Thermoluminescent dosimeters (TLD-100) for absorbed dose measurements in alpha-emitting radionuclides.

Early works that used thermoluminescent dosimeters (TLDs) to measure absorbed dose from alpha particles reported relatively high variation (10%) between TLDs, which is undesirable for modern dosimetry applications. This work outlines a method to increase precision for absorbed dose measured using TLDs with alpha-emitting radionuclides by applying an alpha-specific chip factor (CF) that individually characterizes the TLD sensitivity to alpha particles. Variation between TLDs was reduced from 21.8% to 6.7% for the standard TLD chips and 7.9% to 3.3% for the thin TLD chips. It has been demonstrated by this work that TLD-100 can be calibrated to precisely measure the absorbed dose to water from alpha-emitting radionuclides.

Kapok fiber composites minimizing secondary waste and disposal costs for large-scale radioactive liquid treatment.

Conventional liquid treatments for large-scale, low-level radioactive wastewater, such as ion exchange and waste solidification, face challenges due to the large amounts of secondary waste and high disposal costs. A new large-scale decontamination method is proposed that uses kapok fiber composites for rapid radionuclide adsorption and high volume reduction to minimize secondary waste. The composite consists of natural zeolite and kapok holocellulose, which has high water-soaking ability and low-temperature pyrolysis. The kapok composites, fabricated using a commercial wet-laid nonwoven manufacturing process, absorbs 99% of low-level radioactive cesium in 20 min, reducing the volume by 98% and the weight by 47% at 300 °C. The low-temperature pyrolysis process below 300 °C prevents cesium desorption and gasification by avoiding zeolite destruction. The mass-producible kapok composites can be used for adsorbing various radionuclides in large-scale wastewater by attaching specific adsorbents for target isotopes to the composites.

Assessment of radio-activation using spectroscopy in medical linear accelerators.

In radiotherapy, when photon energy exceeding 8 MV is utilized, photoneutrons can activate the components within the gantry of the linear accelerator (linac). At the end of the linac's lifecycle, radiation workers are tasked with its dismantling and disposal, potentially exposing them to unintentional radiation. This study aims to identify and measure the radioisotopes generated by this activation through spectroscopy, and to evaluate the effective dose rate. We selected nine medical linacs, considering various factors such as manufacturer (Siemens, Varian, and Elekta), model, energy, period of operation, and workload. We identified the radionuclides in the linac head by employing an in situ high-purity germanium (HPGe) detector. Spectroscopy and dose-rate measurements were conducted post-shutdown. We also measured the dose rates at the beam-exit window following irradiation with 10 MV and 15 MV photon beams. As a result of the spectroscopy, we identified approximately 20 nuclides including those with half-lives of 100 days or longer, such as 54Mn, 60Co, 65Zn, 122Sb, and 198Au. The dose rate measurements after 10 MV irradiation decreased to the background level in 10 min. By contrast, on 15 MV irradiation, the dose rate was 628 nSv/h after 10 min and decreased to 268 nSv/h after 1.5 hours. It was confirmed that the difference in the level of radiation and the type of nuclide depends on the period of use, energy, and workload. However, the type of nuclide does not differ significantly between the linacs. It is necessary to propose appropriate guidelines for the safety of workers, and disposal/move-install should be planned while taking into consideration the equipment's energy usage rate.

An Evaluation of the Edible Value of Salvia miltiorrhiza Seeds: Proximate Composition, Phytochemical Components and Antioxidant Activity.

