Pyrite-stimulated bio-reductive immobilization of perrhenate: Insights from integrated biotic and abiotic perspectives.

Microbes possessing electron transfer capabilities hold great promise for remediating subsurface contaminated by redox-active radionuclides such as technetium-99 (99TcO4-) through bio-transformation of soluble contaminants into their sparingly soluble forms. However, the practical application of this concept has been impeded due to the low electron transfer efficiency and long-term product stability under various biogeochemical conditions. Herein, we proposed and tested a pyrite-stimulated bio-immobilization strategy for immobilizing ReO4- (a nonradioactive analogue of 99TcO4-) using sulfate-reducing bacteria (SRB), with a focus on pure-cultured Desulfovibrio vulgaris. Pyrite acted as an effective stimulant for the bio-transformation of ReO4-, boosting the removal rate of ReO4- (50 mg/L) in a solution from 2.8 % (without pyrite) to 100 %. Moreover, the immobilized products showed almost no signs of remobilization during 168 days of monitoring. Dual lines of evidence were presented to elucidate the underlying mechanisms for the pyrite-enhanced bio-activity. Transcriptomic analysis revealed a global upregulation of genes associated with electron conductive cytochromes c network, extracellular tryptophan, and intracellular electron transfer units, leading to enhanced ReO4- bio-reduction. Spectroscopic analysis confirmed the long-term stability of the bio-immobilized products, wherein ReO4- is reduced to stable Re(IV) oxides and Re(IV) sulfides. This work provides a novel green strategy for remediation of radionuclides- or heavy metals-contaminated sites.

Comparative post-therapeutic dosimetry between 2D planar-based and hybrid-based methods for personalized Lu-177 treatment.

PURPOSE: This study aims to compare the calculated absorbed dose in target organs and tumors obtained using the different imaging protocols and the calculation methodologies implemented by HERMES HybridViewer dosimetry software for 177Lu-PSMA I&T and 177Lu-DOTATATE therapy. METHODS: Multiple time-point whole-body planar images and one SPECT/CT image were acquired from 18 patients including 177Lu-PSMA I&T (13 patients) and 177Lu-DOTATATE treatment (5 patients) after administration of 3.80-8.58 GBq injected activity. The regions of interest were drawn in the whole body, kidneys, liver, urinary bladder, salivary glands, and tumors to determine the time-integrated activity (TIA) in source organs. Absorbed doses in target organs were calculated according to the Medical Internal Radiation Dose (MIRD) scheme using the HERMES HybridViewer dosimetry integrated with OLINDA/EXM V.2.1 that utilizes the non-uniform rational B-splines (NURBS) for computational digital phantom. RESULTS: The planar-based dosimetry showed a higher dose per injected activity compared to the hybrid-based dosimetry, primarily due to organ overlap. The highest difference in absorbed dose between the imaging scenarios was observed in the spleen with a variation of up to 51.6%, while the difference for other target organs and tumors was less than 40%. CONCLUSION: The dosimetry calculation derived from the 2D planar-based method consistently demonstrates a significantly higher absorbed dose in organs and tumors compared with the hybrid-based method. However, the hybrid method outperforms the planar method in terms of tumor visualization and overlap-free organ delineation.

Towards effective CAIX-targeted radionuclide and checkpoint inhibition combination therapy for advanced clear cell renal cell carcinoma.

