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1.
Artigo em Inglês | MEDLINE | ID: mdl-38696130

RESUMO

PURPOSE: To improve reproducibility and predictive performance of PET radiomic features in multicentric studies by cycle-consistent generative adversarial network (GAN) harmonization approaches. METHODS: GAN-harmonization was developed to harmonize whole-body PET scans to perform image style and texture translation between different centers and scanners. GAN-harmonization was evaluated by application to two retrospectively collected open datasets and different tasks. First, GAN-harmonization was performed on a dual-center lung cancer cohort (127 female, 138 male) where the reproducibility of radiomic features in healthy liver tissue was evaluated. Second, GAN-harmonization was applied to a head and neck cancer cohort (43 female, 154 male) acquired from three centers. Here, the clinical impact of GAN-harmonization was analyzed by predicting the development of distant metastases using a logistic regression model incorporating first-order statistics and texture features from baseline 18F-FDG PET before and after harmonization. RESULTS: Image quality remained high (structural similarity: left kidney ≥ 0.800, right kidney ≥ 0.806, liver ≥ 0.780, lung ≥ 0.838, spleen ≥ 0.793, whole-body ≥ 0.832) after image harmonization across all utilized datasets. Using GAN-harmonization, inter-site reproducibility of radiomic features in healthy liver tissue increased at least by ≥ 5 ± 14% (first-order), ≥ 16 ± 7% (GLCM), ≥ 19 ± 5% (GLRLM), ≥ 16 ± 8% (GLSZM), ≥ 17 ± 6% (GLDM), and ≥ 23 ± 14% (NGTDM). In the head and neck cancer cohort, the outcome prediction improved from AUC 0.68 (95% CI 0.66-0.71) to AUC 0.73 (0.71-0.75) by application of GAN-harmonization. CONCLUSIONS: GANs are capable of performing image harmonization and increase reproducibility and predictive performance of radiomic features derived from different centers and scanners.

2.
Lancet Digit Health ; 6(4): e251-e260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519153

RESUMO

BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Inteligência Artificial , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos , Estudos Retrospectivos
3.
Eur J Radiol ; 170: 111198, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992608

RESUMO

PURPOSE: The purpose of this study was to assess the ability of pretreatment PET parameters and peripheral blood biomarkers to predict progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with ICIT. METHODS: We prospectively included 87 patients in this study who underwent pre-treatment [18F]-FDG PET/CT. Organ-specific and total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using a semiautomatic software. Sites of organ involvement (SOI) were assessed by PET/CT. The log-rank test and Cox-regression analysis were used to assess associations between clinical, laboratory, and imaging parameters with PFS and OS. Time dependent ROC were calculated and model performance was evaluated in terms of its clinical utility. RESULTS: MTV increased with the number of SOI and was correlated with neutrophil and lymphocyte cell count (Spearman's rho = 0.27 or 0.32; p =.02 or 0.003; respectively). Even after adjustment for known risk factors, such as PD-1 expression and neutrophil cell count, the MTV and the number of SOI were independent risk factors for progression (per 100 cm3; adjusted hazard ratio [aHR]: 1.13; 95% confidence interval [95%CI]: 1.01-1.28; p =.04; single SOI vs. ≥ 4 SOI: aHR: 2.26, 95%CI: 1.04-4.94; p =.04). MTV and the number of SOI were independent risk factors for overall survival (per 100 cm3 aHR: 1.11, 95%CI: 1.01-1.23; p =.03; single SOI vs. ≥ 4 SOI: aHR: 4.54, 95%CI: 1.64-12.58; p =.04). The combination of MTV and the number of SOI improved the risk stratification for PFS and OS (log-rank test p <.001; C-index: 0.64 and 0.67). CONCLUSION: The MTV and the number of SOI are simple imaging markers that provide complementary information to facilitate risk stratification in NSCLC patients scheduled for ICIT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Inibidores de Checkpoint Imunológico , Carga Tumoral , Fluordesoxiglucose F18/metabolismo , Prognóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Estudos Retrospectivos , Glicólise , Compostos Radiofarmacêuticos
4.
Int J Mol Sci ; 24(18)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37761975

