Emerging role of vascular burden in AT(N) classification in individuals with Alzheimer's and concomitant cerebrovascular burdens.

OBJECTIVES: Alzheimer's disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimer's pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p<0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimer's pathological changes (A-T+, A-N+; p=0.002) and Alzheimer's pathological changes (p<0.001) categories. CONCLUSION: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system.

Estimation of an Image Biomarker for Distant Recurrence Prediction in NSCLC Using Proliferation-Related Genes.

This study aimed to identify a distant-recurrence image biomarker in NSCLC by investigating correlations between heterogeneity functional gene expression and fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) image features of NSCLC patients. RNA-sequencing data and 18F-FDG PET images of 53 patients with NSCLC (19 with distant recurrence and 34 without recurrence) from The Cancer Imaging Archive and The Cancer Genome Atlas Program databases were used in a combined analysis. Weighted correlation network analysis was performed to identify gene groups related to distant recurrence. Genes were selected for functions related to distant recurrence. In total, 47 image features were extracted from PET images as radiomics. The relationship between gene expression and image features was estimated using a hypergeometric distribution test with the Pearson correlation method. The distant recurrence prediction model was validated by a random forest (RF) algorithm using image texture features and related gene expression. In total, 37 gene modules were identified by gene-expression pattern with weighted gene co-expression network analysis. The gene modules with the highest significance were selected (p-value < 0.05). Nine genes with high protein-protein interaction and area under the curve (AUC) were identified as hub genes involved in the proliferation function, which plays an important role in distant recurrence of cancer. Four image features (GLRLM_SRHGE, GLRLM_HGRE, SUVmean, and GLZLM_GLNU) and six genes were identified to be correlated (p-value < 0.1). AUCs (accuracy: 0.59, AUC: 0.729) from the 47 image texture features and AUCs (accuracy: 0.767, AUC: 0.808) from hub genes were calculated using the RF algorithm. AUCs (accuracy: 0.783, AUC: 0.912) from the four image texture features and six correlated genes and AUCs (accuracy: 0.738, AUC: 0.779) from only the four image texture features were calculated using the RF algorithm. The four image texture features validated by heterogeneity group gene expression were found to be related to cancer heterogeneity. The identification of these image texture features demonstrated that advanced prediction of NSCLC distant recurrence is possible using the image biomarker.

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.

Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP.

The potential role of visceral adipose tissue (VAT) as a prognostic factor in patients with diffuse large B cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy was explored. Total adipose tissue and VAT were measured by analyzing positron emission tomography (PET)/computed tomography (CT) images obtained during the initial staging of patients with DLBCL. The VAT ratio was calculated as follows: VAT ratio = VAT area/total adipose tissue area. Body mass index (BMI), sex, and International Prognostic Index (IPI) were also incorporated as co-variates in the final model of multivariate Cox regression analysis for survival. A total of 156 patients with DLBCL, who were treated with frontline R-CHOP, were enrolled in our study. The median patient age was 61 years, and 81 patients were male (51.9 %). The median cycle of R-CHOP was six. The IPI risk group was a strong prognostic factor for progression-free survival (PFS) and overall survival (OS) (p < 0.001). Obese BMIs were an independent prognostic factor for PFS, but not for OS in multivariate analyses, compared to patients with normal BMIs (HR = 0.43, 95 % CI = 0.19-0.98, and p = 0.046 for PFS). A high VAT ratio (third tertile) was an independent adverse prognostic factor for PFS and OS in multivariate analyses (HR = 2.87 and 2.66, 95 % CI = 1.30-6.32 and 1.30-5.44, and p = 0.009 and 0.007 for PFS and OS, respectively). VAT ratio was an independent prognostic factor for patients with DLBCL treated with first-line R-CHOP; thus, additional large prospective studies are warranted.

Prognostic significance of interim PET/CT based on visual, SUV-based, and MTV-based assessment in the treatment of peripheral T-cell lymphoma.

