Physiological Uptake Research Articles

Different PSMA Radiopharmaceuticals: A Comparative Study of [18F]F-PSMA-1007, [18F]F-JK-PSMA-7, and [99mTc]Tc-PSMA-I&S in the Skeletal System

Background: Numerous PSMA-based tracers are used for diagnostic prostate cancer imaging, but comprehensive comparisons between multiple ligands are lacking. This study aimed to compare physiological skeletal uptake and tracer uptake in commonly recommended PSMA reference regions across three different PSMA ligands in prostate cancer patients. Methods: A total of 281 prostate cancer patients were included. Using PET and SPECT imaging, target volumes of interest were defined via a semiautomatic method, and standardized uptake values (SUV) were calculated for the skeletal system and reference regions (liver, spleen, parotid gland, and blood pool). Results: Significant differences in SUV uptake were observed, with [18F]F-PSMA-1007 showing higher SUV values in the skeletal system. The parotid gland displayed the highest variability in uptake, while the blood pool and liver exhibited more homogeneous uptake across patients. Conclusions: While radioligands behave similarly in bone regions, there are notable differences in SUV patterns, particularly for PSMA-1007, which showed higher bone uptake. Parotid gland uptake variability suggests a reconsideration of its suitability as a reference region, while the liver, spleen, and blood pool showed more consistent uptake. During comparison, the technetium-labeled SPECT ligand proved as similarly effective as the two PET ligands for diagnostic imaging.

A novel method in myocardial injury risk stratification using intravenous fat emulsion as sole rapid preparation for unfasted patients to suppress myocardial 18F-fluorodeoxyglucose uptake for optimal cardiac PET imaging: a proof-of-concept randomized-crossover trial.

Optimal imaging of ischemic or inflammed myocardium via 18F-FDG PET imaging requires suppression of background carbohydrate metabolism in normal myocardium. Sole administration of intravenous lipid emulsion has not previously been used to rapidly prepare unfasted patients, such as in emergent clinical situations. In this proof-of-concept pilot, we posited that intravenous fat emulsion suppresses physiological metabolic uptake of in non-ischemic, non-inflammatory myocardium in unprepared and unfasted setting for enhanced cardiac positron emission tomography (PET) imaging. We conducted an ethics-approved, single-blind, prospective randomized crossover trial of 10 healthy volunteers from January 2020 to June 2021. Participants were unfasted and rendered hyperglycemic before being administered either high dose intravenous lipid emulsion-1.5 ml kg of 20% lipid emulsion, followed by 15 ml/kg/hr for 30mins-or saline prior to 18F-FDG injection and subsequent cardiac PET imaging. Assessors undertook image analysis for maximum standard uptake value (SUVmax), minimum standard uptake value (SUVmin) and qualitative assessment, and groups were compared using univariate analysis. The study population age was 44.5 years [IQR 32.5-56.5], with 50% male and a median BMI of 22.75 [IQR 25.0-28.5] kg/m2. The study was feasible and there were no adverse side effects from the interventions. In these participants with normal myocardium, 18F-FDG uptake was reduced by intravenous lipid emulsion as assessed by SUVmax and qualitative assessment (p = 0.042, r = 0.454 and p = 0.009, r = -0.581, respectively). Intravenous lipid emulsion suppresses background metabolic uptake of 18F-FDG even in unprepared and unfasted patients. Our findings prove and expand the possible applications for cardiac 18F-FDG PET in various settings, including in emergent settings as a means of rapid preparation in place of current more time-consuming standard protocols, allowing time-critical management to be effected.

Comparison of sedation and general anesthesia protocols for 18F-FDG-PET/CT studies in dogs and cats: Musculoskeletal uptake and radiation dose to workers.

