LightPRA: A Lightweight Temporal Convolutional Network for Automatic Physical Rehabilitation Exercise Assessment.

Research evidence shows that physical rehabilitation exercises prescribed by medical experts can assist in restoring physical function, improving life quality, and promoting independence for physically disabled individuals. In response to the absence of immediate expert feedback on performed actions, developing a Human Action Evaluation (HAE) system emerges as a valuable automated solution, addressing the need for accurate assessment of exercises and guidance during physical rehabilitation. Previous HAE systems developed for the rehabilitation exercises have focused on developing models that utilize skeleton data as input to compute a quality score for each action performed by the patient. However, existing studies have focused on improving scoring performance while often overlooking computational efficiency. In this research, we propose LightPRA (Light Physical Rehabilitation Assessment) system, an innovative architectural solution based on a Temporal Convolutional Network (TCN), which harnesses the capabilities of dilated causal Convolutional Neural Networks (CNNs). This approach efficiently captures complex temporal features and characteristics of the skeleton data with lower computational complexity, making it suitable for real-time feedback provided on resource-constrained devices such as Internet of Things (IoT) devices and Edge computing frameworks. Through empirical analysis performed on the University of Idaho-Physical Rehabilitation Movement Data (UI-PRMD) and KInematic assessment of MOvement for remote monitoring of physical REhabilitation (KIMORE) datasets, our proposed LightPRA model demonstrates superior performance over several state-of-the-art approaches such as Spatial-Temporal Graph Convolutional Network (STGCN) and Long Short-Term Memory (LSTM)-based models in scoring human activity performance, while exhibiting lower computational cost and complexity.

Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Don't chase the adenoma: A probabilistic approach to imaging before parathyroidectomy.

BACKGROUND: Preoperative imaging before parathyroidectomy can localize adenomas and reduce unnecessary bilateral neck explorations. We hypothesized that (1) the utility of preoperative imaging varies substantially depending on the preoperative probability of having adenoma(s) and (2) that a selective imaging approach based on this probability could avoid unnecessary patient costs and radiation. METHODS: We analyzed 3,577 patients who underwent parathyroidectomy for primary hyperparathyroidism from 2001 to 2022. The predicted probability of patients having single or double adenoma versus hyperplasia was estimated using logistic regression. We then estimated the relationship between the predicted probability of single/double adenoma and the likelihood that sestamibi or 4-dimensional computed tomography was helpful for operative planning. Current Medicare costs and published data on radiation dosing were used to calculate costs and radiation exposure from non-helpful imaging. RESULTS: The mean age was 62 ± 13 years; 78% were women. Adenomas were associated with higher mean calcium (11.2 ± 0.74 mg/dL) and parathyroid hormone levels (140.6 ± 94 pg/mL) than hyperplasia (9.8 ± 0.52 mg/dL and 81.4 ± 66 pg/mL). The probability that imaging helped with operative planning increased from 12% to 65%, as the predicted probability of adenoma increased from 30% to 90%. For every 10,000 patients, a selective approach to imaging that considered the preoperative probability of having adenomas could save patients up to $3.4 million and >239,000 millisieverts of radiation. CONCLUSION: Rather than imaging all patients with primary hyperparathyroidism, a selective strategy that considers the probability of having adenomas could reduce costs and avoid excess radiation exposure.

Combined visual and quantitative assessment of somatostatin receptor scintigraphy for staging and restaging of neuroendocrine tumors.

