Controlling Molecular Photoisomerization in Photonic Cavities through Polariton Funneling.

Strong coupling between photonic modes and molecular electronic excitations, creating hybrid light-matter states called polaritons, is an attractive avenue for controlling chemical reactions. Nevertheless, experimental demonstrations of polariton-modified chemical reactions remain sparse. Here, we demonstrate modified photoisomerization kinetics of merocyanine and diarylethene by coupling the reactant's optical transition with photonic microcavity modes. We leverage broadband Fourier-plane optical microscopy to noninvasively and rapidly monitor photoisomerization within microcavities, enabling systematic investigation of chemical kinetics for different cavity-exciton detunings and photoexcitation conditions. We demonstrate three distinct effects of cavity coupling: first, a renormalization of the photonic density of states, akin to a Purcell effect, leads to enhanced absorption and isomerization rates at certain wavelengths, notably red-shifting the onset of photoisomerization. This effect is present under both strong and weak light-matter couplings. Second, kinetic competition between polariton localization into reactive molecular states and cavity losses leads to a suppression of the photoisomerization yield. Finally, our key result is that in reaction mixtures with multiple reactant isomers, exhibiting partially overlapping optical transitions and distinct isomerization pathways, the cavity resonance can be tuned to funnel photoexcitations into specific reactant isomers. Thus, upon decoherence, polaritons localize into a chosen isomer, selectively triggering the latter's photoisomerization despite initially being delocalized across all isomers. This result suggests that careful tuning of the cavity resonance is a promising avenue to steer chemical reactions and enhance product selectivity in reaction mixtures.

Baseline metabolic tumour burden improves risk stratification in Hodgkin lymphoma: A Children's Oncology Group study.

The Children's Oncology Group AHOD0831 study used a positron emission tomography (PET) response-adapted approach in high-risk Hodgkin lymphoma, whereby slow early responders (SERs) received more intensive therapy than rapid early responders (RERs). We explored if baseline PET-based characteristics would improve risk stratification. Of 166 patients enrolled in the COG AHOD0831 study, 94 (57%) had baseline PET scans evaluable for quantitative analysis. For these patients, total body metabolic tumour volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax ) and peak SUV (SUVpeak ) were obtained. MTV/TLG thresholds were an SUV of 2.5 (MTV2.5 /TLG2.5 ) and 40% of the tumour SUVmax (MTV40% /TLG40% ). TLG2.5 was associated with event-free survival (EFS) in the complete cohort (p = 0.04) and in RERs (p = 0.01), but not in SERs (p = 0.8). The Youden index cut-off for TLG2.5 was 1841. Four-year EFS was 92% for RER/TLG2.5  up to 1841, 60% for RER/TLG2.5  greater than 1841, 74% for SER/TLG2.5  up to 1841 and 79% for SER/TLG2.5  greater than 1841. Second EFS for RER/TLG2.5  up to 1841 was 100%. Thus, RERs with a low baseline TLG2.5 experienced excellent EFS with less intensive therapy, whereas RERs with a high baseline TLG2.5 experienced poor EFS. These findings suggest that patients with a high upfront tumour burden may benefit from intensified therapy, even if they achieve a RER.

Prognostic value of chest x-ray- and CT-defined large mediastinal adenopathy in high-risk pediatric Hodgkin lymphoma: A report from the Children's Oncology Group Study AHOD0831.

PURPOSE/OBJECTIVE: We compared the prognostic value of chest radiograph (CXR)- and computed tomography (CT)-derived definition of large mediastinal adenopathy (LMA) in pediatric Hodgkin lymphoma (HL). MATERIALS/METHODS: Total 143 patients treated for stage IIIB/IVB HL on COG AHOD0831 were included in this study. Six definitions of LMA were investigated: (i) mediastinal mass ratio on CXR (MRCXR ) > 1/3; (ii) mediastinal mass ratio on CT (MRCT ) > 1/3; (iii) mediastinal mass volume on CT (MVCT ) > 200 mL; (iv) normalized mediastinal mass volume (MVCT /thoracic diameter [TD]) > 1 mL/mm; (v) mediastinal mass diameter on CT (MDCT ) > 10 cm; and (vi) normalized mediastinal mass diameter (MDCT /TD) > 1/3. RESULTS: Median age at diagnosis was 15.8 years (range: 5.2-21.3 years). In patients with a slow early response (SER) to chemotherapy, MVCT  > 200 mL, MDCT  > 10 cm, and MDCT /TD > 1/3 were associated with worse relapse-free survival (RFS) on MVA, while MRCXR  > 1/3, MRCT  > 1/3, and MVCT /TD > 1 mL/mm trended toward worse RFS; MDCT /TD was the most strongly prognostic for inferior RFS, with a hazard ratio of 6.41 for MDCT /TD > 1/3 versus ≤1/3 on MVA (p = .02). CONCLUSION: LMA according to MVCT  > 200 mL, MDCT  > 10 cm, and MDCT /TD > 1/3 is associated with poor prognosis in advanced-stage HL patients with SER. The normalized mediastinal diameter, MDCT /TD > 1/3 appears to be the strongest predictor of inferior RFS.