Salvia miltiorrhiza seeds (SMS) are the main by-product of the production processing of Radix Salviae Miltiorrhizae. The main purposes of this work are to analyse the nutritional components in SMS, to explore the antioxidant activity of the chemical components in SMS and to evaluate the possibility of SMS as a raw material for functional foods. The contents of crude fibre, total protein, carbohydrates, total phenolics and flavonoids in SMS and the composition and relative content of fatty acids in SMS oil were determined. The results suggested that SMS has high contents of crude fibre (28.68 ± 4.66 g/100 g), total protein (26.65 ± 2.51 g/100 g), total phenolics (6.45 ± 0.55 mg of gallic acid equivalent/g) and total flavonoids (3.28 ± 0.34 mg of rutin equivalent/g), as well as a high level of α-linolenic acid (33.774 ± 4.68%) in their oil. Twenty-two secondary metabolites were identified in SMS residue, and nine compounds were isolated. The IC50 values of the total phenolic content in SMS on an ABTS radical, DPPH radical, superoxide radical and hydroxyl radical were 30.94 ± 3.68 µg/mL, 34.93 ± 4.12 µg/mL, 150.87 ± 17.64 µg/mL and 230.19 ± 24.47 µg/mL, respectively. The results indicate that SMS contain many nutrients and have high utilization value as a promising functional food.

Functional expression, purification, biochemical and biophysical characterizations, and molecular dynamics simulation of a histidine acid phosphatase from Saccharomyces cerevisiae.

A histidine acid phosphatase (HAP) (PhySc) with 99.50% protein sequence similarity with PHO5 from Saccharomyces cerevisiae was expressed functionally with the molecular mass of ∼110 kDa through co-expression along with the set of molecular chaperones dnaK, dnaJ, GroESL. The purified HAP illustrated the optimum activity of 28.75 ± 0.39 U/mg at pH 5.5 and 40 ˚C. The Km and Kcat values towards calcium phytate were 0.608 ± 0.09 mM and 650.89 ± 3.6 s- 1. The half-lives (T1/2) at 55 and 60 ˚C were 2.75 min and 55 s, respectively. The circular dichroism (CD) demonstrated that PhySc includes 30.5, 28.1, 21.3, and 20.1% of random coils, α-Helix, ß-Turns, and ß-Sheet, respectively. The Tm recorded by CD for PhySc was 56.5 ± 0.34˚C. The molecular docking illustrated that His59 and Asp322 act as catalytic residues in the PhySc. MD simulation showed that PhySc at 40 ˚C has higher structural stability over those of the temperatures 60 and 80 ˚C that support the thermodynamic in vitro investigations. Secondary structure content results obtained from MD simulation indicated that PhySc consists of 34.03, 33.09, 17.5, 12.31, and 3.05% of coil, helix, turn, sheet, and helix310, respectively, which is almost consistent with the experimental results.

Exploring the role of combined external beam radiotherapy and targeted radioligand therapy with [177Lu]Lu-PSMA-617 for prostate cancer - from bench to bedside.

Management of prostate cancer (PC) might be improved by combining external beam radiotherapy (EBRT) and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with lutetium-177 (177Lu)-labeled PSMA inhibitors. We hypothesized a higher efficacy of the combination due to augmentation of the radiation dose to the tumor and interactions of EBRT with PSMA expression potentially increasing radiopharmaceutical uptake. Therefore, this study analyzed the influence of radiation on PSMA expression levels in vitro. The results were translated to evaluate the efficacy of the combination of photon EBRT and [177Lu]Lu-PSMA-617 in a murine PC xenograft model. Finally, a clinical case report on a combined elective field EBRT with RLT dose escalation illustrates a proof-of-concept. Methods: PSMA gene and protein expression were assessed in human PSMA-overexpressing LNCaP cells after irradiation using reverse transcription quantitative polymerase chain reaction (RT-qPCR), flow cytometry and On-Cell Western assays. In the in vivo therapy study, LNCaP tumor-bearing BALB/c nu/nu mice were irradiated once with 2 Gy X-ray EBRT and injected with 40 MBq [177Lu]Lu-PSMA-617 after 4 h or received single or no treatment (n = 10 each). Tumor-absorbed doses by [177Lu]Lu-PSMA-617 were calculated according to the Medical Internal Radiation Dosimetry (MIRD) formalism after deriving time-activity curves using a gamma probe. An exemplified patient case is demonstrated where fractionated EBRT (54 Gy to prostate; 45 Gy to pelvic lymphatics) and three cycles of [177Lu]Lu-PSMA-617 (3.4-6.0 GBq per cycle) were sequentially combined under concurrent androgen deprivation for treating locally advanced PC. Results: At 4 h following irradiation with 2-8 Gy, LNCaP cells displayed a PSMA protein upregulation by around 18% relative to non-irradiated cells, and a stronger upregulation on mRNA level (up to 2.6-fold). This effect was reversed by 24 h when PSMA protein levels were downregulated by up to 22%. Mice treated with the combination therapy showed significantly improved outcomes regarding tumor control and median survival (p < 0.0001) as compared to single or no treatment. Relative to monotherapy with PSMA-RLT or EBRT, the tumor doubling time was prolonged 1.7- or 2.7-fold and the median survival was extended by 24% or 60% with the combination, respectively. Additionally, tumors treated with EBRT exhibited a 14% higher uptake of the radiopharmaceutical as evident from the calculated tumor-absorbed dose, albeit with high variability in the data. Concerning the patient case, the tri-modality treatment was well tolerated and the patient responded with a long-lasting complete biochemical remission for five years following end of PSMA-RLT. The patient then developed a biochemical relapse with oligo-recurrent disease on follow-up imaging. Conclusion: The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy.

