Fibroblast Activation Protein-Targeted Radioligand Therapy with 177Lu-EB-FAPI for Metastatic Radioiodine-Refractory Thyroid Cancer: First-in-Human, Dose-Escalation Study.

PURPOSE: Fibroblast activation protein (FAP) is a promising target for tumor treatment. In this study, we aimed to investigate the safety and efficacy of the albumin binder-conjugated FAP-targeted radiopharmaceutical, 177Lu-EB-FAPI (177Lu-LNC1004), in patients with metastatic radioiodine-refractory thyroid cancer (mRAIR-TC). PATIENTS AND METHODS: This open-label, non-randomized, first-in-human, dose-escalation, investigator-initiated trial had a 3+3 design and involved a 6-week 177Lu-LNC1004 treatment cycle in patients with mRAIR-TC at 2.22 GBq initially, with subsequent cohorts receiving an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed. RESULTS: 177Lu-LNC1004 administration was well tolerated, with no life-threatening adverse events observed. No patients experienced DLT in Group A (2.22 GBq/cycle). One patient experienced grade 4 thrombocytopenia in Group B (3.33 GBq/cycle); hence, another three patients were enrolled, none of whom experienced DLT. Two patients experienced grade 3 and 4 hematotoxicity in Group C (4.99 GBq/cycle). The mean whole-body effective dose was 0.17 ± 0.04 mSv/MBq. Intense 177Lu-LNC1004 uptake and prolonged tumor retention resulted in high mean absorbed tumor doses (8.50 ± 12.36 Gy/GBq). The mean effective half-lives for the whole-body and tumor lesions were 90.20 ± 7.68 and 92.46 ± 9.66 hours, respectively. According to RECIST, partial response, stable disease, and progressive disease were observed in 3 (25%), 7 (58%), and 2 (17%) patients, respectively. The objective response and disease control rates were 25% and 83%, respectively. CONCLUSIONS: FAP-targeted radioligand therapy with 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated in patients with advanced mRAIR-TC, with high radiation dose delivery to the tumor lesions, encouraging therapeutic efficacy, and acceptable side effects.

Zerovalent Iron/Cu Combined Degradation of Halogenated Disinfection Byproducts and Quantitative Structure-Activity Relationship Modeling.

Previous studies have reported that zerovalent iron (ZVI) can reduce several aliphatic groups of disinfection byproducts (DBPs) (e.g., haloacetic acids and haloacetamides) effectively, and the removal efficiency can be significantly improved by metallic copper. Information regarding ZVI/Cu combined degradation of different types of halogenated DBPs can help understand the fate of overall DBPs in drinking water distribution and storage systems consisting of unlined cast iron/copper pipes and related potential control strategies. In this study, we found that, besides aliphatic DBPs, many groups of new emerging aromatic DBPs formed in chlorinated and chloraminated drinking water can be effectively degraded by ZVI/Cu; meanwhile, total organic halogen and total ion intensity were reduced significantly after treatment. Moreover, a robust quantitative structure-activity relationship model was developed and validated based on the ZVI/Cu combined degradation rate constants of 14 typical aromatic DBPs; it can predict the degradation rate constants of other aromatic DBPs for screening and comparative purposes, and the optimized descriptors indicate that DBPs possessing a lower value of the lowest unoccupied molecular orbital energy and a higher value of dipole moment tend to present higher degradation rate constants. In addition, toxicity data of 47 DBPs (belonging to 18 groups) were predicted by two previously established toxicity models, demonstrating that, although most DBPs exhibit higher toxicity than their dehalogenated products, some DBPs show lower toxicity than their lowly halogenated analogs.

A retrospective analysis of MS/MS screening for IEM in high-risk areas.

Inborn errors of metabolism (IEM) can lead to severe motor and neurological developmental disorders and even disability and death in children due to untimely treatment. In this study, we used tandem mass spectrometry (MS/MS) for primary screening and recall of those with positive primary screening for rescreening. Further diagnosis was based on biochemical tests, imaging and clinical presentation as well as accurate genetic testing using multi-gene panel with high-throughput sequencing of 130 IEM-related genes. The screening population was 16,207 newborns born between July 1, 2019, and December 31, 2021. Based on the results, 8 newborns were diagnosed with IEM, constituting a detection rate of 1:2,026. Phenylketonuria was the most common form of IEM. In addition, seven genes associated with IEM were detected in these eight patients. All eight patients received standardized treatment starting in the neonatal period, and the follow-up results showed good growth and development. Therefore, our study suggests that MS/MS rescreening for IEM pathogenic variants in high-risk areas, combined with a sequencing validation strategy, can be highly effective in the early detection of affected children. This strategy, combined with early intervention, can be effective in preventing neonatal morbidity and improving population quality.