RESUMO

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

5.
Radiology ; 307(4): e222010, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37070991

RESUMO

Background Prostate-specific membrane antigen (PSMA) PET has high specificity in localizing primary tumors and metastases in patients with prostate cancer, but the individual overall survival probability is still difficult to estimate. Purpose To develop a prognostic risk score using PSMA PET-derived organ-specific total tumor volumes for predicting overall survival in patients with prostate cancer. Materials and Methods Men with prostate cancer who underwent PSMA PET/CT from January 2014 to December 2018 were evaluated retrospectively. All patients from center A were split into training (80%) and internal validation (20%) cohorts. Randomly selected patients from center B were used for external validation. Organ-specific tumor volumes were automatically quantified from PSMA PET scans by a neural network. A prognostic score was selected using multivariable Cox regression guided by the Akaike information criterion (AIC). The final prognostic risk score fitted on the training set was applied to both validation cohorts. Results A total of 1348 men (mean age, 70 years ± 8 [SD]) were included, with 918 patients in the training cohort, 230 in the internal validation cohort, and 200 in the external validation cohort. The median follow-up time was 55.7 months (IQR, 46.7-65.1 months; >4 years; 429 deaths occurred). A body weight-adjusted prognostic risk score integrating total, bone, and visceral tumor volumes obtained high C index values in the internal (0.82) and external (0.74) validation cohorts, as well as in patients with castration-resistant (0.75) and hormone-sensitive (0.68) disease. The fit of the statistical model for the prognostic score was improved compared with a model containing total tumor volume only (AIC, 3324 vs 3351; likelihood ratio test, P < .001). Calibration plots ascertained good model fit. Conclusion The newly developed risk score that included prostate-specific membrane antigen PET-derived organ-specific tumor volumes had good model fit for predicting overall survival in both internal and external validation cohorts. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Civelek in this issue.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Masculino , Humanos , Idoso , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Carga Tumoral , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Fatores de Risco , Radioisótopos de Gálio
6.
Eur J Radiol ; 161: 110732, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36804313

RESUMO

The introduction of neoadjuvant immune checkpoint inhibitors plus platinum-based chemotherapy has changed treatment regimens of patient's early-stage lung cancer. This treatment combination induces high rates of complete pathologic response and improves clinical endpoints. Imaging plays a fundamental role in assessment of treatment response, monitoring of (immune-related) adverse events and enables both the surgeon and pathologist optimal treatment and diagnostic workup of the resected tumor samples. Knowledge of the strengths and weaknesses of diagnostic imaging in this setting are essential for radiologists to provide valuable input in multidisciplinary team decisions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Neoadjuvante/métodos , Imunoterapia/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Radiologistas
7.
Eur J Nucl Med Mol Imaging ; 50(2): 546-558, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36161512

RESUMO

PURPOSE: Head and neck squamous cell carcinomas (HNSCCs) are a molecularly, histologically, and clinically heterogeneous set of tumors originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. This heterogeneous nature of HNSCC is one of the main contributing factors to the lack of prognostic markers for personalized treatment. The aim of this study was to develop and identify multi-omics markers capable of improved risk stratification in this highly heterogeneous patient population. METHODS: In this retrospective study, we approached this issue by establishing radiogenomics markers to identify high-risk individuals in a cohort of 127 HNSCC patients. Hybrid in vivo imaging and whole-exome sequencing were employed to identify quantitative imaging markers as well as genetic markers on pathway-level prognostic in HNSCC. We investigated the deductibility of the prognostic genetic markers using anatomical and metabolic imaging using positron emission tomography combined with computed tomography. Moreover, we used statistical and machine learning modeling to investigate whether a multi-omics approach can be used to derive prognostic markers for HNSCC. RESULTS: Radiogenomic analysis revealed a significant influence of genetic pathway alterations on imaging markers. A highly prognostic radiogenomic marker based on cellular senescence was identified. Furthermore, the radiogenomic biomarkers designed in this study vastly outperformed the prognostic value of markers derived from genetics and imaging alone. CONCLUSION: Using the identified markers, a clinically meaningful stratification of patients is possible, guiding the identification of high-risk patients and potentially aiding in the development of effective targeted therapies.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Marcadores Genéticos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/genética , Prognóstico , Medição de Risco
8.
Biomedicines ; 10(12)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36551858