Gastrointestinal radionuclide imaging in pediatric age group.

Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the nuances of pediatric gastrointestinal imaging techniques, focusing on three specific modalities: gastric emptying scintigraphy (GES), intestinal transit scintigraphy (ITS), and gastrointestinal bleeding scintigraphy. GES involves real-time monitoring of stomach emptying using radiotracers and gamma camera technology. While challenges exist in standardizing protocols due to age-specific meal compositions, GES remains pivotal in diagnosing motility disorders, gastroesophageal reflux, and abdominal pain in children. ITS, utilizing [67Ga], provides insights into gastrointestinal motility disorders such as Hirschsprung disease. It aids in whole-gut transit evaluation, guiding surgical interventions and improving long-term clinical outcomes. Gastrointestinal bleeding scintigraphy, employing [99mTc], assists in diagnosing conditions like Meckel's diverticulum and occult bleeding, offering continuous monitoring to pinpoint the bleeding site along the entire gastrointestinal tract. SPECT-CT improves the accuracy and the standards of care. Each technique's protocol details, clinical indications, and diagnostic capabilities are thoroughly discussed, highlighting the importance of these non-invasive, functional imaging modalities in pediatric gastroenterology.

Exploring Aqueous Coordination Chemistry of Highly Lewis Acidic Metals with Emerging Isotopes for Nuclear Medicine.

ConspectusNuclear medicine harnesses radioisotopes for the diagnosis and treatment of disease. While the isotopes 99mTc and 111In have enabled the clinical diagnosis of millions of patients over the past 3 decades, more recent clinical translation of numerous 68Ga/177Lu-based radiopharmaceuticals for diagnostic imaging and therapy underscores the clinical utility of metal-based radiopharmaceuticals in mainstream cancer treatment. In addition to such established radionuclides, advancements in radioisotope production have enabled the production of radionuclides with a broad range of half-lives and emission properties of interest for nuclear medicine. Chemical means to form kinetically inert, in vivo-compatible species that can be modified with disease-targeting vectors is imperative. This presents a challenge for radiosiotopes of elements where the aqueous chemistry is still underdeveloped and poorly understood. Here, we discuss our efforts to date in exploring the aqueous, radioactive coordination chemistry of highly Lewis acidic metal ions and how our discoveries apply to the diagnosis and treatment of cancer in preclinical models of disease. The scope of this Account includes approaches to aqueous coordination of to-date understudied highly Lewis acidic metal ions with radioisotopes of emerging interest and the modulation of well-understood coordination environments of radio-coordination complexes to induce metal-catalyzed reactivity for separation and pro-drug applications.First, we discuss the development of seven-coordinate, small-cavity macrocyclic chelator platform mpatcn/picaga as an exemplary case study, which forms robust complexes with 44Sc/47Sc isotopes. Due to the high chemical hardness and pronounced Lewis acidity of the Sc3+ ion, the displacement of ternary ligand H2O by 18/natF- can be achieved to form an inert Sc-18/natF bond. Corresponding coordination complex natSc-18F is in vivo compatible and forms a theranostic tetrad with corresponding 44Sc/47Sc, 177Lu complexes all exhibiting homologous biodistribution profiles. Another exceptionally hard, highly Lewis acidic ion with underdeveloped aqueous chemistry and emerging interest in nuclear medicine is 45Ti4+. To develop de novo approaches to the mononuclear chelation of this ion under aqueous conditions, we employed a fragment-based bidentate ligand screening approach which identified two leads. The screen successfully predicted the formation of [45Ti][Ti(TREN-CAM)], a Ti-triscatechol complex that exhibits remarkable in vivo stability. Furthermore, the fragment-based screen also identified approaches that enabled solid-phase separation of Ti4+ and Sc3+ of interest in streamlining the isotope production of 45Ti and accessing new ways to separate 44Ti/44Sc for the development of a long-lived generator system. In addition to establishing the inert chelation of Ti4+ and Sc3+, we introduce controlled, metal-induced reactivity of corresponding coordination complexes on macroscopic and radiotracer scales. Metal-mediated autolytic amide bond cleavage (MMAAC) enables the temperature-dependent release of high-molar-activity, ready-to-inject radiopharmaceuticals; cleavage is selectively triggered by coordinated trivalent Lewis acid nat/68Ga3+ or Sc3+. Following the scope of reactivity and mechanistic studies, we validated MMAAC for the synthesis of high-molar-activity radiopharmaceuticals to image molecular targets with low expression and metal-mediated prodrug hydrolysis in vivo.This Account summarizes how developing the aqueous coordination chemistry and tuning the chemical reactivity of metal ions with high Lewis acidity at the macroscopic and tracer scales directly apply to the radiopharmaceutical synthesis with clinical potential.