In veterinary medicine, PET/CT scans are generally performed with the patient under general anesthesia. The aim of this prospective crossover study was to compare the musculoskeletal uptake of 18F-FDG and radiation doses to workers during PET/CT studies of healthy dogs and cats between sedation and general anesthesia. Volume and maximal standard uptake values (SUVmax) values of abnormal 18F-FDG uptake in the skeletal musculature, presence of misregistration artifact, and radiation doses to workers for each PET/CT study were recorded. Sedation was associated with increased volume of 18F-FDG uptake in the musculature of the thoracic limbs (p=.01), cervical (p=.02), and thoracic (p=.03) spine. Increased volume and SUVmax of the musculature assessed altogether were associated with the lighter degree of sedation (p=.04 for both). A significant decrease in the odds of misregistration artifact was observed for anesthetized animals in comparison with sedated (OR: 0.0, 95% CI: 0.0-0.0, p=.01). Radiation doses to workers were significantly higher for sedation compared with general anesthesia (p=.01) and for the anesthesia technician compared with the nuclear medicine technologist (p=.01). Use of sedation for PET/CT studies in dogs and cats is feasible. However, it is associated with increased physiologic musculoskeletal uptake of 18F-FDG in the thoracic limbs, cervical, and thoracic spine, with increased frequency of misregistration artifact, and with increased radiation doses to workers. These limitations can be overcome by recognition of the uptake pattern and monitoring/rotation of the involved staff at institutions where a high caseload is expected.

Assessing the physiological responses and uptake patterns of lanthanum and yttrium in rice and Phytolacca americana L.

The effects of rare earth elements (REEs) on plant physiology and bioaccumulation characteristics vary significantly. As a result, considerable attention has been directed towards the effects and toxicity of REEs on plants. REEs migrate and transform in the environment and are absorbed by plant roots. However, different plants exhibit varying capacities to absorb REEs, leading to diverse impacts on their growth. In our study, we subjected seedlings of rice and Phytolacca americana L. to a gradient of lanthanum and yttrium (La + Y) concentrations to evaluate the physicochemical effects and uptake patterns of these elements. We meticulously measured variables such as biomass, root length, and elemental concentrations of La and Y, as well as macronutrients (P, Na, K, Mn, Fe, Mg, Ca) and micronutrients (Cu, Zn) to decode the physiological responses to varying levels of La + Y exposure. Based on the known dualistic nature of REEs interaction with plants, our results reveal that the threshold of REEs to different plants is different, and this conclusion can serve well for the formulation of rare earth pollution remediation strategies. Importantly, the accumulation of La and Y in P. americana L. roots was significantly greater than in rice roots, by an order of magnitude, reflecting the unique uptake capacities of hyperaccumulators. Additionally, this research found that nutrient dynamics and the absorption patterns of La and Y within the plants diverged, suggesting that La uptake in P. americana L. may occur via Ca2+ ion channels. These insights enhance our understanding of REE-plant interactions and have broader implications for agriculture and environmental health.

Molybdenum Disulfide Nanoparticle Enhancing Photosynthesis in Solanum Lycopersicum

AbstractPhotosynthesis is a dynamic, complex, photo‐catalytic process that plays a key role in the growth and development of plants. It converts solar energy to chemical energy by precise organisation of light harvesting molecules in the photosynthetic system. Artificially imitating such systems is difficult due to the complexity of different cascades associated with photosynthesis. Nanoparticle mediated photocatalytic complexes have been shown to improve photosynthesis efficiency. Nanomaterials, such as molybdenum disulfide (MoS2) efficiently capture sunlight and assist in photosynthesis enhancement and nanosheets offer an additional advantage of increased surface area for sunlight harnessing. Foliar nutrition supplementation provides high yield potential to crops and their application in small doses improves the photosynthesis and elevates the plant performance. This study aims at mapping the efficiency of facile one‐pot hydrothermally synthesized MoS2 nanosheets in enhancing the photosynthetic ability of tomato plants. The treatments included the supplementation and absence of molybdenum source to plants. Physiological features (root length, shoot length, biomass), biochemical parameters (antioxidant activity), photosynthesis parameters (carbon assimilation, stomatal conductance, transpiration rate, water use efficiency, chlorophyll and carotenoid content), uptake and translocation of MoS2 nanosheets were evaluated. Increases of 22.07 %, 49.95 % and 18.56 % in net photosynthetic rate, water use efficiency and chlorophyll content respectively, were observed in MoS2_Nano treated plants compared with untreated plants. These nanosheets improved plant photosynthesis parameters and enhanced photosystem efficiency without inducing phytotoxicity. This study demonstrates the promise of such approaches towards enhanced plant photosystem efficiency, leading to improved agricultural productivity, particularly in the regions with less sunlight.