68Ga Fibroblast Activation Protein Inhibitor PET/CT in the Detection of Metastatic Thyroid Cancer: Comparison with 18F-FDG PET/CT.

Background Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) has been proposed as a potential radiotracer for visualizing cancerous lesions, but its utility for identifying metastatic differentiated thyroid cancer (DTC) is not well established in the literature. Purpose To evaluate the clinical utility of 68Ga-FAPI PET/CT for detecting metastatic DTC and to compare the results with those of fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods Participants with clinically suspected or confirmed metastatic DTC were prospectively enrolled and underwent paired 68Ga-FAPI and 18F-FDG PET/CT from May to August 2020. Histopathologic results and clinical follow-up (mean, 12 months ± 0.7 [SD]; range, 11-13 months) were used as reference standards for the final diagnosis. 18F-FDG and 68Ga-FAPI uptake was compared by using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic accuracy of the two techniques, and the influence of various clinicopathologic characteristics on 18F-FDG and 68Ga-FAPI uptake was evaluated with Mann-Whitney and Kruskal-Wallis tests. Results In total, 35 participants (median age, 44 years; IQR, 28-58 years; 18 [51%] men) were evaluated. In all 35 participants, the 68Ga-FAPI-derived maximum standardized uptake value (SUVmax) was higher than the 18F-FDG-derived SUVmax in the metastatic lateral compartment (6.0 vs 3.5; P = .001), axillary (8.5 vs 4.3; P = .01), mediastinal lymph nodes (9.1 vs 5.0; P = .001), and pulmonary metastases (1.7 vs 1.1; P = .004). 68Ga-FAPI PET/CT had a higher sensitivity than 18F-FDG PET/CT for depicting neck lesions (83% [65 of 78; 95% CI: 73, 90] vs 65% [51 of 78; 95% CI: 54, 75], P = .01) and distant metastases (79% [87 of 110; 95% CI: 71, 86] vs 59% [65 of 110; 95% CI: 50, 68], P < .001). Conclusion Gallium 68-labeled fibroblast activation protein inhibitor PET/CT was superior to fluorine 18 fluorodeoxyglucose PET/CT for depicting metastatic differentiated thyroid cancer, especially in lymph nodes and pulmonary metastases. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177 Lu-FAPI-46.

ABSTRACT: Many recent studies began to explore the therapeutic potential of FAP-targeted radionuclide therapy for refractory cancers. In this case, we presented the experience of multiple cycles of 177 Lu-FAPI-46 radionuclide therapy in a 34-year-old man with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Intense radiotracer uptake was observed in RAIR-DTC metastatic lesions on the pretreatment 68 Ga-FAPI PET/CT and posttherapeutic scintigraphy. Follow-up examinations after 4 cycles of 177 Lu-FAPI-46 treatment revealed stable metastatic lesions, resulting in stable disease. This case demonstrated the potential feasibility of 177 Lu-FAPI-46 in the treatment of advanced RAIR-DTC; further research on improving the FAP-targeting vector may be necessary.

68Ga-FAPI PET/CT Versus 18F-FDG PET/CT for Detecting Metastatic Lesions in a Case of Radioiodine-Refractory Differentiated Thyroid Cancer.

ABSTRACT: 18F-FDG PET/CT is a useful imaging modality for detecting disease recurrence and metastases in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). However, the sensitivity of 18F-FDG PET/CT in RAIR-DTC is not very satisfactory. 68Ga-FAPI is a promising PET tracer that allowed imaging of various types of cancer. In this case, 68Ga-FAPI showed a far better signal-to-background ratio than 18F-FDG for detecting the RAIR-DTC metastatic lesions, especially for detecting the small pulmonary metastases. Therefore, 68Ga-FAPI may be a promising alternative to 18F-FDG for detecting tumor recurrence and metastases in RAIR-DTC. It could also be used for guiding FAP-targeted radionuclide therapy.

Species and formation characteristics of halogenated DBPs in chloramination of tannic acid after biodegradation.

