the goal of this study was the development, preclinical evaluation, and first proof-of-concept investigation of a PSMA inhibitor for imaging and therapy (PSMA I&T) for (68)Ga-based PET and (177)Lu-based endoradiotherapeutic treatment in patients with metastatic and castration-resistant disease.

Methods: PSMA I&T was synthesized in a combined solid phase and solution chemistry strategy. The PSMA affinity of (nat)Ga-/(nat)Lu-PSMA I&T was determined in a competitive binding assay using LNCaP cells.

MA-NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules.

In the past few years, gallium-68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA-NOTMP), a new C-functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for (68) Ga (low ligand concentration, labelling at low pH even at room temperature). A "ready-to-be-grafted" bifunctional chelating agent (p-NCS-Bz-MA-NOTMP) was prepared to allow (68) Ga labelling of sensitive biological vectors.

Medical evacuation of French forces for dental emergencies: Operation Serval.

Objectives: The objectives of this study were to (1) quantify the number of intratheater dental Medical evacuations (MEDEVACs) required for French Soldiers in Mali during Operation Serval and (2) determine a Soldier's time away from their unit because of MEDEVAC, dental treatment, and return to unit.

Methods: Data concerning MEDEVACs occurring during Operation Serval were recorded by the Patient Evacuation Coordination Center. MEDEVACs resulting from oral/facial/dental conditions were evaluated for the period from February 15, 2013 to May 15, 2013.

Risk of dental disease non-battle injuries and severity of dental disease in deployed U.S. Army personnel.

Dental Disease and Non-Battle Injuries (D-DNBI) continue to be a problem among U.S. Army active duty (AD), U.

Twins in spirit - episode I: comparative preclinical evaluation of [(68)Ga]DOTATATE and [(68)Ga]HA-DOTATATE.

Background: Recently, an intra-patient comparison demonstrated that the somatostatin (sst) ligand [(68)Ga]HA-DOTATATE ([(68)Ga]DOTA-3-iodo-Tyr(3)-octreotate) provides PET images comparable to or superior to those obtained with [(68)Ga]DOTATATE. To provide a comprehensive basis for nevertheless observed slight differences in tracer biodistribution and dosimetry, the characteristics of [(68)Ga]HA-DOTATATE were investigated in a detailed preclinical study.

Methods: Affinities of (nat)Ga-HA-DOTATATE and (nat)Ga-DOTATATE to sst1-5 were determined using membrane preparations and [(125)I]SST-28 as radioligand.

Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging.

Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy.

The incidence of dental disease nonbattle injuries in deployed U.S. Army personnel.

Background: In the past, the U.S. Army Reserve (USAR) and Army National Guard (ARNG) have exhibited lower levels of medical and dental readiness than active duty (AD) Soldiers when activated for deployment.