Background: Immune checkpoint inhibitors (ICI) are routinely used in advanced clear cell renal cell carcinoma (ccRCC). However, a substantial group of patients does not respond to ICI therapy. Radiation is a promising approach to increase ICI response rates since it can generate anti-tumor immunity. Targeted radionuclide therapy (TRT) is a systemic radiation treatment, ideally suited for precision irradiation of metastasized cancer. Therefore, the aim of this study is to explore the potential of combined TRT, targeting carbonic anhydrase IX (CAIX) which is overexpressed in ccRCC, using [177Lu]Lu-DOTA-hG250, and ICI for the treatment of ccRCC. Methods: In this study, we evaluated the therapeutic and immunological action of [177Lu]Lu-DOTA-hG250 combined with aPD-1/a-CTLA-4 ICI. First, the biodistribution of [177Lu]Lu-DOTA-hG250 was investigated in BALB/cAnNRj mice bearing Renca-CAIX or CT26-CAIX tumors. Renca-CAIX and CT26-CAIX tumors are characterized by poor versus extensive T-cell infiltration and homogeneous versus heterogeneous PD-L1 expression, respectively. Tumor-absorbed radiation doses were estimated through dosimetry. Subsequently, [177Lu]Lu-DOTA-hG250 TRT efficacy with and without ICI was evaluated by monitoring tumor growth and survival. Therapy-induced changes in the tumor microenvironment were studied by collection of tumor tissue before and 5 or 8 days after treatment and analyzed by immunohistochemistry, flow cytometry, and RNA profiling. Results: Biodistribution studies showed high tumor uptake of [177Lu]Lu-DOTA-hG250 in both tumor models. Dose escalation therapy studies in Renca-CAIX tumor-bearing mice demonstrated dose-dependent anti-tumor efficacy of [177Lu]Lu-DOTA-hG250 and remarkable therapeutic synergy including complete remissions when a presumed subtherapeutic TRT dose (4 MBq, which had no significant efficacy as monotherapy) was combined with aPD-1+aCTLA-4. Similar results were obtained in the CT26-CAIX model for 4 MBq [177Lu]Lu-DOTA-hG250 + a-PD1. Ex vivo analyses of treated tumors revealed DNA damage, T-cell infiltration, and modulated immune signaling pathways in the TME after combination treatment. Conclusions: Subtherapeutic [177Lu]Lu-DOTA-hG250 combined with ICI showed superior therapeutic outcome and significantly altered the TME. Our results underline the importance of investigating this combination treatment for patients with advanced ccRCC in a clinical setting. Further investigations should focus on how the combination therapy should be optimally applied in the future.

Intra-arterial PRRT with Lu-177 DOTATATE in Liver-dominant Metastatic Neuroendocrine Tumors: Early Assessment of Efficacy and Toxicity.

Purpose: We proposed to administer Lu-177-DOTATATE in intra-arterial (IA) mode for higher first-pass localization to somatostatin receptors, higher residence time in liver metastases, and more radiation to tumor. This study aimed at assessing early hematological, renal and hepatotoxicity; and objective response to IA peptide receptor radionuclide therapy (PRRT). Materials and Methods: Fourteen patients (4 females and 10 males) were prospectively assessed. 5/14 patients underwent 2 cycles, whereas 3/14 underwent 3 cycles, and 6/14 received 1 cycle of IA PRRT. 200 mCi of Lu-177-DOTATATE was administered in 15-20 min by IA route under angiographic guidance. Patients were asked to follow-up at 4 and 8 weeks with hematological, liver, and renal functional parameters, and Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) after 8 weeks. Response was assessed using RECIST 1.1 and EORTC PET criteria. Results: Safety: 2/14 patients had high total and direct bilirubin, which reverted to normal after IA PRRT. Three patients had low albumin, which improved after 1 cycle. Nine patients showed no worsening of liver function. Two patients showed Grade 1 hematotoxicity which reverted to normal. Five patients showed high creatinine, but preserved glomerular filtration rate and EC clearance. On follow-up at 8 weeks, serum creatinine reverted to normal. Efficacy: In five patients who underwent 2 cycles of IA PRRT, 3 showed partial response (PR) on RECIST 1.1 and partial metabolic response (PMR) on EORTC criteria, whereas 2 showed stable disease (SD). In patients who underwent 3 cycles, 1 showed SD, whereas other patient showed PMR on DOTANOC PET/CT, with PR in size. Among the remaining seven patients, 5 showed PMR, whereas the other 2 showed SD. Thus 9/14 patients showed PR, whereas 5 showed SD on metabolic and size criteria. Conclusions: IA PRRT is a safe and efficacious approach for the treatment of liver dominant metastatic neuroendocrine tumors.

An electrochemical generator for the continual supply of 213Bi from 225Ac for use in targeted alpha therapy applications.

Bismuth-213 is a radionuclide of interest for targeted alpha therapy and is supplied via a radiochemical generator system through the decay of 225Ac. Radionuclide generators employ longer lived "parent" radionuclides to routinely supply shorter-lived "daughter" radionuclides. The traditional 225Ac/213Bi radiochemical generator relies on an organic cation exchange resin where 225Ac binds to the resin and 213Bi is routinely eluted. These resins degrade when they absorb large doses of ionizing radiation (>1 × 106 Gy/mg), which has been observed when the loading activity of 225Ac exceeds 2.59*109 Bq (70 mCi). Herein we report the development of an electrochemical generator for the supply of 213Bi that has the potential to overcome this limitation. Bismuth-213 spontaneously electrodeposits onto nickel foils in 0.1 M hydrochloric acid at 70 °C. Using this method, we were able to plate an average of 73 ± 4 % of the 213Bi in solution and obtain a final 213Bi recovery of 65 ± 8 % in 0.1 M citrate pH 4.5 via reverse electrolysis using titanium as the cathode. The recovered 213Bi had an average radiochemical purity of >99.8 % and was successfully used to radiolabel DOTATATE with an average radiochemical yield of 85.1 % (not optimized).