BACKGROUNDS: The role of interim PET/CT in peripheral T-cell lymphoma (PTCL) is less identified compared to other subtype of lymphoma. This study prospectively investigated the prognostic accuracy of sequential interim PET/CT using visual and quantitative assessment to determine whether it provided prognostic information for the treatment of PTCL. METHODS: Sixty-three patients with newly diagnosed PTCL were enrolled, and 59 patients underwent interim PET/CT after three or four courses of induction treatment. The response of interim PET/CT was assessed by three parameters: the Deauville five-point scale (5-PS), ΔSUVmax, and ΔMTV2.5. RESULTS: Over a median follow up of 40.3 months, each assessment of interim PET/CT using the 5-PS, ΔSUVmax, and ΔMTV2.5 had predictive value for progression-free survival. To increase the predictive accuracy of interim PET/CT, we divided patients into three groups according to the sum of scores for three adverse responses based on the visual, SUV-based and MTV-based assessment: favorable, intermediate, and poor responder. The clinical outcome of patients in the favorable group was significantly superior to patients in the poor or intermediate group. CONCLUSION: Visual, quantitative SUV-based, and MTV-based assessment in interim PET/CT are valuable for early treatment response assessment in patients with PTCL, and the combined approach using the three parameters was more efficient in discriminating between patients with different survival outcomes compared with single-parameter assessment. TRIAL REGISTRATION: NCT01470066 .

Prediction of response to neoadjuvant chemotherapy in osteosarcoma using dual-phase (18)F-FDG PET/CT.

OBJECTIVES: We evaluated the ability of dual-phase (18)F-FDG PET/CT to predict the histological response after neoadjuvant chemotherapy (NAC) in osteosarcoma. METHODS: Thirty-one patients with osteosarcoma treated with NAC and surgery were prospectively enrolled. After injection of (18)F-FDG, both early (~60 min) and delayed (~150 min) PET were acquired before and after the completion of NAC. SUVmax, early/delayed SUVmax change (RImax), and early/delayed SUVmean change (RImean) of tumour were measured before (SUV1, RImax1, and RImean1) and after NAC (SUV2, RImax2, and RImean2). Then, we calculated the percentage changes between SUV1 and SUV2 (%SUV). RESULTS: Twelve patients (39%) exhibited good histological response after NAC. SUVmax, RImax, and RImean significantly decreased after NAC. Before NAC, only RImean1 predicted good histological response with the optimal criterion of < 10%, sensitivity of 92%, specificity of 57%, and accuracy of 71%. After NAC, %SUV, SUV2, and RImax2 predicted histological response. By using combined criterion of %SUV and RImax2 or SUV2 and RImean1 or SUV2 and RImax2, accuracies were 81%, 77%, and 77%, respectively. CONCLUSIONS: The histological response after NAC could be predicted by using RImean1 before the initiation of NAC in osteosarcoma. The combined use of SUV and RI values may provide a better prediction. KEY POINTS: • Pretreatment dual-phase FDG-PET was useful to predict histological response in osteosarcoma. • A combination of early and delayed PET may increase the predictive value. • Early/delayed SUV change of tumours significantly decreased after neoadjuvant chemotherapy.

Prognostic value of 18F-FDG uptake by regional lymph nodes on pretreatment PET/CT in patients with resectable colorectal cancer.