International Benchmark for Total Metabolic Tumor Volume Measurement in Baseline 18F-FDG PET/CT of Lymphoma Patients: A Milestone Toward Clinical Implementation.

Total metabolic tumor volume (TMTV) is prognostic in lymphoma. However, cutoff values for risk stratification vary markedly, according to the tumor delineation method used. We aimed to create a standardized TMTV benchmark datasetallowing TMTV to be tested and applied as a reproducible biomarker. Methods: Sixty baseline 18F-FDG PET/CT scans were identified with a range of disease distributions (20 follicular, 20 Hodgkin, and 20 diffuse large B-cell lymphoma). TMTV was measured by 12 nuclear medicine experts, each analyzing 20 cases split across subtypes, with each case processed by 3-4 readers. LIFEx or ACCURATE software was chosen according to reader preference. Analysis was performed stepwise: TMTV1 with automated preselection of lesions using an SUV of at least 4 and a volume of at least 3 cm3 with single-click removal of physiologic uptake; TMTV2 with additional removal of reactive bone marrow and spleen with single clicks; TMTV3 with manual editing to remove other physiologic uptake, if required; and TMTV4 with optional addition of lesions using mouse clicks with an SUV of at least 4 (no volume threshold). Results: The final TMTV (TMTV4) ranged from 8 to 2,288 cm3, showing excellent agreement among all readers in 87% of cases (52/60) with a difference of less than 10% or less than 10 cm3 In 70% of the cases, TMTV4 equaled TMTV1, requiring no additional reader interaction. Differences in the TMTV4 were exclusively related to reader interpretation of lesion inclusion or physiologic high-uptake region removal, not to the choice of software. For 5 cases, large TMTV differences (>25%) were due to disagreement about inclusion of diffuse splenic uptake. Conclusion: The proposed segmentation method enabled highly reproducible TMTV measurements, with minimal reader interaction in 70% of the patients. The inclusion or exclusion of diffuse splenic uptake requires definition of specific criteria according to lymphoma subtype. The publicly available proposed benchmark allows comparison of study results and could serve as a reference to test improvements using other segmentation approaches.

18F-DCFPyL PSMA PET/CT Tracheobronchial Uptake in Patients with Prostate Cancer: Incidence and Etiology.

We evaluated the incidence and potential etiology of tracheobronchial uptake in patients being evaluated by 18F-DCFPyL PET/CT for prostate cancer (PCa). Methods: The study included a consecutive 100 PCa patients referred for 18F-DCFPyL PET/CT. The PET/CT scans were retrospectively reviewed. The presence or absence of physiologic tracheobronchial uptake on PET/CT was recorded. To further evaluate tracheal prostate-specific membrane antigen (PSMA) expression, immunohistochemistry was performed on tracheal samples taken from 2 men who had surgical resection of lung cancer. Results: Tracheal uptake was present in 31 of 100 patients (31%). When tracheal uptake was present, the SUVmax was significantly higher in the left main bronchus (mean, 2.7) than in the right (mean, 2.3) (P < 0.001). Histopathologic testing of tracheobronchial samples showed PSMA expression in bronchial submucosal glands. Conclusion: In PCa patients undergoing 18F-DCFPyL PET/CT, tracheobronchial uptake occurred in 31% of patients. This is attributed to normal physiologic PSMA expression in bronchial submucosal glands.

Potential Utility of SGLT2i To Reduce Physiologic Cardiac Glucose Uptake During FDG PET Imaging

Potential Utility of SGLT2i To Reduce Physiologic Cardiac Glucose Uptake During FDG PET Imaging

64Cu]Copper chloride PET-CT: a comparative evaluation of fasting and non-fasting states in patients of prostate carcinoma.