Treatment of an Aggressive Gonadotroph Pituitary Neuroendocrine Tumor With 177Lutetium DOTATATE Radionuclide Therapy.

Aggressive pituitary neuroendocrine tumors (PitNETs) present significant morbidity, and multimodal therapies including surgery, radiotherapy, and medications are frequently required. Chemotherapy, particularly temozolomide, is often pursued for tumors that progress despite these treatments. Although peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs is approved for the treatment of well-differentiated gastrointestinal neuroendocrine tumors, its use in aggressive PitNETs is limited. We describe the case of a 65-year-old man who presented with vision changes and hypopituitarism at age 33 secondary to a nonfunctioning gonadotroph PitNET. His initial treatment included a craniotomy followed by radiation therapy. With tumor regrowth, he required transsphenoidal surgeries at age 44 and age 52. At age 56, further tumor regrowth and a positive octreotide scan prompted treatment with long-acting octreotide for 1 year. Given absent tumor response, 12 cycles (4 treatment cycles and 8 maintenance cycles) of PRRT with 177Lutetium-DOTATATE were pursued. This resulted in partial response with significant tumor shrinkage. Notably, there was no tumor regrowth 40 months after treatment discontinuation. This is only the second report on the effectiveness of PRRT in patients with aggressive gonadotroph PitNETs. We also provide an overview of PRRT for PitNETs and describe clinical outcomes previously reported in the literature.

Distribution of 137Cs specific activity in river sediments of the Barents Sea basin (Nenets Autonomous Okrug, Russian Arctic).

This article focuses on the study of the distribution of 137Cs in the bottom sediments of Arctic rivers of the Barents Sea basin (using the example of the Nenets Autonomous Okrug, Russian Arctic). This research is relevant due to the poorly studied region and the significant number of radiation-hazardous facilities in the Arctic zone of Russia, both those currently in operation and those that are "nuclear heritage sites". The study of 137Cs specific activity in bottom sediments was carried out in the period from 2020 to 2023 in the rivers Chizha, Nes, Vizhas, Oma, Pechora (river delta), as well as the rivers Kolva and Usa (first and second order tributaries, respectively, of the Pechora River). A total of 199 samples were collected. In addition to 137Cs specific activity, the samples were analysed for sediment particle size distribution, organic matter content, carbonate content and ash content. The 137Cs specific activity mainly ranged from the minimum detectable specific activity to 5.4 ± 0.8 Bq·kg-1. In the Nes River basin (Kaninskaya tundra), the 137Cs content in bottom sediments reached 36.0 ± 3.2 Bq·kg-1 (in the case of lake sediments) and 22.9 ± 3.7 Bq·kg-1 (in the case of river sediments), values that are higher than those of the North-West of Russia. Considering the large area of the study area (Kaninskaya tundra, Pechora river delta, southern part of Bolshezemelskaya tundra) and the similarity of physical and chemical parameters of the studied rivers, it is possible to assume the existence of a zone of increased radionuclide content in the Nes river basin. This may be due to the runoff from the Nes River catchment area, its hydrological features, and the accumulation of 137Cs in the small fractions of bottom sediments. The results confirm the conclusions of previous soil studies in the Nes river basin. The main sources of elevated 137Cs content are global atmospheric deposition and the Chernobyl Nuclear Power Plant accident.

Amino modified nanofibers anchored to Prussian blue nanoparticles selectively remove Cs+ from water.

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.

Characteristics of radioactive aerosols during the pre-decommission phase of the experimental shielding reactor.