PURPOSE: Somatostatin receptor scintigraphy (SRS) using 111In-DTPA-DPhe1-octreotide (pentetreotide) has become an integral part of neuroendocrine neoplasm management. The lack of precise quantification is a disadvantage of SRS. This study aimed to adapt the standardized uptake value (SUV) to SRS, establish the SUV range for physiological uptake in the liver, kidney, and spleen, and elucidate the utility of combined visual and quantitative SRS assessment for staging and restaging of neuroendocrine tumors (NETs). MATERIALS AND METHODS: This study included 21 patients with NETs who underwent 111In-pentetreotide SRS. The SUV of physiological and pathological uptake was calculated using bone single-photon emission computed tomography (SPECT) quantitative analysis software (GI-BONE). For visual analysis, the primary and metastatic lesions were scored visually on planar and SPECT images using a five-point scale. We assessed the relationships between the SUVs of the liver, kidney, and spleen in the dual phase, and among quantitative indices, visual score, and pathological lesions classification. RESULTS: Sixty-three NEN lesions were evaluated. The mean ± standard deviation maximum SUVs (SUVmax) were liver: 4 h, 2.6 ± 1.0; 24 h, 2.2 ± 1.0; kidney: 4 h, 8.9 ± 1.8; 24 h, 7.0 ± 2.0; and spleen; 4 h, 11.3 ± 4.5; 24 h, 11.5 ± 7.6. Higher SUVmax was significantly associated with higher visual scores on dual-phase SPECT (4 h, p < 0.001; 24 h, p < 0.001) (4 h: scores 3 and 4, p < 0.05; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01; 24 h: scores 3 and 4, p = 0.0748; scores 3 and 5: p < 0.01; scores 4 and 5: p < 0.01). CONCLUSION: We adapted the SUV to SRS and established the range of SUV for physiological uptake in the liver, kidney, and spleen. Combined visual and quantitative assessment is useful for imaging individual lesions in greater detail, and may serve as a new tumor marker of SRS for staging and restaging of NETs.

Diagnostic approach with Z-score mapping to reduce artifacts caused by cerebral atrophy in regional CBF assessment of mild cognitive impairment (MCI) and Alzheimer's disease by [99mTc]-ECD and SPECT.

PURPOSE: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy. MATERIALS AND METHODS: [99mTc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically. RESULTS: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%. CONCLUSION: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies.

Functional and 123I-MIBG scintigraphy assessment of cardiac adrenergic dysfunction in diabetes.

OBJECTIVES: To assess the agreement between clinical cardiovascular adrenergic function and cardiac adrenergic innervation in type 2 diabetes patients (T2D). METHODS: Thirty-three patients with T2D were investigated bimodally through (1) a standardized clinical cardiovascular adrenergic assessment, evaluating adequacy of blood pressure responses to the Valsalva maneuver and (2) 123I-meta-iodobenzylguanidine (MIBG) scintigraphy assessing myocardial adrenergic innervation measured as early and delayed heart heart/mediastinum (H/M) ratio, and washout rate (WR). RESULTS: T2D patients had significantly lower early and delayed H/M-ratios, and lower WR, compared to laboratory specific reference values. Thirteen patients had an abnormal adrenergic composite autonomic severity score (CASS > 0). Patients with abnormal CASS scores had significantly higher early H/M ratios (1.76 [1.66-1.88] vs. 1.57 [1.49-1.63], p < 0.001), higher delayed H/M ratios (1.64 [1.51:1.73] vs. 1.51 [1.40:1.61] (p = 0.02)), and lower WR (-0.13(0.10) vs -0.05(0.07), p = 0.01). Lower Total Recovery and shorter Pressure Recovery Time responses from the Valsalva maneuver was significantly correlated to lower H/M early (r = 0.55, p = 0.001 and r = 0.5, p = 0.003, respectively) and lower WR for Total Recovery (r = -0.44, p = 0.01). CONCLUSION: The present study found impairment of sympathetic innervation in T2D patients based on parameters derived from MIBG cardiac scintigraphy (low early H/M, delayed H/M, and WR). These results confirm prior studies. We found a mechanistically inverted relationship with favourable adrenergic cardiovascular responses being significantly associated unfavourable MIBG indices for H/M early and delayed. This paradoxical relationship needs to be further explored but could indicate adrenergic hypersensitivity in cardiac sympathetic denervated T2D patients.

Misleading FDG Uptake in Oncology Assessment: Beyond COVID-19 Vaccination-The Role of Pneumococcal Vaccination.