Simultaneous Correlative Interferometer Technique for Direction Finding of Signal Sources.

In this paper, we propose a novel simultaneous Correlative Interferometer (CI) technique that elaborately estimates the Direction of Arrival (DOA) of multiple source signals incident on an antenna array. The basic idea of the proposed technique is that the antenna-array-based receiver compares the phase of the received signal with one of the candidates at each time sample and jointly exploits these multiple time samples to estimate the DOAs of multiple signal sources. The proposed simultaneous CI-based DOA estimation technique collectively utilizes multiple time-domain samples and can be regarded as a generalized version of the conventional CI algorithm for the case of multiple time-domain samples. We first thoroughly review the conventional CI algorithm to comprehensively explain the procedure of the direction-finding algorithm that adopts the phase information of received signals. We also discuss several technical issues of conventional CI-based DOA estimation techniques that are originally proposed for the case of a single time-domain sample. Then, we propose a simultaneous CI-based DOA estimation technique with multi-sample diversity as a novel solution for the case of multiple time-domain samples. We clearly compare the proposed simultaneous CI technique with the conventional CI technique and we compare the existing Multiple Signal Classification (MUSIC)-based DOA estimation technique with the conventional CI-based technique by using the DOA spectrum as well. To the best of our knowledge, the simultaneous CI-based DOA estimation technique that effectively utilizes the characteristics of multiple signal sources over multiple time-domain samples has not been reported in the literature. Through extensive computer simulations, we show that the proposed simultaneous CI technique significantly outperforms both the conventional CI technique in terms of DOA estimation even in harsh environments and with various antenna array structures. It is worth noting that the proposed simultaneous CI technique results in much better performance than the classical MUSIC algorithm, which is one of the most representative subspace-based DOA estimation techniques.

A microdose clinical trial to evaluate [18F]Florastamin as a positron emission tomography imaging agent in patients with prostate cancer.

PURPOSE: To evaluate the biodistribution of [18F]Florastamin, a novel 18F-labelled positron emission tomography (PET) tracer for prostate-specific membrane antigen (PSMA) for the diagnosis of prostate cancer. METHODS: PET was performed for five healthy controls and 10 patients with prostate cancer at 0, 10, 30, 70, and 120 mins after injecting 370 MBq of [18F]Florastamin. The maximum standardised uptake value (SUVmax) was evaluated in the primary tumour. The mean SUVmax (SUVmean) was evaluated in normal organs. Furthermore, the residence time was evaluated by assessing radioactivity in each organ. The internal radiation dosimetry was calculated using the OLINDA/EXM software. RESULTS: The SUVmax in primary tumours increased with time. A favourable tumour to background ratio was also observed over time. Multiple lymph nodes and bone metastases were also evaluated and showed a similar pattern to SUVmax in the primary tumour. In one patient, a tiny lymph node metastasis was identified using [18F]Florastamin PET, which was not observed using other modalities, and was histologically confirmed. The highest absorbed dose was observed in the kidney (0.062 ± 0.015 mGy/MBq), followed by the bladder (0.032 ± 0.013 mGy/MBq), liver (0.022 ± 0.006 mGy/MBq), and salivary gland (0.018 ± 0.006 mGy/MBq). The effective dose with a 370 MBq injection of [18F]Florastamin was 1.81 mSv. No adverse events related to [18F]Florastamin were reported. CONCLUSION: We identified a novel PSMA-targeted PET ligand, [18F]Florastamin, for imaging prostate cancer. [18F]Florastamin showed a high SUVmax and relatively high tumour to background ratio in both primary tumour and metastatic lesions, which suggests its high sensitivity to detect tumours without any adverse events. TRIAL REGISTRATION: KCT0003924 registered at https://cris.nih.go.kr/ .

Head-to-head comparison of 18 F-FP-CIT and 123 I-FP-CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study.