PURPOSE: We evaluated the ability of pretreatment (18)F-FDG uptake by regional lymph nodes to predict the survival of patients with resectable colorectal cancer. METHODS: The records of 78 patients with AJCC stage III colorectal cancer (pathologically confirmed node-positive disease without evidence of distant metastasis) treated with surgery and adjuvant chemotherapy were retrospectively reviewed. The maximum standardized uptake values of the primary tumor (SUVp) and regional lymph nodes (SUVn) were measured by pretreatment (18)F-FDG PET/CT. The ROC curve analyses and the Cox proportional hazard model were used to analyze whether SUVp, SUVn, and clinicopathologic parameters could predict disease-free survival. RESULTS: Although there were no significant differences between the median SUVp in the event group and that in the non-event group, the median SUVn was significantly higher in the event group (1.7) than in the non-event group (0.8, p = 0.023). Based on the ROC curve analysis, SUVn predicted the event for disease-free survival (AUC = 0.668, p = 0.02) with the optimal criterion, sensitivity, specificity, and accuracy of > 1.2, 71%, 63%, and 65%, respectively. However, SUVp did not predict disease-free survival (AUC = 0.570, p = 0.349). Univariate analysis revealed that SUVn (p = 0.011) and venous invasion (p = 0.016) were associated with disease-free survival, but pathologic N stage was not (p = 0.09). By multivariate analysis, only SUVn > 1.2 independently shortened the disease-free survival (relative risk, 2.97; 95% CI, 1.14-7.74, p = 0.026). CONCLUSION: SUVn before surgery may be a useful prognostic marker in patients with AJCC stage III colorectal cancer.

Early response monitoring to neoadjuvant chemotherapy in osteosarcoma using sequential ¹8F-FDG PET/CT and MRI.

PURPOSE: We evaluated the potential of sequential fluorine-18 fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET)/computed tomography (CT) and MRI (PET/MRI) after one cycle of neoadjuvant chemotherapy to predict a poor histologic response in osteosarcoma. METHODS: A prospective study was conducted on 30 patients with osteosarcoma treated with two cycles of neoadjuvant chemotherapy and surgery. All patients underwent PET/MRI before, after one cycle, and after the completion of neoadjuvant chemotherapy, respectively. Imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor volume based on magnetic resonance (MR) images (MRV)] and their % changes were calculated on each PET/MRI data set, and histological responses were evaluated on the postsurgical specimen. RESULTS: A total of 17 patients (57%) exhibited a poor histologic response after two cycles of chemotherapy. Unlike the little volumetric change in MRI, PET parameters significantly decreased after one and two cycles of chemotherapy, respectively. After one cycle of chemotherapy, SUVmax, MTV, and TLG predicted the poor responders. Among these parameters, either MTV ≥ 47 mL or TLG ≥ 190 g after one cycle of chemotherapy was significantly associated with a poor histologic response on multivariate logistic regression analysis (OR 8.98, p = 0.039). The sensitivity, specificity, and accuracy of these parameters were 71%, 85% and 77%; and 71%, 85% and 77 %, respectively. CONCLUSION: The histologic response to neoadjuvant chemotherapy in osteosarcoma can be predicted accurately by FDG PET after one course of chemotherapy. Among PET parameters, MTV and TLG were independent predictors of the histologic response.

The combination of FDG PET and dynamic contrast-enhanced MRI improves the prediction of disease-free survival in patients with advanced breast cancer after the first cycle of neoadjuvant chemotherapy.

PURPOSE: The aim of this study was to investigate the potential of FDG PET/CT and MRI in predicting disease-free survival (DFS) after neoadjuvant chemotherapy (NAC) and surgery in patients with advanced breast cancer. METHODS: The analysis included 54 women with advanced breast cancer. All patients received three cycles of NAC, underwent curative surgery, and then received three cycles of additional chemotherapy. Before and after the first cycle of NAC, all patients underwent sequential PET/CT and MRI. All patients were analysed using a diverse range of parameters. including maximal standardized uptake value (SUV), percent change in SUV (ΔSUV), initial slope of the enhancement curve (MRslope), apparent diffusion coefficient (ADC), tumour size, change in MRslope (ΔMRslope), change in ADC (ΔADC), change in tumour size (Δsize) and other clinicopathological parameters]. The relationships between covariates and DFS after surgery were analysed using the Kaplan-Meier method and the multivariate Cox proportional hazards model. Time-dependent receiver operating characteristic curves were used to determine the optimal cut-off values of imaging parameters for DFS. RESULTS: Of the 54 patients, 13 (24 %) experienced recurrence at a median follow-up of 38 months (range 25 - 45 months). Univariate and multivariate analyses showed that a lesser decline in SUV, a lesser decline in MRslope, a lesser increase in ADC, and ER negativity were significantly associated with a poorer DFS (P = 0.0006, ΔSUV threshold -41 %; P = 0.0016, ΔMRslope threshold -6 %; P = 0.011, ΔADC threshold 11 %; and P = 0.0086, ER status, respectively). Patients with a combination of ΔSUV >-41 % and ΔMRslope >-6 % showed a significantly higher recurrence rate (77.8 %) than the remaining of patients (13.3 %, P < 0.0001). CONCLUSION: Functional parameters of both FDG PET and MRI after the first cycle of NAC are useful for predicting DFS in patients with advanced breast cancer. This approach could lead to an improvement in patient care because ineffective NAC agents could be avoided and more aggressive therapy could be used in high-risk patients.