[161Tb]Tb-PSMA-617 radioligand therapy in patients with mCRPC: preliminary dosimetry results and intra-individual head-to-head comparison to [177Lu]Lu-PSMA-617.

Rationale: Evaluation of alternative radionuclides for use in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is currently focusing on 161Tb, which may provide advantages by emitting additional Auger and conversion electrons. In this pilot study, we present preliminary dosimetry data for [161Tb]Tb-PSMA-617 RLT in a direct comparison with [177Lu]Lu-PSMA-617. Method: Six patients with metastatic castration-resistant prostate cancer (mCRPC) underwent treatment with [177Lu]Lu-PSMA-617 and subsequently - after inadequate response - with [161Tb]Tb-PSMA-617. Whole-body planar and SPECT imaging-based dosimetry of organs at risk (kidneys and salivary glands) and tumor lesions were calculated using IDAC for 177Lu and OLINDA/EXM for 161Tb. The therapeutic index (TI) of mean tumor-absorbed doses over relevant organs at risk was calculated. Results: Mean absorbed doses to organs at risk of PSMA-RLT were slightly higher for [161Tb]Tb-PSMA-617 compared to [177Lu]Lu-PSMA-617 (kidneys: 0.643 ± 0.247 vs. 0.545 ± 0.231 Gy/GBq, factor 1.18; parotid gland: 0.367 ± 0.198 vs. 0.329 ± 0.180 Gy/GBq, factor 1.10), but markedly higher regarding tumor lesions (6.10 ± 6.59 vs 2.59 ± 3.30 Gy/GBq, factor 2.40, p < 0.001). Consequently, the mean TI was higher for [161Tb]Tb-PSMA-617 compared to [177Lu]Lu-PSMA-617 for both, the kidneys (11.54 ± 9.74 vs. 5.28 ± 5.13, p = 0.002) and the parotid gland (16.77 ± 13.10 vs. 12.51 ± 18.09, p = 0.008). Conclusion: In this intra-individual head-to-head pilot study, [161Tb]Tb-PSMA-617 delivered higher tumor-absorbed doses and resulted in superior TI compared to [177Lu]Lu-PSMA-617. This preliminary data support 161Tb as a promising radionuclide for PSMA-RLT in mCRPC.

Natural Radioactivity in Raw Building Materials for Underground Parking Lots and Assessment of Radiological Health Risk for the Population.