123 I-FP-CIT and 18 F-FP-CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head-to-head comparisons between 123 I-FP-CIT and 18 F-FP-CIT. Therefore, in this study, 123 I-FP-CIT SPECT/CT was compared with 18 F-FP-CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT. Visual analysis showed that the striatal uptake of both radiotracers was decreased in the PD group, whereas striatal uptake was intact in the ET group. The SBR between 123 I-FP-CIT SPECT/CT and 18 F-FP-CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on 18 F-FP-CIT PET/CT were higher than those on 123 I-FP-CIT SPECT/CT (2.19 ± .87 and 1.22 ± .49, respectively; p < .01). The PCRs in these two modalities were correlated with each other (r = .71, p < .01). The mean PCRs on 18 F-FP-CIT PET/CT were not significantly higher than those on 123 I-FP-CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both 123 I-FP-CIT and 18 F-FP-CIT was decreased in the PD group when compared with the ET controls. Visual analyses using both methods did not affect the diagnostic accuracy in this study. However, semiquantitative analysis indicated a better contrast of 18 F-FP-CIT PET/CT relative to 123 I-FP-CIT SPECT/CT.

Imaging of Myocardial Ischemia-Reperfusion Injury Using Sodium [18F]Fluoride Positron Emission Tomography/Computed Tomography in Rats and Humans.

Positron emission tomography (PET)/computed tomography (CT) using sodium [18F]fluoride (Na[18F]F) has been proven to be a promising hot-spot imaging modality for myocardial infarction (MI). We investigated Na[18F]F uptake in ischemia-reperfusion injury (IRI) of rats and humans. Sodium [18F]fluoride PET/CT was performed in Sprague-Dawley rats that had IRI surgery, and it readily demonstrated prominent Na[18F]F uptake in the infarct area post-IRI. Sodium [18F]fluoride uptake was matched with negative 2,3,5-triphenyl-2 H-tetrazolium chloride staining results, accompanied by myocardial apoptosis and associated with positive calcium staining results. Furthermore, area at risk was negative for Na[18F]F uptake. Cyclosporine A (CysA) treatment reduced standardized uptake value of 18F over the infarct area, and a significant decrease in infarct size was also observed by the CysA treatment. In humans, Na[18F]F PET/CT readily demonstrated increased Na[18F]F uptake in the 2 patients with MI post-percutaneous coronary intervention. In conclusion, this study sheds light on the potential utility of Na[18F]F PET/CT as a hot-spot imaging modality for myocardial IRI.

The value of SPECT/CT in localizing pain site and prediction of treatment response in patients with chronic low back pain.

In many circumstances, causing sites of low back pain (LBP) cannot be determined only by anatomical imaging. Combined functional and morphological imaging such as bone scan with single-photon emission computed tomography/computed tomography (SPECT/CT) may be helpful in identifying active lesions. The purpose of this study was to evaluate the usefulness of bone SPECT/CT in localizing the pain site and the treatment of chronic LBP. One hundred seventy-five patients suffering from chronic LBP who underwent SPECT/CT were included, retrospectively. All of the patients received multiple general treatments according to the symptoms, and some of them underwent additional target-specific treatment based on SPECT/CT. Numerical rating scale (NRS) pain score was used to assess the pain intensity. Of 175 patients, 127 showed good response to the given therapies, while the rest did not. Overall, 79.4% of patients with definite active lesions showed good response. Patients with mild active or no lesions on SPECT/CT had relatively lower response rate of 63.0%. Good response was observed by the treatment with the guidance of active lesions identified on SPECT/CT. SPECT/CT could be useful in identifying active lesions in patients with chronic LBP and guiding the clinicians to use adequate treatment.

Prognostic value of preoperative metabolic tumor volume measured by ¹8F-FDG PET/CT and MRI in patients with endometrial cancer.

OBJECTIVE: Tumor metabolic activity is a significant prognostic factor for endometrial cancer; however, there are few reports on the clinical importance of metabolic tumor volume (MTV) in patients with endometrial cancer. Therefore, we evaluated the prognostic value of preoperative MTV measured by (18)F-FDG PET/CT and MRI in a group of these patients. METHODS: We retrospectively reviewed patients with pathologically proven endometrial cancer who had undergone preoperative (18)F-FDG PET/CT and MRI scans. The prognostic significance of PET/CT parameters and other clinicopathological variables was evaluated. RESULTS: A total of 76 consecutive patients were included in the study. The median follow-up duration was 27 mo (range 3 to 96 mo) after surgery. MTV was correlated with FIGO stage and SUVmax. Age and FIGO stage were independent prognostic factors for recurrence in the multivariate analysis. In the subgroup analysis for 62 patients with endometrioid endometrial cancer, age (hazard ratio 1.098, P = 0.007, 95% confidence interval (CI) 1.026-1.175) and an MTV index of ≥ 876.4 (hazard ratio 5.795, P = 0.032, 95% CI 1.160-28.958) were determined to be independent prognostic factors of recurrence, and there was a statistically significant difference in progression-free survival (PFS) between patients in the high MTV and low MTV groups (log-rank test, P = 0.002). CONCLUSION: Preoperative MTV of the primary tumor was an independent prognostic factor for PFS and was significantly associated with recurrence in patients with endometrioid endometrial cancer. MTV is a promising tool for the prediction of outcome in patients with endometrioid endometrial cancer.