Altered copper metabolism in cancer has been linked to increased intracellular copper uptake mediated by human copper transporter 1, with [64Cu]Cu2+ as a potential biomarker for cancer theranostics. [64Cu]CuCl2 PET-CT though explored in various malignancies, a lack of standardized protocol exists, particularly regarding fasting status before imaging. This analysis aimed to evaluate the requirement of fasting for [64Cu]CuCl2 PET-CT along with temporal changes in physiological organ uptake in delayed scans. A total of 26 patients of prostate carcinoma who underwent [64Cu]CuCl2 PET-CT imaging were divided into two groups: (1) nonfasting (n = 12) and (2) fasting (n = 14). The nonfasting group received an average dose of 350 MBq, while the fasting group received 300 MBq of [64Cu]CuCl2, and PET-CT images acquired approximately 60-90 min (1 h image) and 3-3.5 h (delayed image) after intravenous injection of the tracer. An experienced nuclear medicine physician evaluated the images for qualitative assessment between the groups. Multiple spherical regions of interest were placed at sites of physiological organ uptake of the tracer and over the diseased lesions to measure the mean SUVmax. No significant difference was observed in the qualitative assessment of the images between the two groups (except for a slight predilection towards more hepatic tracer retention observed in the fasting group), including in the delayed images. The liver demonstrated the highest tracer uptake in all patients, with a mean SUVmax of 21.5 in the fasting group and 19.7 in the nonfasting group, showing no significant difference (P = 0.32). The kidneys, intestines, and salivary glands also showed similar trends of tracer uptake in both groups. The study illustrated that the fasting or nonfasting status did not affect image quality or semiquantitative measurements significantly in physiological organs and diseased lesions in patients with carcinoma prostate.

Role of Textural Analysis Parameters Derived from FDG PET/CT in Diagnosing Cardiac Sarcoidosis

Abstract Introduction Texture and radiomic analysis characterize the lesion's phenotype and evaluate its microenvironment in quantitative terms. The aim of this study was to investigate the role of textural features of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT) images in differentiating patients with cardiac sarcoidosis (CS) from patients with physiologic myocardial uptake. Methods This is a retrospective, single-center study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients. These patients underwent FDG PET/CT for the diagnosis of CS. The non-CS group underwent 18F-FDG PET/CT for other oncological indications. The PET/CT images were then processed in a commercially available textural analysis software. Region of interest was drawn over primary tumor with a 40% threshold and was processed further to derive 92 textural and radiomic parameters. These parameters were then compared between the CS group and the non-CS group. Receiver operating characteristics (ROC) curves were used to identify cutoff values for textural features with a p-value &lt; 0.05 for statistical significance. These parameters were then passed through a principle component analysis algorithm. Five different machine learning classifiers were then tested on the derived parameters. Results A retrospective study of 67 patients, 17 diagnosed CS patients, and 50 non-CS patients, was done. Twelve textural analysis parameters were significant in differentiating between the CS group and the non-CS group. Cutoff values were calculated for these parameters according to the ROC curves. The parameters were Discretized_HISTO_Entropy, GLCM_Homogeneity, GLCM_Energy, GLRLM_LRE, GLRLM_LGRE, GLRLM_SRLGE, GLRLM_LRLGE, NGLDM_Coarseness, GLZLM_LZE, GLZLM_LGZE, GLZLM_SZLGE, and GLZLM_LZLGE. The gradient boosting classifier gave best results on these parameters with 85.71% accuracy and an F1 score of 0.86 (max 1.0) on both classes, indicating the classifier is performing well on both classes. Conclusion Textural analysis parameters could successfully differentiate between the CS and non-CS groups noninvasively. Larger multicenter studies are needed for better clinical prognostication of these parameters.

Physiological biodistribution on Ga68-PSMA PET/CT and the factors effecting biodistribution