Tannic acid is widely found in source water and wastewater, and it is also a typical degradation precursor of natural organic matter. In this study, focused on chloramination, the formation characteristics of halogenated DBPs from tannic acid biodegradation products were examined. Fifty-nine polar emerging DBPs (including four nitrogenous DBPs) were detected and forty of them were identified for the first time; meanwhile, their formation pathways were tentatively proposed. In general, much more polar emerging DBPs were formed at the early biodegradation stage than those at the later stage, while commonly observed aliphatic DBPs presented an exactly inverse trend, because initially-formed emerging DBPs can be transformed to those aliphatic DBPs by residual chloramine. Interestingly, while the relative formation level of brominated species in overall halogenated polar emerging DBPs maintained at high level at the later biodegradation stage during chlorination, it decreased significantly later during chloramination. The discrepancy may be due to that hydrolysis effects became dominant at this period in chloramination, whereas DBP formation from the reactions between slow reactive sites and hypohalous acids prevailed in chlorination. In addition, the calculated toxicity drivers among the 21 aliphatic DBPs were found to be haloacetonitriles, although they contribute mildly to the total concentration.

68Ga-FAPI PET/CT in Thyroid Cancer With Thyroglobulin Elevation and Negative Iodine Scintigraphy.

ABSTRACT: Differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy (TENIS) syndrome is a diagnostic and therapy dilemma. In this study, we present a case of TENIS with detectable metastases in the larynx and lung on the CT scan. 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT was performed for further detection of tumor recurrence and metastases, which showed intense 68Ga-FAPI activity in the metastatic lesions. To the best of our knowledge, this is the first case of TENIS presenting with FAPI-avid metastatic lesions, demonstrating its usefulness for localizing recurrent or metastatic lesions in patients with TENIS.

Quantitative evaluation of salivary gland scintigraphy in Sjögren's syndrome: comparison of diagnostic efficacy and relationship with pathological features of the salivary glands.

OBJECTIVE: The value of salivary gland scintigraphy (SGS) in the evaluation of Sjögren's syndrome (SS) remains controversial. The aim of this study was to evaluate the diagnostic efficacy of quantitative SGS in patients with xerostomia and to assess the correlation between scintigraphic parameters and pathological features of salivary glands. METHODS: Medical records of 165 patients with xerostomia who underwent [99mTc] pertechnetate SGS and labial biopsy were retrospectively reviewed. The maximum accumulation ratio (MAR), maximum secretion ratio (MSR), and time interval from stimulation to minimum count (Tmin) of the parotid glands were calculated to quantify the glandular activity. Furthermore, pre-stimulatory oral activity index (PRI) and post-stimulatory oral activity index (POI) were calculated to quantify the oral activity. RESULTS: All parameters except for Tmin were significantly lower in patients with SS than in those without SS. Among the five SGS parameters, PRI showed the highest areas under the curve value (0.9005; p < 0.001), and PRI > 32.75 was associated with a sensitivity of 78.5% and specificity of 86.4% for the diagnosis of SS. A decrease in MAR, MSR, PRI, and POI and an increase in Tmin correlate significantly with the histopathologic grade of labial gland biopsy and disease severity of SS. No significant differences in glandular parameters (MAR, MSR, and Tmin) were found between the non-SS and early-stage SS groups. CONCLUSION: Conventional scintigraphic parameters could be used as simple, reliable, and sensitive indicators for the early diagnosis of SS and determination of disease severity.

Detection of the three-dimensional trajectory of an object based on a curved bionic compound eye.

Biological compound-eye systems have unique advantages in three-dimensional (3D) positioning based on light energy distribution. A curved compound eye was designed and manufactured to imitate a biological compound eye. To overcome the nonuniform off-axis response and enlarge the aperture of the eyelet, a novel dome light cone was designed. The dome light cone was designed as a conical structure, which consisted of a lot of fiber wires with a diameter of 6 µm. Additionally, based on the proposed biological compound-eye systems, an algorithm was proposed to obtain the 3D position of the object by analyzing the light location and intensity distribution. The effect of the illumination intensity, the position of the target's center, and the non-repeatability were evaluated. The relative standard uncertainty in the 3D position was estimated to be 8.6%. Low uncertainty verified the validity of the 3D localization algorithm.

Differential diagnostic value of 18F-FDG PET/CT for benign and malignant vertebral compression fractures: comparison with magnetic resonance imaging.