This article reports the results of an investigation into the activity concentration of natural radionuclides in raw building materials for underground parking lots, together with the assessment of the radiation hazard for the public related to exposure to ionizing radiations. To this purpose, high-purity germanium (HPGe) γ-ray spectrometry was employed in order to quantify the average specific activity of 226Ra, 232Th, and 40K natural radioisotopes. With the aim to assess any possible radiological health risk for the population, the absorbed γ-dose rate (D), the annual effective dose equivalent outdoor (AEDEout) and indoor (AEDEin), the activity concentration index (I), and the alpha index (Iα) were also estimated, resulting in values that were lower than the maximum recommended ones for humans. Finally, the extent of the correlations existing between the observed radioactivity and radiological parameters and of these parameters with the analyzed samples was quantified through statistical analyses, including Pearson's correlation, a principal component analysis (PCA), and a hierarchical cluster analysis (HCA). As a result, three clusters of the investigated samples were recognized based on their chemical composition and mineralogical nature. Noteworthily, this paper covers a certain gap in science since its topic does not appear in literature in this form. Thus, the authors underline the importance of this work to global knowledge in the environmental research and public health fields.

Suppressive effect of Yokukansan on glutamate released from canine keratinocytes.

Background: Canine atopic dermatitis (CAD) is caused by skin barrier dysfunction due to allergen exposure. Excessive glutamate release in the skin is associated with delayed skin barrier function recovery and epidermal thickening and lichenification. Treatment with Yokukansan (YKS), a traditional Japanese medicine, reduces dermatitis severity and scratching behavior in NC/Nga mice by decreasing epidermal glutamate levels. However, the association between canine keratinocytes and glutamate and the mechanism by which YKS inhibits glutamate release from keratinocytes remains unknown. Aim: We aimed to investigate glutamate release from canine progenitor epidermal keratinocytes (CPEKs) and the inhibitory effect of YKS on this release. We also explored the underlying mechanism of YKS to enable its application in CAD treatment. Methods: Glutamate produced from CPEKs in the medium at 24 hours was measured. The measurement conditions varied in terms of cell density and YKS concentration. CPEKs were treated with a glutamate receptor antagonist (MK-801), a glutamate transporter antagonist (THA), and a glutamate dehydrogenase inhibitor (epigallocatechin gallate; EGCG), and the inhibitory effect of YKS, YKS + THA, MK-801, and EGCG on this release was determined. MK-801 and glutamate dehydrogenase inhibitor were tested alone, and THA was tested in combination with YKS. Finally, glutamine incorporated into CPEKs at 24 hours was measured using radioisotope labeling. Results: CPEKs released glutamate in a cell density-dependent manner, inhibited by YKS in a concentration-dependent manner. Moreover, YKS reduced the intracellular uptake of radioisotope-labeled glutamine in a concentration-dependent manner. No involvement of glutamate receptor antagonism or activation of glutamate transporters was found, as suggested by previous studies. In addition, EGCG could inhibit glutamate release from CPEKs. Conclusion: Our findings indicated that glutamate release from CPEKs could be effectively inhibited by YKS, suggesting the utility of YKS in maintaining skin barrier function during CAD. In addition, CPEKs are appropriate for analyzing the mechanism of YKS. However, we found that the mechanism of action of YKS differs from that reported in previous studies, suggesting that it may have had a similar effect to EGCG in this study. Further research is warranted to understand the exact mechanism and clinical efficacy in treating CAD.

Health Plan Switching and Health Care Utilization: A Randomized Clinical Trial.