Automatic Quantitative Assessment for Diagnostic and Therapeutic Response in Rodent Myocardial Infarct Model.

The purpose of this study was to investigate the most appropriate methodological approach for the automatic measurement of rodent myocardial infarct polar map using histogram-based thresholding and unsupervised deep learning (DL)-based segmentation. A rat myocardial infarction model was induced by ligation of the left coronary artery. Positron emission tomography (PET) was performed 60 min after the administration of 18F-fluoro-deoxy-glucose (18F-FDG), and PET was performed after injecting 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone). Single photon emission computed tomography was performed 60 min after injection of 99mTc-hexakis-2-methoxyisobutylisonitrile and 201Tl. Delayed contrast-enhanced magnetic resonance imaging was performed after injecting Gd-DTPA-BMA. Three types of thresholding methods (naive thresholding, Otsu's algorithm, and multi-Gaussian mixture model (MGMM)) were used. DL segmentation methods were based on a convolution neural network and trained with constraints on feature similarity and spatial continuity of the response map extracted from images by the network. The relative infarct sizes measured by histology and estimated R2 for 18F-FDG were 0.8477, 0.7084, 0.8353, and 0.9024 for naïve thresholding, Otsu's algorithm, MGMM, and DL segmentation, respectively. DL-based method improved the accuracy of MI size assessment.

¹8F-FDG PET SUVmax as an indicator of histopathologic response after neoadjuvant chemotherapy in extremity osteosarcoma.

PURPOSE: This study evaluated the usefulness of the maximum standardized uptake value (SUVmax) as a measure of histologic response to neoadjuvant chemotherapy in patients with extremity osteosarcoma. The correlation between [(18) F]FDG PET SUVmax values and histologic response to preoperative chemotherapy was also assessed prospectively using PET/MRI. METHODS: A total of 26 consecutive patients with high-grade osteosarcoma were prospectively enrolled. All patients underwent parallel PET and MRI scans before and after neoadjuvant chemotherapy. Using the PET and MRI images and pathologic mapping, we assessed the percentage necrosis by histology at the highest metabolic activity point in the tumors. This was defined as the minimum histologic response. The predictive values of SUVmax before (SUV1) and after (SUV2) chemotherapy and the SUV change ratio were determined. Correlations were also investigated among SUV2, minimum histologic response and histologic response. RESULTS: Histologically, 13 patients were classified as good responders and 13 as poor responders. Patients with an SUV2 of >5 showed a poor histologic response. A significant correlation was found between SUV2 and histologic response (Spearman's rho -0.642; P < 0.001), and SUV2 and histologic response were both found to be significantly correlated with minimum histologic response (Spearman's rho -0.515 and 0.911; P = 0.007 and P < 0.001, respectively). CONCLUSION: A SUVmax of more than 5 after neoadjuvant chemotherapy identified the majority of histologic nonresponders (sensitivity 61.3 %, PPV 88.9 %). Tumor necrosis at the point of maximum metabolic activity was found to be significantly correlated with the histologic response of entire resected specimen.

Interim PET/CT-based prognostic model for the treatment of diffuse large B cell lymphoma in the post-rituximab era.