AimThe study aims to determine the physiological and pathophysiological distribution of the radiopharmaceutical (Ga68-PSMA-617) and investigate whether there are differences in distribution according to the laboratory, histopathological and clinical findings that can affect image evaluation. Also, we aimed to determine cut-off values to distinguish physiological and pathological uptake in prostate, bone, and lymph nodes.Materials and Methods229 prostate cancer patients who underwent Ga68-PSMA PET/CT at our department were retrospectively analyzed. The patients were grouped according to PET/CT results, Gleason scores, PSA values, received treatments, metastatic status and other laboratory values. The SUV values of the organs, tissues, and pathological lesions of the patients in these subgroups were compared among themselves.ResultsNo significant difference was detected in the physiological uptake of lymph nodes and bone between the groups. In the group with patients that received androgen deprivation therapy (ADT), the bone metastasis SUV values were found to be higher and the SUV values of the submandibular gland and renal cortex were found to be lower (Mann–Whitney U, p = 0.043; 0.004; 0.01, respectively). In the group with patients who received radiotherapy, the normal prostate tissue SUV values were determined to be higher (Mann–Whitney U, p = 0.009). The SUV values of the submandibular gland, muscle, liver, and blood pool were found to be lower in the group of patients with high serum LDH values. The cut-off SUVmax value was determined to be 6.945 (sensitivity 89.6%, specificity 98.1%) for primary prostate lesion; 4.72 for lymph node metastasis; 4.25 for bone metastasis. The serum PSA cut-off value to distinguish the negative/positive groups was found to be 1,505 (sensitivity 79.7%, specificity 77.3%).ConclusionIn conclusion, PSMA-617 demonstrates a similar biodistribution with other PSMA ligands. The physiological uptake of lymph nodes and bone which are mostly metastasized in prostate cancer, are not affected by the factors we examined. It should be kept in mind that the normal prostate tissue uptake may increase in patients receiving radiotherapy, and the physiological/pathological uptake of the organs may differ due to the changes in PSMA expression in patients receiving ADT, tumor burden, and kidney function may affect the biodistribution.

Incidental Visualization of Gallbladder on Post-therapy [177Lu]Lu-DOTATATE Scintigraphy Mimicking a Liver Metastasis in a Duodenal Neuroendocrine Tumor

AbstractWe present a rare case of physiological uptake of [177Lu]Lu-DOTATATE in the gallbladder, observed post-therapy, in a 47-year-old man with grade I duodenal neuroendocrine tumor (NET), despite no uptake being observed pre-therapy in the somatostatin receptor-positron emission tomography. On planar scintigraphy, the gallbladder uptake could have been misidentified as liver metastasis. By utilizing single photon emission computed tomography/computed tomography imaging, we were able to precisely localize the tracer and obtain anatomical morphological characteristics, thereby averting the potential for misinterpretation of liver metastasis resulting from the gallbladder's physiological uptake of [177Lu]Lu-DOTATATE in NET patients.

Chemokine Receptor-4 Targeted PET/CT Imaging with 68Ga-Pentixafor in Head and Neck Cancer-A Comparison with 18F-FDG and CXCR4 Immunohistochemistry.

Head and neck squamous cell carcinoma (HNSCC) is common, and its incidence is increasing, particularly in HIV-infected individuals who present with more aggressive disease. Despite aggressive treatment, the prognosis remains poor because of resistance to chemoradiation therapy. So far, studies report very low [68Ga]Ga-Pentixafor avidity in HNSCC. This study investigated the diagnostic performance of CXCR4-directed imaging of carcinoma of the oral cavity, oropharynx, and nasopharynx with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Ga-Pentixafor and explored its ability to quantify CXCR4 expression in vivo. In this prospective cross-sectional study, twenty-three (23) patients aged 52.9 ± 10.4 (19.6), 17 males and 6 females with primarily diagnosed (n = 17) or pre-treated (n = 6) SCC of the oral cavity (OCSCC, n = 11), oropharynx (OPSCC, n = 9), nasopharynx (NPSCC, n = 2) and unknown primary (n = 1) underwent imaging with [68Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([18F]F-FDG) served as a standard reference. All lesions were visually rated using a 5-point Likert scale. For both tracers, maximum standardized uptake values (SUVmax) and the total lesion uptake (TLU) were recorded and compared using the Wilcox-signed rank test. In addition, the tumor-to-background ratios were derived using the liver (TLR), spleen (TSR), and posterior cervical muscles (TMR) as background. The relationships between the SUVs of the two tracers were assessed using the Spearman correlation. CXCR4 immunohistochemistry (IHC) staining was correlated with 68Ga-Pentixafor-PET/CT in 21/23 patients. Ninety-one percent (21/23) of tumors were visually detected on [68Ga]Ga-Pentixafor; however, [68Ga]Ga-Pentixafor was less intense compared with [18F]F-FDG-PET. Quantitative analysis showed higher [18F]F-FDG SUVmax in comparison with [68Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, p = 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, p < 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 p = 0.014. Nasopharyngeal cancer demonstrated more intense tracer accumulation than oropharyngeal and oral cavity malignancies. CXCR4 IHC staining was positive in 15/21 patients, and there was a statistically significant correlation between IHC staining and [68Ga]Ga-Pentixafor SUVmean r = 0.5 p = 0.027, and performance status r = 0.83 p = 0.0104. In conclusion, although [68Ga]Ga-Pentixafor cannot replace [18F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted 68Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of 68Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [68Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [18F]F-FDG PET/CT imaging.

Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. ClinicalTrials.gov identifier NCT06056362.

68Ga]Ga-ABY-025 PET in HER2-positive breast cancer: Benefits and pitfalls in staging of axillary disease.

1035 Background: [68Ga]Ga-ABY-025 PET showed promising results in quantifying human epidermal growth factor receptor Type 2 (HER2) expression in breast cancer patients [1]. In this study we extend the findings from [68Ga]Ga-ABY-025 PET with data from both treatment-naïve patients and previously treated patients with recurrences, mimicking the clinical situation other sites might encounter when HER2-targeting imaging is made more widely available. The focus of this additional data analysis is on staging, potential pitfalls and changes in uptake patterns associated with previous treatments. Methods: [68Ga]Ga-ABY-025 PET and [18F]-FDG PET images from 50 women with biopsy confirmed HER2 positive breast cancer were examined. Each patient underwent both scans within 1 week. A follow-up [18F]-FDG PET was performed after 2 courses of HER2-targeted treatment to assess metabolic response. Results: Twelve out of 50 patients showed heterogeneous [68Ga]Ga-ABY-025 uptake. Three out of these 12 patients presented with a wider local spread that was only detectable using [68Ga]Ga-ABY-025 PET as distinct uptake in lymph nodes of 2-5 mm size. Based on the additional information from [68Ga]Ga-ABY-025 PET, restaging was evaluated in two of the three cases, both of which had lobular carcinoma, and resulted in modifications in treatment plans. Two patients who received COVID-19 vaccine closely before undergoing PET scans showed high uptake on [18F]-FDG PET in lymph nodes ipsilateral to the vaccine injection site, but not on [68Ga]Ga-ABY-025 PET. Additionally, the physiological [68Ga]Ga-ABY-025 uptake in thyroid gland and axillary sweat glands was inversely correlated with the number of previous treatments and was significantly more pronounced in treatment-naïve patients. Conclusions: [68Ga]Ga-ABY-025 PET provided additional information that, in conjunction with [18F]-FDG PET findings, might help in accurate staging, particularly in cases with very small lymph node metastases. It also helped reduce false positive results as [68Ga]Ga-ABY-025 uptake was so far not seen in any benign inflammatory lesions. Physiological uptake can be seen in thyroid and apocrine glandular tissues but gradually disappear with subsequent HER2-targeted therapies. 1,Alhuseinalkhudhur, A. et al. J Nucl Med, 2023 64(9): p. 1364-1370. Clinical trial information: NCT03655353 .

An Analysis of the Physiological and Psychological Responses Elicited When Wearing an Aerogel Cold Protective Jacket in Airflow

This study evaluated the thermal physiological and psychological responses elicited when wearing cold protective jackets with aerogel fillings in two cold environments, one without air velocities and one with air velocities (2.3 m·s-1), at an air temperature of 10°C. The participants were five healthy young males. Measures were taken of physiological parameters, blood pressure (BP), heart rate (HR), core temperature, oxygen uptake (Vo2), and microclimate (temperature and humidity). The psychological parameters evaluated were thermal and wetness sensation. No differences were observed in systolic blood pressure, heart rate, and oxygen intake between the conditions. At tympanic temperature, a significant difference was observed between the conditions during exercise (p &lt;.05); . A significant difference was observed in the microclimate temperature of the clothing according to the airflow, and temperature changes in the chest and back revealed different patterns. Significant differences were observed in thermal sensation (whole body (p &lt;.05), chest (p &lt;.05), back (p &lt;.01)) between airflow conditions. The results therefore indicate that cold protective jackets with an aerogel filling are suitable for people operating in low-temperature and airflow environments.

The effect of hormone therapy on physiological uptake of the endometrium on [18F]F-FDG PET in postmenopausal women.