64 Cu-DOTA-Rituximab PET/CT of B-Cell Non-Hodgkin Lymphoma for Imaging the CD20 Expression.

ABSTRACT: 64 Cu-DOTA-rituximab PET/CT was performed on a 62-year-old and a 71-year-old men diagnosed with B-cell non-Hodgkin lymphoma. Compared with 18 F-FDG PET/CT, lesions could be detected more sensitively, and it was confirmed that there was no discernible 64 Cu-DOTA-rituximab uptake in the tumor other than lymphoma. 64 Cu-DOTA-rituximab PET/CT could be a powerful tool for the diagnosis and monitoring treatment response of lymphoma because of imaging the CD20 expression.

Ultrafast imaging of polariton propagation and interactions.

Semiconductor excitations can hybridize with cavity photons to form exciton-polaritons (EPs) with remarkable properties, including light-like energy flow combined with matter-like interactions. To fully harness these properties, EPs must retain ballistic, coherent transport despite matter-mediated interactions with lattice phonons. Here we develop a nonlinear momentum-resolved optical approach that directly images EPs in real space on femtosecond scales in a range of polaritonic architectures. We focus our analysis on EP propagation in layered halide perovskite microcavities. We reveal that EP-phonon interactions lead to a large renormalization of EP velocities at high excitonic fractions at room temperature. Despite these strong EP-phonon interactions, ballistic transport is maintained for up to half-exciton EPs, in agreement with quantum simulations of dynamic disorder shielding through light-matter hybridization. Above 50% excitonic character, rapid decoherence leads to diffusive transport. Our work provides a general framework to precisely balance EP coherence, velocity, and nonlinear interactions.

Comparison of the Effects of DOTA and NOTA Chelators on 64Cu-Cudotadipep and 64Cu-Cunotadipep for Prostate Cancer.

BACKGROUND: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as 64Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, 64Cu-cudotadipep and 64Cu-cunotadipep, on pharmacokinetics. METHODS: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells. To evaluate specific PSMA-expressing tumor-targeting efficiency, micro-positron emission tomography (mcroPET)/computed tomography (CT) and biodistribution analysis were performed using PSMA+ PC3-PIP and PSMA- PC3-flu tumor xenografts. RESULTS: The serum stability of DOTA- or NOTA-conjugated 64Cu-cudotadipep and 64Cu-cunotadipep was >97%. The Ki value of the NOTA derivative, cunotadipep, in the in vitro affinity binding analysis was higher (2.17 ± 0.25 nM) than that of the DOTA derivative, cudotadipep (6.75 ± 0.42 nM). The cunotadipep exhibited a higher cellular uptake (6.02 ± 0.05%/1 × 106 cells) compared with the cudotadipep (2.93 ± 0.06%/1 × 106 cells). In the biodistribution analysis and microPET/CT imaging, the 64Cu-labeled NOTA derivative, 64Cu-cunotadipep, demonstrated a greater tumor uptake and lower liver uptake than the DOTA derivative. CONCLUSIONS: This study indicates that the PSMA-targeted 64Cu-cunotadipep can be applied in clinical practice owing to its high diagnostic power for prostate cancer.

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

Using Spectator Ligands to Enhance Nanocrystal-to-Molecule Electron Transfer.

Semiconductor nanocrystals (NCs) have emerged as promising photocatalysts. However, NCs are often functionalized with complex ligand shells that contain not only charge acceptors but also other "spectator ligands" that control NC solubility and affinity for target reactants. Here, we show that spectator ligands are not passive observers of photoinduced charge transfer but rather play an active role in this process. We find the rate of electron transfer from quantum-confined PbS NCs to perylenediimide acceptors can be varied by over a factor of 4 simply by coordinating cinnamate ligands with distinct dipole moments to NC surfaces. Theoretical calculations indicate this rate variation stems from both ligand-induced changes in the free energy for charge transfer and electrostatic interactions that alter perylenediimide electron acceptor orientation on NC surfaces. Our work shows NC-to-molecule charge transfer can be fine-tuned through ligand shell design, giving researchers an additional handle for enhancing NC photocatalysis.

The Prediction of HER2-Targeted Treatment Response Using 64Cu-Tetra-Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report.