RESUMO

Therapy options for advanced pancreatic neuroendocrine tumors (pNETs) include the mTOR inhibitor everolimus and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE, however further optimization in the therapeutic landscape is required as response rates are still low. In this study, we investigated the synergistic and potentially enhanced efficacy of a combined treatment with everolimus and [177Lu]Lu-DOTA-TATE in a mouse model. Baseline [68Ga]Ga-DOTA-TATE PET scans were obtained five days after athymic CD1 mice were inoculated with AR42J tumor cells, before separating the animals into four groups. Group 1 received a placebo, group 2 everolimus, group 3 a placebo and PRRT, and group 4 everolimus and PRRT. The treatment response was monitored by manually measuring the tumor volumes (manual tumor volume, MTV) and conducting sequential [68Ga]Ga-DOTA-TATE PET scans at one, two, and four weeks after treatment induction. The biological tumor volume (BTV) was derived from PET scans using threshold-based volume of interest (VOI) measurements. Tracer uptake was measured semi-quantitatively as a tumor to background ratio (TBR). Mice were euthanized due to excessive tumor growth according to the ethics protocol; blood samples were drawn for the preparation of full blood counts and kidneys were obtained for histological analysis. For the histological assessment, a standardized score (renal damage score, RDS) was used. Full blood counts showed significantly increased numbers of neutrophils and lymphocytes in the groups receiving PRRT. All other parameters did not differ relevantly. In the histological analysis, groups receiving PRRT had a significantly higher RDS, whereas everolimus only tended to cause an increase in the RDS. Mice in groups 1 and 2 had to be euthanized due to excessive tumor growth two weeks after the start of the therapy, whereas follow-up in groups 3 and 4 comprised four weeks. PRRT significantly inhibited tumor growth; the administration of everolimus did not induce an additional effect. A good correlation existed between MTV and BTV. PRRT significantly reduced the TBR. [68Ga]Ga-DOTA-TATE PET is suitable for monitoring tumor growth in the applied model. The high efficacy of [177Lu]Lu-DOTA-TATE is not enhanced by the combination with everolimus.

9.
Front Endocrinol (Lausanne) ; 13: 962090, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246898

RESUMO

Introduction: Obesity affects a rising proportion of the population and is an important risk factor for unfavorable outcomes in viral disease including severe acute respiratory syndrome coronavirus 2- associated diseases. Torque Teno virus (TTV) is a ubiquitous and apathogenic virus which reflects the immune function of its host. The aim of this study was to investigate the association between obesity and TTV load - an indirect marker of compromised viral immune response. Methods: TTV was quantified by TTV R-GENE® PCR in a total of 89 participants of which 30 were lean (BMI <25 kg/m2) and 59 were obese (BMI >30 kg/m2). For 38 subjects, follow-up was available after bariatric surgery. Results: TTV load was higher in individuals with obesity (median 2.39, IQR: 1.69-3.33 vs. 1.88, IQR 1.08-2.43 log10 copies/mL; p = 0.027). Multivariable linear modeling revealed an independent association between TTV load and obesity. TTV was positively correlated with waist-to-hip ratio and inversely with 25OH vitamin D levels. Interleukin 6 and fasting insulin resistance were confounders of the association between TTV and obesity, while age was an effect modifier. TTV load increased by 87% (95% CI 2-243%) in the year following bariatric surgery. Discussion: A higher TTV load in obese individuals may reflect compromised immune function and thus might serve for risk stratification of unfavorable outcomes during infectious disease, including coronavirus disease 2019, in this population. Our data warrant further analysis of TTV-based risk assessment in obese individuals in the context of infectious disease-associated outcomes.