PURPOSE: The purpose of this study was to evaluate the differential diagnostic value of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for benign and malignant vertebral compression fractures (VCFs), where the diagnostic accuracy of 18F-FDG PET/CT was compared with magnetic resonance imaging (MRI). PATIENTS AND METHODS: Between 2015 and 2017, we retrospectively evaluated 87 patients with 116 VCFs. MRI was performed in all the 87 patients, whereas 18F-FDG PET/CT was executed in 51 patients. Three malignant features (convex posterior cortex, epidural mass formation, and pedicle enhancement) from MRI and the maximum standardized uptake value (SUVmax) from 18F-FDG PET/CT were evaluated in benign and malignant VCFs, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value of MRI and 18F-FDG PET/CT were compared in the differentiation of malignant from benign VCFs. RESULTS: The results of our investigation showed that the sensitivity and specificity for predicting malignant VCFs were 75.6% and 77.3% for convex posterior cortex, 82.9% and 813% for epidural mass formation, and 85.7% and 70.8% for pedicle enhancement. 18F-FDG PET/CT demonstrated higher sensitivity (100%) but lower specificity (38.9%) as compared to MRI with regard to differentiation between benign and malignant VCFs. A significant difference in the SUVmax values was observed between the benign and malignant fractures (2.9 ± 1.0 vs 5.0 ± 1.8, P < 0.01). Besides the value of SUVmax, it has been noticed that the FDG uptake pattern differed in malignant and benign fractures. CONCLUSION: Significant MRI findings such as convex posterior cortex, epidural mass formation, and pedicle enhancement are highly suggestive of malignancy. 18F-FDG PET/CT reliably differentiated the fractures of malignant from benign based on both SUVmax and 18F-FDG uptake pattern. In a situation where MRI findings are not diagnostic, 18F-FDG PET/CT provides additional information as it has high sensitivity and is semiquantitative.

Effect of local mild hypothermia on regional cerebral blood flow in patients with acute intracerebral hemorrhage assessed by 99mTc-ECD SPECT imaging.

OBJECTIVE: This study aimed to observe the effect of local mild hypothermia on regional cerebral blood flow (rCBF) after acute intracerebral hemorrhage (ICH) and to evaluate its relation to clinical outcome in patients with ICH. METHODS: 36 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were randomly assigned to 2 group: local mild hypothermia with conventional mannitol (Group A) or conventional mannitol (Group B). SPECT study was performed at day 7 after therapy. The SPECT images were semi-quantitatively analyzed, and the radioactivity ratios of lesion to normal tissue (L/NT) were calculated. National Institutes of Health Stroke Scale (NIHSS) were used in evaluation at days 14 and 21 after therapy. RESULTS: There were significant differences in NIHSS score at days 14 and 21, and the L/NT ratios between the groups A and B (P < 0.05). Based on GCS, more patients in the group A showed favorable outcomes than patients in the group B (P < 0.05). Furthermore, the L/NT ratios significantly increased in patients with favorable outcomes compared to poor outcomes. Changes in NIHSS score at days 14 and 21 were closely negatively correlated with the L/NT ratios in the groups A and B (r= -0.58, -0.61, and -0.52, -0.75, respectively, P < 0.05). CONCLUSION: Local mild hypothermia could significantly increase rCBF and improve clinical outcome in ICH patients as evaluated by ^{99m}Tc-ECD SPECT study.

Multiplex immunodetection of tumor markers with a suspension array built upon core-shell structured functional fluorescence-encoded microspheres.

A new suspension array built upon laboratory-prepared functional fluorescence-encoded polystyrene beads (FFPBs) was developed for multiplex immunodetection of tumor markers. The FFPBs were synthesized by copolymerizing rhodamine 6G (R6G) and carboxyl function groups on the surface of the seed beads forming a core-shell structure. The fabrication process was facile and the encoding fluorescence intensity of the beads can be precisely controlled by adjusting the quantity of R6G. In present work, we demonstrated that the quantity variation of impregnated R6G had negligible effect on the coupling efficiency of biomolecules onto the surface of the FFPBs. The R6G encoding fluorescence remained good monodispersity upon capture probe coupling and immunocomplex formation. No fluorescence resonance energy transfer was observed between the R6G doped in the bead shell and fluorophore used for antibody labeling. Under the optimal conditions, the proposed suspension array allowed simultaneous detection of alpha-fetoprotein, carcinoembryonic antigen, and prostate specific antigen in the ranges of 0.07-500 ng mL(-1), 1-2000 ng mL(-1), and 0.5-500 ng mL(-1), respectively, with detection limits of 0.0626 ng mL(-1), 0.554 ng mL(-1), and 0.250 ng mL(-1). Test on clinical serum samples demonstrated that the results obtained with suspension array were in good agreement with those of the reference electrochemiluminescence immunoassay method. We conclude that the laboratory-made FFPBs are sufficient as the microcarrier for the construction of suspension array in clinical diagnosis.