ABSTRACT: Here, we report the case of a 35-year-old woman who performed PET/CT 18F-FDG as an initial workup for HER2+ right breast invasive ductal carcinoma. Examination revealed multifocal breast involvement with homolateral lymph node involvement. Contralateral axillary adenopathy and diffuse splenic and osteomedullary hypermetabolism were also observed, suggesting associated lymphoma in the absence of a recent COVID-19 vaccination. Cytopuncture was discussed and finally postponed after the patient was found to have recently received a pneumococcal vaccination.

Deep transformer-based personalized dosimetry from SPECT/CT images: a hybrid approach for [177Lu]Lu-DOTATATE radiopharmaceutical therapy.

PURPOSE: Accurate dosimetry is critical for ensuring the safety and efficacy of radiopharmaceutical therapies. In current clinical dosimetry practice, MIRD formalisms are widely employed. However, with the rapid advancement of deep learning (DL) algorithms, there has been an increasing interest in leveraging the calculation speed and automation capabilities for different tasks. We aimed to develop a hybrid transformer-based deep learning (DL) model that incorporates a multiple voxel S-value (MSV) approach for voxel-level dosimetry in [177Lu]Lu-DOTATATE therapy. The goal was to enhance the performance of the model to achieve accuracy levels closely aligned with Monte Carlo (MC) simulations, considered as the standard of reference. We extended our analysis to include MIRD formalisms (SSV and MSV), thereby conducting a comprehensive dosimetry study. METHODS: We used a dataset consisting of 22 patients undergoing up to 4 cycles of [177Lu]Lu-DOTATATE therapy. MC simulations were used to generate reference absorbed dose maps. In addition, MIRD formalism approaches, namely, single S-value (SSV) and MSV techniques, were performed. A UNEt TRansformer (UNETR) DL architecture was trained using five-fold cross-validation to generate MC-based dose maps. Co-registered CT images were fed into the network as input, whereas the difference between MC and MSV (MC-MSV) was set as output. DL results are then integrated to MSV to revive the MC dose maps. Finally, the dose maps generated by MSV, SSV, and DL were quantitatively compared to the MC reference at both voxel level and organ level (organs at risk and lesions). RESULTS: The DL approach showed slightly better performance (voxel relative absolute error (RAE) = 5.28 ± 1.32) compared to MSV (voxel RAE = 5.54 ± 1.4) and outperformed SSV (voxel RAE = 7.8 ± 3.02). Gamma analysis pass rates were 99.0 ± 1.2%, 98.8 ± 1.3%, and 98.7 ± 1.52% for DL, MSV, and SSV approaches, respectively. The computational time for MC was the highest (~2 days for a single-bed SPECT study) compared to MSV, SSV, and DL, whereas the DL-based approach outperformed the other approaches in terms of time efficiency (3 s for a single-bed SPECT). Organ-wise analysis showed absolute percent errors of 1.44 ± 3.05%, 1.18 ± 2.65%, and 1.15 ± 2.5% for SSV, MSV, and DL approaches, respectively, in lesion-absorbed doses. CONCLUSION: A hybrid transformer-based deep learning model was developed for fast and accurate dose map generation, outperforming the MIRD approaches, specifically in heterogenous regions. The model achieved accuracy close to MC gold standard and has potential for clinical implementation for use on large-scale datasets.

64Cu production via the 68Zn(p,nα)64Cu nuclear reaction: An untapped, cost-effective and high energy production route.