The effects of hormonal therapy, estrogen-based hormone replacement therapy (HRT), and anti-tumor hormone therapy, such as tamoxifen, on the physiological uptake of the endometrium on 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) positron emission tomography (PET) in postmenopausal women have not been determined. We explored the effect of hormone therapy, particularly HRT, on physiological uptake in the endometrium of postmenopausal women. Postmenopausal women receiving hormone therapy who underwent cancer screening using PET/computed tomography (CT) between June 2016 and April 2023 were included in the hormone therapy group (n = 21). Postmenopausal women with no history of hormone therapy were included in the control group (n = 49). First, the physiological endometrial uptake at menopausal age and at least 1year thereafter was compared quantitatively (SUVmax) and qualitatively (4-point scale) in the control group, to assess when the endometrium ceased to show significant physiological [18F]F-FDG uptake after menopause. Endometrial uptake was compared between the hormone therapy and control groups. The association between HRT duration (months) and endometrial uptake (SUVmax) was evaluated. Endometrial thickness, measured using transvaginal ultrasonography, was also compared between the two groups. Endometrial uptake was significantly reduced both qualitatively and quantitatively (P < 0.05) at least 1year after menopause in control patients, by which time most women (89.8%) no longer had significant endometrial uptake. The hormone therapy group (n = 21) showed higher FDG uptake in the endometrium compared to the control group (median SUVmax: 2.3 vs 1.9, P = 0.0011), as well as a higher visual score (P < 0.0001). HRT duration did not correlate with endometrial uptake (P = 0.097). Endometrial thickness in the hormone therapy group was significantly thicker than in the control group (median: 3.9mm vs 1.8mm, P = 0.002). Hormone therapy may affect physiological uptake in the endometrium in postmenopausal women.

Abstract PS05-04: [89Zr]Trastuzumab-PET/MRI to Characterize HER2+ Breast Cancer: A Quantitative Approach on Tumor Heterogeneity

Abstract Introduction: Molecular imaging of human epidermal receptor 2 (HER2) aims to overcome limitations of traditional HER2 assessment through biopsy, including invasiveness and inability to detect intra and inter-tumoral spatial heterogeneity. Prior human studies suggest that [89Zr]Trastuzumab-positron emission tomography (PET) imaging can effectively differentiate HER2 lesions (Dehdashti et al, Breast Cancer Res. Treat. 2018). Commonly, CT complements PET for anatomical reference, however, integrating MRI enables the sensitivity of soft-tissue contrast required for anatomic and morphological breast imaging and can provide for quantitative multiparametric characterization. Diffusion weighted-MRI (DW-MRI) contributes to tumor characterization by assessing intratumoral cellularity via the apparent diffusion coefficient (ADC), and can be combined with molecular expression from HER2-PET. We present preliminary results in 13 patients with HER2 PET/MRI to define tumor and normal tissue imaging metrics. Methods: A phase II clinical trial assessing the feasibility of [89Zr]trastuzumab-PET with simultaneous quantitative DW-MRI to enhance understanding of tumor heterogeneity in patients with HER2-positive metastatic breast cancer. 13 patients (ages 40-70; mean 60) with HER2-positive breast cancer based on prior biopsy underwent whole-body [89Zr]trastuzumab-PET/MR imaging (5 ± 1 days post-injection of radiopharmaceutical) during the course of HER2-directed therapy. Normal organ and tumor regions of interest (ROI) were identified on concurrently acquired whole-body T1-weighted MRI for ADC (cellularity) and standardized uptake value (SUV, PET uptake) mean quantification. Tumor presence was confirmed via bone scintigraphy, FDG-PET/CT, or contrast-enhanced MRI. Non-parametric T-tests compared lesions to normal organs. Lesions greater than 30 mm in diameter underwent multiparametric intratumoral habitat analysis. Using the median HER2 values, tumors were evaluated for heterogeneity of high and low HER2 expression in conjunction with ADC. Long-term treatment response evaluation is ongoing. Results: Mean [89Zr]trastuzumab uptake, SUV, and ADC values for normal tissue were summarized in Table 1. All tumors demonstrated higher overall uptake of [89Zr]trastuzumab (bone: p=0.019, brain: p=0.014, breast: p=0.069, juxtapulmonary: p=0.026) and increased ADCmean values (bone: p=0.002, brain: p=0.5, breast: p=0.03, juxtapulmonary: p=0.037), in comparison to matched normal organs. Notably, one of five patients with a breast lesion, who completely responded to HER2 targeted therapy, exhibited the highest breast lesion SUVmean. Brain and lymph node lesions demonstrated intratumoral heterogeneity of HER2 expression. Conclusion: Our study demonstrates the potential value of quantitative MRI along with molecular imaging to characterize metastatic HER2+ breast cancer and evaluate intratumoral heterogeneity. We underscore the importance of standardizing processing techniques and contribute to this effort by summarizing [89Zr]trastuzumab uptake and cellularity values of normal physiological uptake. Higher SUVmean and ADC mean values observed in lesions, compared to normal tissue, highlight their potential roles in intratumoral classification. While studies have shown the utility of [89 Zr]trastuzumab-PET/CT, our findings demonstrate that integrated DW-MRI can aid in tumor classification. Table 1: Physiological 89Zr-Trastuzumab Uptake (SUVmean) and Apparent Diffusion Coefficient (ADCmean) in Healthy Tissues Citation Format: Ameer Mansur, Moozhan Nikpanah, Johnathan McConathy, Erica Stringer-Reasor, Gabrielle Rocque, Ahmed Elkhanany, Katia Khoury, Nusrat Jahan, Suzanne Lapi, Anna Sorace. [89Zr]Trastuzumab-PET/MRI to Characterize HER2+ Breast Cancer: A Quantitative Approach on Tumor Heterogeneity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-04.