The decommissioning of nuclear reactors is a global concern, in part because of the generation of radioactive aerosols that can lead to internal radiation exposure. At present, radioactive aerosols generated during nuclear decommissioning have not been actively studied, and data collected from the actual decommissioning are limited. This paper presents a study of radioactive aerosols generated during the pre-decommission phase of an experimental shielding reactor. Among all the on-site operations, cutting resulted in the highest levels of radioactivity. Plasma arc cutting, in particular, had a maximum gross α and ß radioactivity over 0.10 and 0.14 Bq/m3, respectively. Assumed AMAD (activity median aerodynamic diameter) values are employed to assess the impact of particle size on the internal exposure dose resulting from the inhalation of 137Cs aerosols based on the Human Respiratory Tract Model of International Commission on Radiological Protection. When cutting stainless steel by plasma arc, the internal exposure dose caused by 137Cs aerosols with an AMAD of 0.1 µm is estimated to be nearly four times as that of aerosols with an AMAD of 10 µm. Results show that the internal exposure dose is highly dependent on the AMAD, implying the importance of measuring size-related parameters of radioactive aerosols in the future nuclear decommissioning. This study has revealed some characteristics of radioactive aerosols released in decommissioning operations, which can serve as a valuable reference for controlling and removing aerosols during the decommissioning of nuclear facilities.

Evaluation of sarcoidosis with multiple bone lesions using both bone scintigraphy and FDG-PET/CT: A case report.

Sarcoidosis is a systemic granulomatous disease; however, the incidence of bone sarcoidosis is relatively rare. The short tubular bones of the hands and feet are most frequently affected, while the vertebrae and the pelvic bones are rarely involved. We hereby report a rare case of multiple bone sarcoidosis involving the vertebrae and pelvic bones, evaluated before and after steroid therapy using two different imaging modalities: bone scintigraphy and A 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). FDG-PET/CT is effective for detecting bone lesions; however, whole-body imaging is recommended to detect the short tubular bones of the hands and feet, which are most frequently affected.

Targeted delivery of activatable 131I-radiopharmaceutical for sustained radiotherapy with improved pharmacokinetics.

Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering legumain is overexpressed in multiple types of human cancers, a 131I-labeled radiopharmaceutical ([131I]MAAN) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) was developed by us recently for treating legumain-overexpressed tumors. However, liver enrichment limits its application. In this study, a new radiopharmaceutical [131I]IM(HE)3AAN was designed and synthesized by introducing a hydrophilic peptide sequence His-Glu-His-Glu-His-Glu ((HE)3) into [131I]MAAN to optimize the pharmacokinetics. Upon activation by legumain under a reducing environment, hydrophilic [131I]IM(HE)3AAN could react with its precursor to form heterologous dimer [131I]H-Dimer that is highly hydrophobic. Cerenkov imaging revealed that [131I]IM(HE)3AAN displayed superior tumor selectivity and longer tumor retention time as compared with [131I]MAAN, with a significant reduction in the liver uptake. After an 18-day treatment with [131I]IM(HE)3AAN, the tumor proliferation was obviously inhibited, while no obvious injury was observed in the normal organs. These findings suggest that [131I]IM(HE)3AAN could serve as a promising drug candidate for treating legumain-overexpressed tumors.

Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study.

Nonmelanoma skin cancer and its treatment represent a significant global cancer burden for health care systems and patients. [188Re]resin skin cancer therapy (Rhenium SCT) is a novel noninvasive radionuclide nonmelanoma skin cancer treatment, which can be provided in a single outpatient session. The aim of this prospective, multicenter, single-arm, international, phase IV study (EPIC-Skin) is to assess clinic- and patient-reported outcomes of Rhenium SCT as a treatment for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: Eligible patients had biopsy-proven stage I or stage II BCC or SCC lesions no more than 3 mm deep and no larger than 8 cm2 in area. Rhenium SCT resin was applied to an adhesive foil affixed to the target lesion in a single session. Interim efficacy and safety analysis were planned once 50% of target patients had recorded a 6-mo follow-up visit. Primary outcome is the proportion of lesions achieving complete response using modified RECIST. Secondary and other outcome measures include patient-reported quality of life (QoL), treatment comfort, and cosmesis. Results: A total of 182 patients was enrolled and administered Rhenium SCT (50 Gy dose to deepest point of target) to at least 1 BCC or SCC. Of 81 patients who reached the 6-mo posttreatment follow-up, it was found that 97.2% (103/106) of lesions showed complete responses and 2.8% (3/106) had partial responses. Improvements in QoL were also reported, whereas no patients reported any pain or discomfort during treatment. Adverse events were reported in 15.9% (29/182) of patients and were rated grade 1 (n = 19), grade 2 (n = 9), or grade 3 (n = 1). Conclusion: This preliminary analysis of the EPIC-Skin study indicates that Rhenium SCT is safe and effective for the treatment of BCC and SCC and is associated with significant QoL improvements. It will be particularly beneficial for lesions that are difficult to treat surgically because of size and location. It is also beneficial for patients with comorbidities or those unable to receive conventional fractionated radiotherapy.