INTRODUCTION: Copper-64 (64Cu, t1/2 = 12.7 h) is a positron emitter well suited for theranostic applications with beta-emitting 67Cu for targeted molecular imaging and radionuclide therapy. The present work aims to evaluate the radionuclidic purity and radiochemistry of 64Cu produced via the 68Zn(p,nα)64Cu nuclear reaction. Macrocyclic chelators DOTA, NOTA, TETA, and prostate-specific membrane antigen ligand PSMA I&T were radiolabeled with purified 64Cu and tested for in vitro stability. [64Cu]Cu-PSMA I&T was used to demonstrate in vivo PET imaging using 64Cu synthesized via the 68Zn(p,nα)64Cu production route and its suitability as a theranostic imaging partner alongside 67Cu therapy. METHODS: 64Cu was produced on a 24 MeV TR-24 cyclotron at a beam energy of 23.5 MeV and currents up to 70 µA using 200 mg 68Zn encapsulated within an aluminum­indium-graphite sealed solid target assembly. 64Cu semi-automated purification was performed using a NEPTIS Mosaic-LC synthesis unit employing CU, TBP, and TK201 (TrisKem) resins. Radionuclidic purity was measured by HPGe gamma spectroscopy, while ICP-OES assessed elemental purity. Radiolabeling was performed with NOTA at room temperature and DOTA, TETA, and PSMA I&T at 95 °C. 64Cu incorporation was studied by radio-TLC. 64Cu in vitro stability of [64Cu]Cu-NOTA, [64Cu]Cu-DOTA, [64Cu]Cu-TETA, and [64Cu]Cu-PSMA I&T was assessed at 37 °C from 0 to 72 h in human blood serum. Preclinical PET imaging was performed at 1, 24, and 48 h post-injection with [64Cu]Cu-PSMA I&T in LNCaP tumor-bearing mice and compared with [68Ga]Ga-PSMA I&T. RESULTS: Maximum purified activity of 4.9 GBq [64Cu]CuCl2 was obtained in 5 mL of pH 2-3 solution, with 2.9 GBq 64Cu concentrated in 0.5 mL. HPGe gamma spectroscopy of purified 64Cu detected <0.3 % co-produced 67Cu at EOB with no other radionuclidic impurities. ICP-OES elemental analysis determined <1 ppm Al, Zn, In, Fe, and Cu in the [64Cu]CuCl2 product. NOTA, DOTA, TETA, and PSMA I&T were radiolabeled with 64Cu, resulting in maximum molar activities of 164 ± 6 GBq/µmol, 155 ± 31 GBq/µmol, 266 ± 34 GBq/µmol, and 117 ± 2 GBq/µmol, respectively. PET imaging in PSMA-expressing LNCaP xenografts resulted in high tumor uptake (SUVmean = 1.65 ± 0.1) using [64Cu]Cu-PSMA I&T, while [68Ga]Ga-PSMA I&T yielded an SUVmean of 0.76 ± 0.14 after 60 min post-injection. CONCLUSIONS: 64Cu was purified in a small volume amenable for radiolabeling, with yields suitable for preclinical and clinical application. The 64Cu production and purification process and the favourable PET imaging properties confirm the 68Zn(p,nα)64Cu nuclear reaction as a viable 64Cu production route for facilities with access to a higher energy proton cyclotron, compared to using expensive 64Ni target material and the 64Ni(p,n)64Cu nuclear reaction. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Our 64Cu production technique provides an alternative production route with the potential to improve 64Cu availability for preclinical and clinical studies alongside 67Cu therapy.

Assessment of water enema PET/CT: an effective imaging technique for the diagnosis of incidental colorectal 18F-FDG uptake.

BACKGROUND: To validate the feasibility of water enema PET/CT (WE-PET/CT) in incidental colorectal 18F-FDG uptake and improve the accuracy of diagnosing colorectal neoplastic lesions. METHODS: We retrospectively analysed the electronic records of 338 patients undergoing common PET/CT and WE-PET/CT at our hospital. PET/CT results were correlated with colonoscopy pathology and follow-up results. The ROC contrast curve was plotted to evaluate the accuracy of SUVmax on common PET/CT and WE-PET/CT for detecting neoplastic lesions. SUVmax and the median retention indexes (RIs) of cancerous, precancerous, and benign lesions and physiologic uptake were compared. RESULTS: The sensitivity, specificity and accuracy of diagnosing neoplastic lesions with common PET/CT were 84.0%, 78.3% and 80.2%, respectively. The corresponding results with WE-PET/CT were 95.8%, 96.5% and 96.2%. The AUC of SUVmax on WE-PET/CT was significantly higher than that on common PET/CT (0.935 vs. 0.524, p < 0.001). The median SUVmax on WE-PET/CT was significantly higher than that on common PET/CT in cancerous and precancerous lesions, and significantly decreased in benign lesions and physiologic uptake (p < 0.001). The RI was significantly different between cancerous lesions and physiologic uptake, between precancerous lesions and physiologic uptake, between benign lesions and physiologic uptake, and between cancerous and benign lesions (p < 0.05). CONCLUSIONS: WE-PET/CT is a noninvasive, well-tolerated and effective technique for diagnosing incidental colorectal 18F-FDG uptake. It is helpful for a timely colonoscopy and can effectively avoid an unnecessary colonoscopy for incidental colorectal 18F-FDG uptake.