Assuntos
COVID-19 , Infecções por Vírus de DNA , Torque teno virus , Infecções por Vírus de DNA/complicações , Infecções por Vírus de DNA/epidemiologia , Humanos , Interleucina-6 , Obesidade , Magreza , Vitamina D
10.
Front Oncol ; 12: 1017911, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303841

RESUMO

Background: This study proposes machine learning-driven data preparation (MLDP) for optimal data preparation (DP) prior to building prediction models for cancer cohorts. Methods: A collection of well-established DP methods were incorporated for building the DP pipelines for various clinical cohorts prior to machine learning. Evolutionary algorithm principles combined with hyperparameter optimization were employed to iteratively select the best fitting subset of data preparation algorithms for the given dataset. The proposed method was validated for glioma and prostate single center cohorts by 100-fold Monte Carlo (MC) cross-validation scheme with 80-20% training-validation split ratio. In addition, a dual-center diffuse large B-cell lymphoma (DLBCL) cohort was utilized with Center 1 as training and Center 2 as independent validation datasets to predict cohort-specific clinical endpoints. Five machine learning (ML) classifiers were employed for building prediction models across all analyzed cohorts. Predictive performance was estimated by confusion matrix analytics over the validation sets of each cohort. The performance of each model with and without MLDP, as well as with manually-defined DP were compared in each of the four cohorts. Results: Sixteen of twenty established predictive models demonstrated area under the receiver operator characteristics curve (AUC) performance increase utilizing the MLDP. The MLDP resulted in the highest performance increase for random forest (RF) (+0.16 AUC) and support vector machine (SVM) (+0.13 AUC) model schemes for predicting 36-months survival in the glioma cohort. Single center cohorts resulted in complex (6-7 DP steps) DP pipelines, with a high occurrence of outlier detection, feature selection and synthetic majority oversampling technique (SMOTE). In contrast, the optimal DP pipeline for the dual-center DLBCL cohort only included outlier detection and SMOTE DP steps. Conclusions: This study demonstrates that data preparation prior to ML prediction model building in cancer cohorts shall be ML-driven itself, yielding optimal prediction models in both single and multi-centric settings.

11.
Eur J Nucl Med Mol Imaging ; 50(1): 205-217, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36063201

RESUMO

PURPOSE: The purpose of this study was to determine whether multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) can improve locoregional staging of rectal cancer (RC) and to assess its prognostic value after resection. METHODS: In this retrospective study, 46 patients with primary RC, who underwent multiparametric 18F-fluorodeoxyglucose (FDG) PET/MRI, followed by surgical resection without chemoradiotherapy, were included. Two readers reviewed T- and N- stage, mesorectal involvement, sphincter infiltration, tumor length, and distance from anal verge. In addition, diffusion-weighted imaging (DWI) and PET parameters were extracted from the multiparametric protocol and were compared to radiological staging as well as to the histopathological reference standard. Clinical and imaging follow-up was systematically assessed for tumor recurrence and death. RESULTS: Locally advanced rectal cancers (LARC) exhibited significantly higher metabolic tumor volume (MTV, AUC 0.74 [95% CI 0.59-0.89], p = 0.004) and total lesion glycolysis (TLG, AUC 0.70 [95% CI 0.53-0.87], p = 0.022) compared to early tumors. T-stage was associated with MTV (AUC 0.70 [95% CI 0.54-0.85], p = 0.021), while N-stage was better assessed using anatomical MRI sequences (AUC 0.72 [95% CI 0.539-0.894], p = 0.032). In the multivariate regression analysis, depending on the model, both anatomical MRI sequences and MTV/TLG were capable of detecting LARC. Combining anatomical MRI stage and MTV/TLG led to a superior diagnostic performance for detecting LARC (AUC 0.81, [95% CI 0.68-0.94], p < 0.001). In the survival analysis, MTV was independently associated with overall survival (HR 1.05 [95% CI 1.01-1.10], p = 0.044). CONCLUSION: Multiparametric PET-MRI can improve identification of locally advanced tumors and, hence, help in treatment stratification. It provides additional information on RC tumor biology and may have prognostic value.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Retais , Humanos , Fluordesoxiglucose F18/metabolismo , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Carga Tumoral , Prognóstico , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Estadiamento de Neoplasias
12.
Nucl Med Commun ; 43(11): 1113-1120, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36120814