Comparison of 177Lu-octreotate and 177Lu-octreotide for treatment in human neuroblastoma-bearing mice.

Background: Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177Lu-octreotate and 177Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177Lu-octreotate or 177Lu-octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177Lu-octreotide compared to 177Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177Lu-octreotate, respectively. 177Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8, TNSFS10, and TRADD were regulated after administration with 177Lu-octreotate. Treatment with 177Lu-octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD, and of the anti-apoptotic gene IL10 as well as the apoptosis-related gene TNF. Conclusion: 177Lu-octreotide gave somewhat better anti-tumor effects than 177Lu-octreotate. The similar effect observed in the treated groups with 177Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti-tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0.

PURPOSE: To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands. METHODS: This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). RESULTS: Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma. CONCLUSION: These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations.

Improvements of 177Lu SPECT images from sparsely acquired projections by reconstruction with deep-learning-generated synthetic projections.

BACKGROUND: For dosimetry, the demand for whole-body SPECT/CT imaging, which require long acquisition durations with dual-head Anger cameras, is increasing. Here we evaluated sparsely acquired projections and assessed whether the addition of deep-learning-generated synthetic intermediate projections (SIPs) could improve the image quality while preserving dosimetric accuracy. METHODS: This study included 16 patients treated with 177Lu-DOTATATE with SPECT/CT imaging (120 projections, 120P) at four time points. Deep neural networks (CUSIPs) were designed and trained to compile 90 SIPs from 30 acquired projections (30P). The 120P, 30P, and three different CUSIP sets (30P + 90 SIPs) were reconstructed using Monte Carlo-based OSEM reconstruction (yielding 120P_rec, 30P_rec, and CUSIP_recs). The noise levels were visually compared. Quantitative measures of normalised root mean square error, normalised mean absolute error, peak signal-to-noise ratio, and structural similarity were evaluated, and kidney and bone marrow absorbed doses were estimated for each reconstruction set. RESULTS: The use of SIPs visually improved noise levels. All quantitative measures demonstrated high similarity between CUSIP sets and 120P. Linear regression showed nearly perfect concordance of the kidney and bone marrow absorbed doses for all reconstruction sets, compared to the doses of 120P_rec (R2 ≥ 0.97). Compared to 120P_rec, the mean relative difference in kidney absorbed dose, for all reconstruction sets, was within 3%. For bone marrow absorbed doses, there was a higher dissipation in relative differences, and CUSIP_recs outperformed 30P_rec in mean relative difference (within 4% compared to 9%). Kidney and bone marrow absorbed doses for 30P_rec were statistically significantly different from those of 120_rec, as opposed to the absorbed doses of the best performing CUSIP_rec, where no statistically significant difference was found. CONCLUSION: When performing SPECT/CT reconstruction, the use of SIPs can substantially reduce acquisition durations in SPECT/CT imaging, enabling acquisition of multiple fields of view of high image quality with satisfactory dosimetric accuracy.

Therapeutic Response to PRRNT in a Rare Case of Metastatic Renal Neuroendocrine Carcinoma.

Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.

PET quantification performance of the oversize-volume-of-interest approach in the context of tumour dosimetry in radionuclide therapy planning.

OBJECTIVE: The partial-volume effect (PVE) is an important factor impairing tumour quantification in molecular imaging. The commonly used contour-volume-of-interest (contour-VOI) approach to correct for this effect employs phantom-based recovery coefficients. Applying oversize-VOIs could offer superior quantification accuracy in small lesions. The oversize-VOI approach uses a large oversize volume to determine the total tumour activity after applying a background correction. Aims of this study were to provide a procedure for the application of an oversize-VOI approach and to compare its performance to the contour-VOI approach in PET imaging. APPROACH: A sphere tumour model was simulated to determine the oversize diameter that contained 90%, 95%, and 98% of the total activity as a function of the tumour size. Experimental investigations involving phantom and clinical data were conducted on a digital PET/CT scanner. In the phantom investigation, 12 spherical tumour inserts (diameters ranging from 3.7 to 37.4 mm) containing18F-solution were used. The accuracy of the contour- and oversize-VOI approach was evaluated for different signal-to-background ratios (20 to 3). Clinically, both approaches were applied on PET/CT images acquired with18F-labelled prostate-specific membrane antigen in prostate cancer patients. MAIN RESULTS: From the tumour model, we deduced that an oversize-VOI of two PET spatial resolutions larger than the physical lesion diameter contains at least 98% of the total activity for lesions with diameters down to one PET spatial resolution, while minimizing the background contribution. Both approaches were robust against varying phantom and clinical imaging conditions. Performance of the oversize-VOI approach was favorable for lesions below 10 mm in diameter, whereas the contour-VOI approach was slightly more accurate for sizes above 10 mm. SIGNIFICANCE: The oversize-VOI approach facilitates image quantification of small tumours. It is simple and effective to correct for the PVE, and may be used in pre-therapeutic (small) tumour dosimetry.