[90Y]Yttria Alumino Silicate Glass Microspheres: A Biosimilar Formulation to "TheraSphere" for Cost-Effective Treatment of Liver Cancer.

Background: Selective internal radiation therapy (SIRT) using a suitable ß--emitting radionuclide is a promising treatment modality for unresectable liver carcinoma. Yttrium-90 (90Y) [T1/2 = 64.2 h, Eß(max) = 2.28 MeV, no detectable γ-photon] is the most preferred radioisotope for SIRT owing to its favorable decay characteristics. Objective: The present study describes indigenous development and evaluation of intrinsically radiolabeled [90Y]yttria alumino silicate ([90Y]YAS) glass microsphere, a formulation biosimilar to "TheraSphere" (commercially available, U.S. FDA-approved formulation), for SIRT of unresectable liver carcinoma in human patients. Methods: YAS glass microspheres of composition 40Y2O3-20Al2O3-40SiO2 (w/w) and diameter ranging between 20 and 36 µm were synthesized with almost 100% conversion efficiency and >99% sphericity. Intrinsically labeled [90Y]YAS glass microspheres were produced by thermal neutron irradiation of cold YAS glass microspheres in a research reactor. Subsequent to in vitro evaluations and in vivo studies in healthy Wistar rats, customized doses of [90Y]YAS glass microspheres were administered in human patients. Results: [90Y]YAS glass microspheres were produced with 137.7 ± 8.6 MBq/mg YAS glass (∼6800 Bq per microsphere) specific activity and 99.94% ± 0.02% radionuclidic purity at the end of irradiation. The formulation exhibited excellent in vitro stability in human serum and showed >97% retention in the liver up to 7 d post-administration when biodistribution studies were carried out in healthy Wistar rats. Yttrium-90 positron emission tomography scans recorded at different time points post-administration of customized dose of [90Y]YAS glass microspheres in human patients showed near-quantitative retention of the formulation in the injected lobe. Conclusions: The study confirmed the suitability of indigenously prepared [90Y]YAS glass microspheres for clinical use in the treatment of unresectable hepatocellular carcinoma.

Long-term assessment of clinical parameters and positron emission tomography parameters in predicting recurrence in uterine cervical cancer patients receiving definitive chemoradiotherapy.

OBJECTIVE: The objective of this study was to assess the prognostic value of clinical factors and metabolic parameters measured using fluorodeoxyglucose PET (FDG-PET/CT) in predicting disease recurrence, as well as distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and overall survival (OS) in patients with uterine cervical cancer who received definitive chemoradiotherapy. METHODS: The clinical data and FDG-PET parameters, including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of 194 patients with biopsy-confirmed squamous cell carcinoma of cervical cancer were retrospectively analyzed. Univariate and multivariate analyses were used to ascertain prognostic factors associated with DMFS, LRFS, and OS. RESULTS: With a median follow-up of 12.5 years, 96 patients (49.5%) presented with disease recurrence, at a median of 9.9 months after chemoradiotherapy. Patients who experienced recurrence had significantly higher values for all FDG-PET parameters compared to patients who did not. In multivariate regression analysis, lymph node metastasis, MTV, and SUV mean were significantly correlated with distant metastasis, while local recurrence was only predicted by SUV max . Lymph node metastasis, high MTV, SUV mean , and TLG predicted shorter DMFS, while only the primary tumor SUV max predicted LRFS. Age, regional nodal metastasis, and higher MTV independently predicted shorter OS in multivariate analysis. CONCLUSION: We found that metabolic parameters derived from FDG-PET/CT could serve as surrogates for disease recurrence in patients with cervical cancer who were treated with definitive chemoradiotherapy. Patients at high risk of distant metastasis could be defined using SUV mean and MTV, and for local recurrence, by using SUV max .