The prognostic accuracy of interim (18)F-fluoro-2-dexoy-D-glucose positron emission tomography/computerized tomography (PET/CT) using three different methods of response assessments during rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy was investigated in 186 patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The response of interim PET/CT was assessed based on a combined evaluation of the Deauville five-point scale (5-PS), the rates of reduction in the maximal standardized uptake value (ΔSUVmax), and the rates of reduction in the metabolic tumor volume (ΔMTV2.5). Positivity on the 5-PS, the optimal cutoff of ΔSUVmax, or the optimal cutoff of ΔMTV2.5 could each predict disease progression. Over a median follow-up of 22.8 months, the assessment of responses based on the 5-PS, ΔSUVmax, and ΔMTV2.5 had prognostic value for progression-free survival. When patients were allocated a score of 0 to 3 depending on the presence of an inadequate response by visual, ΔSUVmax, or ΔMTV2.5, the outcomes of patients with a score of 0 were significantly superior to those with a score of 1, 2, or 3. The interim PET/CT response based on visual, SUV-based, and MTV-based assessment had significant negative predictive value for disease progression and a high potential for predicting outcomes of patients with DLBCL.

Comparison of (18)F-FDG PET/CT and (99 m)Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma.

OBJECTIVE: We compared the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and (99 m)Tc-methylene diphosphonate bone scintigraphy (BS) for the detection of bone metastasis in osteosarcoma. MATERIALS AND METHODS: We retrospectively reviewed 206 patients with stage II-IV osteosarcoma treated with surgery and chemotherapy as well as at least one paired PET/CT and BS scan (defined as an examination). PET/CT and BS images were interpreted separately. When analyzing the diagnostic yield of a combination of PET/CT and BS (PET/CT+BS), an examination was considered positive if either PET/CT or BS scored positive. The final diagnosis was obtained from histological findings or clinical follow-up with imaging studies for at least 6 months. Diagnostic performances of PET/CT, BS, and their combinations were calculated. RESULTS: Out of 833 examinations in 206 patients, 55 with 101 lesions in 38 patients were confirmed as bone metastases. The sensitivity, specificity, and diagnostic accuracy were 95, 98, and 98%, respectively, for PET/CT; 76, 97, and 96%, respectively, for BS; and 100, 96, and 97%, respectively, for PET/CT+BS in an examination-based analysis. Lesion-based analysis demonstrated that the sensitivity of PET/CT+BS (100%) was significantly higher than that of PET/CT (92%) or BS (74%) alone. BS detected significantly less bone metastases in the growth plate region than outside the growth plate region (22 vs. 77%). CONCLUSIONS: PET/CT is more sensitive and accurate than BS for diagnosing bone metastases in osteosarcoma. The combined use of PET/CT and BS improves sensitivity.

Deep Learning-Based Delayed PET Image Synthesis from Corresponding Early Scanned PET for Dosimetry Uptake Estimation.

The acquisition of in vivo radiopharmaceutical distribution through imaging is time-consuming due to dosimetry, which requires the subject to be scanned at several time points post-injection. This study aimed to generate delayed positron emission tomography images from early images using a deep-learning-based image generation model to mitigate the time cost and inconvenience. Eighteen healthy participants were recruited and injected with [18F]Fluorodeoxyglucose. A paired image-to-image translation model, based on a generative adversarial network (GAN), was used as the generation model. The standardized uptake value (SUV) mean of the generated image of each organ was compared with that of the ground-truth. The least square GAN and perceptual loss combinations displayed the best performance. As the uptake time of the early image became closer to that of the ground-truth image, the translation performance improved. The SUV mean values of the nominated organs were estimated reasonably accurately for the muscle, heart, liver, and spleen. The results demonstrate that the image-to-image translation deep learning model is applicable for the generation of a functional image from another functional image acquired from normal subjects, including predictions of organ-wise activity for specific normal organs.

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.