Importance: While the Patient Protection and Affordable Care Act (ACA) helped make health insurance premiums more affordable with premium tax credits, ACA marketplace enrollees continue to face barriers to care. Objective: To investigate the effect of informational emails on plan switching and health care utilization. Design, Setting, and Participants: This randomized clinical trial was conducted during the 2021 special enrollment period in California's Affordable Care Act marketplace among households that reported receiving unemployment insurance and were enrolled in non-silver-tier plans. The trial targeted 42 470 households that became temporarily eligible for cost-sharing reduction (CSR) silver plans that covered 94% of medical costs (CSR silver 94 plans) as a result of the 2021 American Rescue Plan Act. Intervention: Households were randomized to either a no-email control group or to a treatment group receiving 2 informational emails encouraging households to switch to CSR plans. Main Outcomes and Measures: The primary outcome was the switch rate to a CSR silver plan by July 31, 2021. Secondary outcomes include various measures of health care utilization in the second half of 2021 (July 1, 2021, to December 31, 2021). Health care utilization was measured by rates of practitioner visits, emergency department visits, hospitalizations, and prescription fills. Results: Of the 42 470 households (head of household mean [SD], age, 41.4 [13.3] years; 51.7% male), 10 650 (25.1%) were in the control group and 31 820 (74.9%) were in the treatment group. The emails led to a statistically significant 3.1-percentage point (95% CI, 2.6-3.6 percentage points) increase in CSR silver 94 enrollment (a 74.8% relative increase) by July 31, 2021, and a 1.3-percentage point (95% CI, 0.2-2.4 percentage points) increase (a 2.3% relative increase) in practitioner visits by December 31, 2021. The emails had no detectable effect on prescription fills, emergency department visits, or hospitalizations. Conclusions and Relevance: The results of this randomized clinical trial provide experimental evidence that, with access to more affordable health care, individuals are more likely to visit practitioners. Trial Registration: ClinicalTrials.gov Identifier: NCT05891418.

Occupational skin dose from radionuclide contamination: one country's approach at standardising skin dose estimates using Varskin.

The manipulation of unsealed radiopharmaceuticals by healthcare workers can cause accidental personal contamination leading to occupational radiation skin dose. The UK Ionising Radiations Regulations 2017 require that potential skin doses arising from reasonably foreseeable accident scenarios are included in risk assessments. Workers must be designated as classified if these dose estimates exceed 150 mSv equivalent dose averaged over 1 cm2. Updates from the UK Health and Safety Executive recently prompted many in the UK to review the classification of workers in Nuclear Medicine. Skin dose from contamination cannot be measured, it must be estimated. Varskin+ is a code that is widely recommended for estimating skin dose. The subjective choices made by users when defining modelled scenarios in Varskin+ lead to significant variation in the calculated skin doses. At the time of writing there is no definitive calculation method and all calculations rely on theoretical models. NHS Health Boards in Scotland have adopted a standardised framework for performing skin dose estimates for risk assessments. The parametric sensitivity of Varskin+ inputs were examined and the available evidence was reviewed. Generic, reasonably forseeable, worst-case accident scenarios were decided upon for: direct skin contamination, glove contamination and needlestick injury. Standardised inputs and assumptions for each scenario were compiled in a protocol that has been adopted by the Scottish Health Boards. The protocol allows for differences in practice between departments, but standardises most inputs. While significant uncertainty remains in the estimated skin doses, this approach reduces variation and enables the comparison of estimated skin doses between departments. The framework facilitates continuous improvement as more evidence is gathered to refine the standardised assumptions. Task by task skin dose estimates were made for workers in Nuclear Medicine in Scotland and many workers were designated classified as a result.

Low-dose targeted radionuclide therapy synergizes with CAR T cells and enhances tumor response.

Ionizing radiation has garnered considerable attention as a combination partner for immunotherapy due to its potential immunostimulatory effects. In contrast to the more commonly used external beam radiation, we explored the feasibility of combining chimeric antigen receptor (CAR) T cell therapy with targeted radionuclide therapy (TRT), which is achieved by delivering ß-emitting 177Lu-DOTATATE to tumor via tumor-infiltrating CAR T cells that express somatostatin receptor 2 (SSTR2). We hypothesized that the delivery of radiation to tumors could synergize with CAR T therapy, resulting in enhanced antitumor immunity and tumor response. To determine the optimal dosage and timing of 177Lu-DOTATATE treatment, we measured CAR T cell infiltration and expansion in tumors longitudinally through positron emission tomography (PET) using a SSTR2-specific positron-emitting radiotracer,18F-NOTA-Octreotide. In animals receiving CAR T cells and a low-dose (2.5 Gy) of TRT following the administration of 177Lu-DOTATATE, we observed a rapid regression of large subcutaneous tumors, which coincided with a dramatic increase in serum proinflammatory cytokines. Tumor burden was also reduced when a higher radiation dose (6 Gy) was delivered to the tumor. However, this higher dose led to cell death in both the tumor and CAR T cells. Our study suggests that there may exist an optimum range of TRT dosage that can enhance T cell activity and sensitize tumor cells to T cell killing, which may result in more durable tumor control compared to a higher radiation dose.