PET/Computed Tomography Transformation of Oncology: Immunotherapy Assessment.

Immunotherapy approaches have changed the treatment landscape in a variety of malignancies with a high anti-tumor response. Immunotherapy may be associated with novel response and progression patterns that pose a substantial challenge to the conventional criteria for assessing treatment response, including response evaluation criteria in solid tumors (RECIST) 1.1. In addition to the morphologic details provided by computed tomography (CT) and MRI, hybrid molecular imaging emerges as a comprehensive imaging modality with the capacity to interrogate pathophysiological mechanisms like glucose metabolism. This review highlights the current status of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in prognostication, response monitoring, and identifying immune-related adverse events. Furthermore, it investigates the potential role of novel immuno-PET tracers that could complement the utilization of 18F-FDG PET/CT by imaging the specific pathways involved in immunotherapeutic strategies.

Comparative assessment of radiation therapy-induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy.

PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.

FDG-PET/CT for investigation of pyrexia of unknown origin: a cost of illness analysis.

BACKGROUND: Our study aims to explore the current utilisation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the diagnostic pathway of pyrexia of unknown origin (PUO) and associated cost of illness in a large tertiary teaching hospital in Australia. METHOD: 1257 febrile patients between June 2016 and September 2022 were retrospectively reviewed. There were 57 patients who met the inclusion criteria of "classical PUO", of which FDG-PET/CT was performed in 31 inpatients, 15 outpatients and 11 inpatients did not have an FDG-PET/CT scan. The patient demographics, clinical characteristics and inpatient cost were analysed, together with the diagnostic performance of FDG-PET/CT and impact on clinical management. RESULT: The mean age, length of stay and total cost of admission were higher for inpatients who received FDG-PET/CT versus those who did not. The median cost per patient-bed-day did not differ between the two groups. Inpatients who received earlier FDG-PET/CTs (≤ 7 days from admission) had shorter length of stays and lower total cost compared to those who received a later scan. A negative FDG-PET/CT scan, demonstrating no serious or life-threatening abnormalities resulted in subsequent discharge from hospital or outpatient clinic in 7/10 (70%) patients. There were 11/40 (28%) scans where ancillary abnormalities were identified, requiring further evaluation. CONCLUSION: FDG-PET/CT showed high diagnostic accuracy and significant impact on patient management in patients with PUO. FDG-PET/CT performed earlier in admission for PUO was associated with shorter length of stay and lower total cost.

The role of conventional and novel PET radiotracers in assessment of myeloma bone disease.

Over 80 % of patients with multiple myeloma (MM) experience osteolytic bone lesions, primarily due to an imbalanced interaction between osteoclasts and osteoblasts. This imbalance can lead to several adverse outcomes such as pain, fractures, limited mobility, and neurological impairments. Myeloma bone disease (MBD) raises the expense of management in addition to being a major source of disability and morbidity in myeloma patients. Whole-body x-ray radiography was the gold standard imaging modality for detecting lytic lesions. Osteolytic lesions are difficult to identify at an earlier stage on X-ray since the lesions do not manifest themselves on conventional radiographs until at least 30 % to 50 % of the bone mass has been destroyed. Hence, early diagnosis of osteolytic lesions necessitates the utilization of more complex and advanced imaging modalities, such as PET. One of the PET radiotracers that has been frequently investigated in MM is 18F-FDG, which has demonstrated a high level of sensitivity and specificity in detecting myeloma lesions. However, 18F-FDG PET/CT has several restrictions, and therefore the novel PET tracers that can overcome the limitations of 18F-FDG PET/CT should be further examined in assessment of MBD. The objective of this review article is to thoroughly examine the significance of both conventional and novel PET radiotracers in the assessment of MBD. The intention is to present the information in a manner that would be easily understood by healthcare professionals from diverse backgrounds, while minimizing the use of complex nuclear medicine terminology.