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status. 64Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64Cu-DOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.

Incidental 18F-Florapronol Uptake in Meningioma.

ABSTRACT: A 76-year-old woman underwent 18F-florapronol (18F-FC119S, an amyloid ß imaging PET agent) PET, owing to cognitive impairment. 18F-florapronol PET images revealed an incidental 18F-florapronol uptake in the right frontal lobe. A well-enhancing extra-axial mass in the right frontal lobe was observed on MRI scans, suggesting a meningioma. After excision of the tumor, the biopsy results confirmed it as a meningothelial meningioma.

A preliminary clinical trial to evaluate 64Cu-NOTA-Trastuzumab as a positron emission tomography imaging agent in patients with breast cancer.

BACKGROUND: The purpose of this study was to evaluate both the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer. METHODS: PET images at 1, 24, and 48 h after 296 MBq of 64Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors' and metastatic lesions' maximum standardized uptake value (SUVmax) was evaluated. The mean SUVmax (SUVmean) was evaluated in the other organs, including the blood pool, liver, kidney, muscle, spleen, bladder, and the lungs, as well as the bones. Moreover, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed based on feedback regarding adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration. RESULTS: 64Cu-NOTA-Trastuzumab PET images showed that the overall SUVmean values in each organ negatively correlated with time. The liver's average SUVmean values were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 h, 24 h, and 48 h after injection, respectively. The average SUVmean blood values were measured at 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 h, 24 h, and 48 h after injection, respectively. The SUVmax of HER2-positive tumors was relatively higher than HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 h after injection, respectively). Tumor-to-background ratios were higher in the HER2-positive tumors than in the HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq). CONCLUSIONS: 64Cu-NOTA-Trastuzumab showed a specific uptake at the HER2-expressing tumors, thus making it a feasible and safe monitoring tool of HER2 tumor status in patients with breast cancer. TRIAL REGISTRATION: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr.

Automated quantification of baseline imaging PET metrics on FDG PET/CT images of pediatric Hodgkin lymphoma patients.

PURPOSE: For pediatric lymphoma, quantitative FDG PET/CT imaging features such as metabolic tumor volume (MTV) are important for prognosis and risk stratification strategies. However, feature extraction is difficult and time-consuming in cases of high disease burden. The purpose of this study was to fully automate the measurement of PET imaging features in PET/CT images of pediatric lymphoma. METHODS: 18F-FDG PET/CT baseline images of 100 pediatric Hodgkin lymphoma patients were retrospectively analyzed. Two nuclear medicine physicians identified and segmented FDG avid disease using PET thresholding methods. Both PET and CT images were used as inputs to a three-dimensional patch-based, multi-resolution pathway convolutional neural network architecture, DeepMedic. The model was trained to replicate physician segmentations using an ensemble of three networks trained with 5-fold cross-validation. The maximum SUV (SUVmax), MTV, total lesion glycolysis (TLG), surface-area-to-volume ratio (SA/MTV), and a measure of disease spread (Dmaxpatient) were extracted from the model output. Pearson's correlation coefficient and relative percent differences were calculated between automated and physician-extracted features. RESULTS: Median Dice similarity coefficient of patient contours between automated and physician contours was 0.86 (IQR 0.78-0.91). Automated SUVmax values matched exactly the physician determined values in 81/100 cases, with Pearson's correlation coefficient (R) of 0.95. Automated MTV was strongly correlated with physician MTV (R = 0.88), though it was slightly underestimated with a median (IQR) relative difference of - 4.3% (- 10.0-5.7%). Agreement of TLG was excellent (R = 0.94), with median (IQR) relative difference of - 0.4% (- 5.2-7.0%). Median relative percent differences were 6.8% (R = 0.91; IQR 1.6-4.3%) for SA/MTV, and 4.5% (R = 0.51; IQR - 7.5-40.9%) for Dmaxpatient, which was the most difficult feature to quantify automatically. CONCLUSIONS: An automated method using an ensemble of multi-resolution pathway 3D CNNs was able to quantify PET imaging features of lymphoma on baseline FDG PET/CT images with excellent agreement to reference physician PET segmentation. Automated methods with faster throughput for PET quantitation, such as MTV and TLG, show promise in more accessible clinical and research applications.

Early response monitoring of neoadjuvant chemotherapy using [18F]FDG PET can predict the clinical outcome of extremity osteosarcoma.

BACKGROUND: To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. METHODS: A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). RESULTS: A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25-34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47-24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16-30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over - 39.8% or Δ%SUV02 over - 54.1% showed worse EFS rates than others (p < 0.05). CONCLUSIONS: PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.