Precision Atomistic Structures of Actinium-/Radium-/Barium-Doped Lanthanide Nanoconstructs for Radiotherapeutic Applications.

Lanthanide vanadate (LnVO4) nanoconstructs have generated considerable interest in radiotherapeutic applications as a medium for nanoscale-targeted drug delivery. For cancer treatment, LnVO4 nanoconstructs have shown promise in encapsulating and retaining radionuclides that emit alpha-particles. In this work, we examined the structure formation of LnVO4 nanoconstructs doped with actinium (Ac) and radium (Ra), both experimentally and using large-scale atomistic molecular dynamics simulations. LnVO4 nanoconstructs were synthesized via a precipitation method in aqueous media. The reaction conditions and elemental compositions were varied to control the structure, fluorescence properties, and size distribution of the LnVO4 nanoconstructs. LnVO4 nanoconstructs were characterized by X-ray diffraction, Raman spectroscopy, and fluorescence spectroscopy. Molecular dynamics simulations were performed to obtain a fundamental understanding of the structure-property relationship between radionuclides and LnVO4 nanoconstructs at the atomic length scale. Molecular dynamics simulations with well-established force field (FF) parameters show that Ra atoms tend to distribute across the nanoconstructs' surface in a broader coordination shell, while the Ac atoms are arranged inside a smaller coordination shell within the nanocluster. The Ba atoms prefer to self-assemble around the surface. These theoretical/simulation predictions of the atomistic structures and an understanding of the relationship between radionuclides and LnVO4 nanoconstructs at the atomic scale are important because they provide design principles for the future development of nanoconstructs for targeted radionuclide delivery.

Fundamentals and recent advances in the evaluation and management of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a rare primary neuroendocrine thyroid carcinoma that is distinct from other thyroid or neuroendocrine cancers. Most cases of MTC are sporadic, although MTC exhibits a high degree of heritability as part of the multiple endocrine neoplasia syndromes. REarranged during Transfection (RET) mutations are the primary oncogenic drivers and advances in molecular profiling have revealed that MTC is enriched in druggable alterations. Surgery at an early stage is the only chance for cure, but many patients present with or develop metastases. C-cell-specific calcitonin trajectory and structural doubling times are critical biomarkers to inform prognosis, extent of surgery, likelihood of residual disease, and need for additional therapy. Recent advances in the role of active surveillance, regionally directed therapies for localized disease, and systemic therapy with multi-kinase and RET-specific inhibitors for progressive/metastatic disease have significantly improved outcomes for patients with MTC.

Assessment of soil erosion in the Upper Citarum watershed for sustainability of the Saguling reservoir: unmixing model approach.

The Citarum watershed and the Saguling reservoir are vital natural resources in Indonesia, affecting the livelihood of West Java and the DKI Jakarta population. This study aimed to assess the soil erosion in the Upper Citarum watershed and identify its source. The study used the fallout radionuclide technique, geochemical tracers, and an unmixing model to measure soil erosion and the contribution of suspended sediment sources due to erosion. Soil bulk transects and surface soil were sampled using a coring tool on the Ciwidey and Cisangkuy sub-watersheds. Riverbank and suspended sediment samples were collected from tributaries and rivers. With 137Cs, 40% of the samples had values below the minimum detectable activity, and vice versa for 210Pbex, all samples are detectable. For mitigation, bare land needs to be recovered due to its erosion (25.6 t ha-1 year-1) exceeding the tolerance erosion value (17 t ha-1 year-1). Statistically, Mg and Na were the most appropriate composite tracers for suspended sediment contribution. The unmixing model predicted the sediment contributors from bare land (58%), the riverbank (32.7%), and plantation land (9.3%). Proper land conservation could reduce sediment supply by almost 14.7% and extend the reservoir's life. This is the first study to report the feasibility of the unmixing model in Indonesia.