Quantitative and Qualitative Assessment of Urinary Activity of 18F-Flotufolastat-PET/CT in Patients with Prostate Cancer: a Post Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies.

PURPOSE: To evaluate the impact of urinary activity on interpretation of 18F-flotufolastat (18F-rhPSMA-7.3) PET/CT, we conducted a post hoc qualitative and quantitative analysis of scans acquired in two phase 3 studies of 18F-flotufolastat. PROCEDURES: Newly diagnosed or recurrent prostate cancer patients enrolled in LIGHTHOUSE (NCT04186819) or SPOTLIGHT (NCT04186845), respectively, underwent PET/CT 50-70 min after intravenous administration of 296 MBq 18F-flotufolastat. For the present analysis, 718 18F-flotufolastat scans (352 from LIGHTHOUSE and 366 from SPOTLIGHT) were re-evaluated by three board-certified nuclear medicine physicians. Reader 1 performed a quantitative assessment (SUVmax and SUVmean) of bladder activity in a circular region-of-interest over the maximum diameter of bladder activity in the transverse plane. All three readers qualitatively assessed the impact of any urinary activity in the bladder on image interpretation using a three-point scale (0 = no/minimal visible urinary activity, 1 = urinary activity visible but distinction between urine and disease possible and 2 = assessment inhibited by urinary activity) and the presence/absence of ureteric activity and halo artifacts. RESULTS: In total, 712/718 scans were evaluable. Reasons for exclusion were cystectomy, renal failure, or urinary catheter in situ (n = 2 each). The median bladder SUVmax and SUVmean were 17.1 and 12.5, respectively. By majority read, 682/712 (96%) patients had either no urinary activity (score = 0) or visible activity that could be distinguished from disease uptake (score = 1). In the minority of patients (24, 3.4%) where urinary activity did impact assessment (score = 2), the median bladder SUVmean was higher (20.5) than those scored 0 (3.8) or 1 (14.0). Ureteric activity was absent in 401 (56%) patients. Halo artifacts were observed in only two (0.3%) patients (majority read). CONCLUSIONS: 18F-Flotufolastat urinary activity did not influence disease assessment for the majority of patients. While this study was not designed as a head-to-head comparison, the median bladder SUVs are lower than previously reported values for other renally cleared PSMA-PET radiopharmaceuticals.

Low cost, high temporal resolution optical fiber-based γ-photon sensor for real-time pre-clinical evaluation of cancer-targeting radiopharmaceuticals.

Cancer radiopharmaceutical therapies (RPTs) have demonstrated great promise in the treatment of neuroendocrine and prostate cancer, giving hope to late-stage metastatic cancer patients with currently very few treatment options. These therapies have sparked a large amount of interest in pre-clinical research due to their ability to target metastatic disease, with many research efforts focused towards developing and evaluating targeted RPTs for different cancer types in in vivo models. Here we describe a method for monitoring real-time in vivo binding kinetics for the pre-clinical evaluation of cancer RPTs. Recognizing the significant heterogeneity in biodistribution of RPTs among even genetically identical animal models, this approach offers long-term monitoring of the same in vivo organism without euthanasia in contrast to ex vivo tissue dosimetry, while providing high temporal resolution with a low-cost, easily assembled platform, that is not present in small-animal SPECT/CTs. The method utilizes the developed optical fiber-based γ-photon biosensor, characterized to have a wide linear dynamic range with Lutetium-177 (177Lu) activity (0.5-500 µCi/mL), a common radioisotope used in cancer RPT. The probe's ability to track in vivo uptake relative to SPECT/CT and ex vivo dosimetry techniques was verified by administering 177Lu-PSMA-617 to mouse models bearing human prostate cancer tumors (PC3-PIP, PC3-flu). With this method for monitoring RPT uptake, it is possible to evaluate changes in tissue uptake at temporal resolutions <1 min to determine RPT biodistribution in pre-clinical models and better understand dose relationships with tumor ablation, toxicity, and recurrence when attempting to move therapies towards clinical trial validation.