The role of 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma after radioimmunotherapy using 131I-rituximab as consolidation therapy.

PURPOSE: To evaluate the prognostic value of pretreatment 18F-FDG PET/CT after consolidation therapy of 131I-rituximab in patients with diffuse large B-cell lymphoma (DLBCL) who had acquired complete remission after receiving chemotherapy. METHODS: Patients who were diagnosed with DLBCL via histologic confirmation were retrospectively reviewed. All patients had achieved complete remission after 6 to 8 cycles of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) chemotherapy after which they underwent consolidation treatment with 131I-rituximab. 18F-FDG PET/CT scans were performed before R-CHOP for initial staging. The largest diameter of tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment 18F-FDG PET/CT scans. Receiver-operating characteristic curves analysis was introduced for assessing the optimal criteria. Kaplan-Meier curve survival analysis was performed to evaluate both relapse free survival (RFS) and overall survival (OS). RESULTS: A total of 15 patients (12 males and 3 females) with a mean age of 56 (range, 30-73) years were enrolled. The median follow-up period of these patients was 73 months (range, 11-108 months). Four (27%) patients relapsed. Of them, three died during follow-up. Median values of the largest tumor size, highest SUVmax, MTV, and TLG were 5.3 cm (range, 2.0-16.4 cm), 20.2 (range, 11.1-67.4), 231.51 (range, 15-38.34), and 1277.95 (range, 238.37-10341.04), respectively. Patients with SUVmax less than or equal to 16.9 showed significantly worse RFS than patients with SUVmax greater than 16.9 (5-year RFS rate: 60% vs. 100%, p = 0.008). Patients with SUVmax less than or equal to 16.9 showed significantly worse OS than patients with SUVmax greater than 16.9 (5-year OS rate: 80% vs. 100% p = 0.042). CONCLUSION: Higher SUVmax at pretreatment 18F-FDG PET/CT was associated with better relapse free survival and overall survival in DLBCL patients after consolidation therapy with 131I-rituximab. However, because this study has a small number of patients, a phase 3 study with a larger number of patients is needed for clinical application in the future.

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.

Comparison of ¹³¹I whole-body imaging, ¹³¹I SPECT/CT, and ¹8F-FDG PET/CT in the detection of metastatic thyroid cancer.

PURPOSE: The aim of this study was to compare (131)I whole-body scintigraphy (WBS), WBS with (131)I single photon emission computed tomography/computed tomography (SPECT/CT), and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the detection of distant metastases of differentiated thyroid cancer (DTC). METHODS: A total of 140 patients with 258 foci of suspected distant metastases were evaluated. (131)I WBS, (131)I SPECT/CT, and (18)F-FDG PET/CT images were interpreted separately. The final diagnosis was obtained from histopathologic study, serum thyroglobulin level, other imaging modalities, and/or clinical follow-up. RESULTS: Of the 140 patients with 258 foci, 46 patients with 166 foci were diagnosed as positive for distant metastasis. The sensitivity, specificity, and diagnostic accuracy of each imaging modality were 65, 55, and 59%, respectively, for (131)I WBS; 65, 95, and 85% for (131)I SPECT/CT, respectively; and 61, 98, and 86%, respectively, for (18)F-FDG PET/CT in patient-based analyses. Lesion-based analyses demonstrated that both SPECT/CT and PET/CT were superior to WBS (p<0.001) in all patient groups. SPECT/CT was superior to WBS and PET/CT (p<0.001) in patients who received a single challenge of radioiodine therapy, whereas PET/CT was superior to WBS (p=0.005) and SPECT/CT (p=0.013) in patients who received multiple challenges. CONCLUSION: Both SPECT/CT and PET/CT demonstrated high diagnostic performance in detecting metastatic thyroid cancer. SPECT/CT was highly accurate in patients who underwent a single challenge of radioiodine therapy. In contrast, (18)F-FDG PET/CT presented the highest diagnostic performance in patients who underwent multiple challenges of radioiodine therapy.