Study on induced radioactivity and individual dose evaluation in Gantry room for Varian ProBeam Proton Therapy System.

Proton therapy has emerged as an advantageous modality for tumor radiotherapy due to its favorable physical and biological properties. However, this therapy generates induced radioactivity through nuclear reactions between the primary beam, secondary particles, and surrounding materials. This study focuses on systematically investigating the induced radioactivity in the gantry room during pencil beam scanning, utilizing both experimental measurements and Monte Carlo simulations. Results indicate that patients are the primary source of induced radioactivity, predominantly producing radionuclides such as 11C, 13N, and 15O. Long-term irradiation primarily generates radionuclides like 22Na, 24Na, and 54Mn etc. Additionally, this study estimates the individual doses received by medical workers in the gantry room, the irradiation dose for patient escorts, and the additional dose to patients from residual radiation. Finally, the study offers recommendations to minimize unnecessary irradiation doses to medical workers, patient escorts, and patients.

"Off-Label Use" of the Siderophore Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV).

The development of inert, biocompatible chelation methods is required to harness the emerging positron emitting radionuclide 45Ti for radiopharmaceutical applications. Herein, we evaluate the Ti(IV)-coordination chemistry of four catechol-based, hexacoordinate chelators using synthetic, structural, computational, and radiochemical approaches. The siderophore enterobactin (Ent) and its synthetic mimic TREN-CAM readily form mononuclear Ti(IV) species in aqueous solution at neutral pH. Radiolabeling studies reveal that Ent and TREN-CAM form mononuclear complexes with the short-lived, positron-emitting radionuclide 45Ti(IV), and do not transchelate to plasma proteins in vitro and exhibit rapid renal clearance in naïve mice. These features guide efforts to target the 45Ti isotope to prostate cancer tissue through the design, synthesis, and evaluation of Ent-DUPA, a small molecule conjugate composed of a prostate specific membrane antigen (PSMA) targeting peptide and a monofunctionalized Ent scaffold. The [45Ti][Ti(Ent-DUPA)]2- complex forms readily at room temperature. In a tumor xenograft model in mice, selective tumor tissue accumulation (8±5 %, n=5), and low off-target uptake in other organs is observed. Overall, this work demonstrates targeted imaging with 45Ti(IV), provides a foundation for advancing the application of 45Ti in nuclear medicine, and reveals that Ent can be repurposed as a 45Ti-complexing cargo for targeted nuclear imaging applications.

Extravasation After [ 177 Lu]Lu-HA-DOTATATE Therapy.

ABSTRACT: Extravasation of the radiopharmaceutical during peptide receptor radionuclide therapy infusion is an unwanted infrequently reported event. We present the case of a 74-year old woman with a neuroendocrine tumor who was referred for peptide receptor radionuclide therapy. During intravenous infusion of 7.4 GBq [ 177 Lu]Lu-HA-DOTATATE in the upper right arm, extravasation of the radiopharmaceutical occurred through a displaced intravenous catheter. Planar scintigraphy showed pooling of radioactivity in the right upper arm. After 24 hours, the swelling in the arm was decreased; however, erythema was increased. One week later, symptoms had disappeared, and the patient did not experience any complications during follow-up of 11 months.

177 Lu-FAP-2286 Therapy in a Metastatic Bone Malignant Solitary Fibrous Tumor.

ABSTRACT: A 57-year-old woman with a metastatic bone malignant solitary fibrous tumor received 177 Lu-FAP-2286 therapy. After 1 treatment cycle, 68 Ga-FAP-2286 PET/CT revealed remission of the lesions. Moreover, the patient did not report any adverse effects.