Reducing False-Positives Due to Urinary Stagnation in the Prostatic Urethra on 18 F-DCFPyL PSMA PET/CT With MRI.

Prostate-specific membrane antigen (PSMA)-targeting PET radiotracers reveal physiologic uptake in the urinary system, potentially misrepresenting activity in the prostatic urethra as an intraprostatic lesion. This study examined the correlation between midline 18 F-DCFPyL activity in the prostate and hyperintensity on T2-weighted (T2W) MRI as an indication of retained urine in the prostatic urethra. Eighty-five patients who underwent both 18 F-DCFPyL PSMA PET/CT and prostate MRI between July 2017 and September 2023 were retrospectively analyzed for midline radiotracer activity and retained urine on postvoid T2W MRIs. Fisher's exact tests and unpaired t tests were used to compare residual urine presence and prostatic urethra measurements between patients with and without midline radiotracer activity. The influence of anatomical factors including prostate volume and urethral curvature on urinary stagnation was also explored. Midline activity on PSMA PET imaging was seen in 14 patients included in the case group, whereas the remaining 71 with no midline activity constituted the control group. A total of 71.4% (10/14) and 29.6% (21/71) of patients in the case and control groups had urethral hyperintensity on T2W MRI, respectively ( P < 0.01). Patients in the case group had significantly larger mean urethral dimensions, larger prostate volumes, and higher incidence of severe urethral curvature compared with the controls. Stagnated urine within the prostatic urethra is a potential confounding factor on PSMA PET scans. Integrating PET imaging with T2W MRI can mitigate false-positive calls, especially as PSMA PET/CT continues to gain traction in diagnosing localized prostate cancer.

Vision transformer to differentiate between benign and malignant slices in 18F-FDG PET/CT

Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is widely used for the detection, diagnosis, and clinical decision-making in oncological diseases. However, in daily medical practice, it is often difficult to make clinical decisions because of physiological FDG uptake or cancers with poor FDG uptake. False negative clinical diagnoses of malignant lesions are critical issues that require attention. In this study, Vision Transformer (ViT) was used to automatically classify 18F-FDG PET/CT slices as benign or malignant. This retrospective study included 18F-FDG PET/CT data of 207 (143 malignant and 64 benign) patients from a medical institute to train and test our models. The ViT model achieved an area under the receiver operating characteristic curve (AUC) of 0.90 [95% CI 0.89, 0.91], which was superior to the baseline Convolutional Neural Network (CNN) models (EfficientNet, 0.87 [95% CI 0.86, 0.88], P < 0.001; DenseNet, 0.87 [95% CI 0.86, 0.88], P < 0.001). Even when FDG uptake was low, ViT produced an AUC of 0.81 [95% CI 0.77, 0.85], which was higher than that of the CNN (DenseNet, 0.65 [95% CI 0.59, 0.70], P < 0.001). We demonstrated the clinical value of ViT by showing its sensitive analysis of easy-to-miss cases of oncological diseases.