RESUMO

OBJECTIVE: [ 177 Lu]Lu-PSMA radioligand therapy (PSMA-RLT) is a promising therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) and offers a survival benefit particularly to patients with only lymph node metastases. We therefore sought to evaluate the clinical outcome of this therapy in such a cohort. METHODS: Of all prostate cancer patients admitted to our department between September 2015 and March 2019 to receive 1-4 courses of PSMA-RLT (each course consisted of three cycles of highly standardized PSMA-RLT every 4 weeks), only 10 consecutive men were found to have nodal metastases only and were analyzed retrospectively. RESULTS: Nine out of 10 patients responded to their first PSMA-RLT course with a mean prostate-specific antigen (PSA) decline of 71.8 ± 25.2%, seven of them demonstrated a PSA decline of ≥50%. Collectively, seven of eight patients responded to further PSMA-RLT courses with a total PSA reduction of 59.8 ± 30.0%, five of which showed a PSA reduction of ≥50%. One patient experienced complete remission. Median progression-free survival was 85 weeks (range 14-255 weeks) and median overall survival was not reached during the median observation time of 209 weeks (30-298 weeks). Univariate Cox-regression identified initial PSA decline as the only predictive parameter for progression-free survival ( P = 0.047). CONCLUSION: mCRPC patients with only lymph node metastases showed favorable survival and excellent response to PSMA-RLT, leading to transient partial remission of the disease in most of them.


Assuntos
Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio/uso terapêutico , Metástase Linfática , Masculino , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos , Estudos Retrospectivos
13.
Cancers (Basel) ; 14(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35954432

RESUMO

With the progressive aging of the population in industrially developed countries, as well as advances in diagnostic and biopsy techniques and improvements in patient awareness, the incidence of prostate cancer (PCa) is continuously increasing worldwide. Therefore, PCa is currently considered as the second leading cause of tumor-related death. Early detection of the tumor and its metastasis is essential, as the rate of disease recurrence is high and occurs in 27% to 53% of all patients who underwent curative therapy with radical prostatectomy or local radiotherapy. In this regard, the prostate specific membrane antigens, abbreviated as PSMAs, are type II membrane proteins that are highly expressed on the surface of malignant prostate tissue in PCa, particularly in aggressive, androgen-deprived, metastatic, and hormone-refractory PCa, and they are inversely associated with the androgen level. Up to 95% of adenocarcinomas of the prostate express PSMA receptors on their surface. Today, radionuclides that bind to these PSMA peptides are widely accepted for diagnostic and therapeutic purposes to specifically image and target prostate tumor cells at the molecular level, a process referred to as targeted theranostics. Numerous studies have demonstrated that the integration of these peptides into diagnostic and therapeutic procedures plays a critical role in the primary staging and treatment decisions of especially high-risk PCa, expands therapeutic options for patients with advanced stage of prostate tumor, and prolongs patients' survival rate. In this review article, we intend to briefly spotlight the latest clinical utilization of the PSMA-targeted radioligand PET imaging modality in patients with different stages of PCa. Furthermore, limitations and pitfalls of this diagnostic technique are presented.

14.
Curr Oncol ; 28(5): 3692-3704, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34590608

RESUMO

BACKGROUND: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [68Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran's Q test were applied to assess organ toxicity. RESULTS: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly (p < 0.05). CONCLUSION: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Idoso , Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Humanos , Rim/diagnóstico por imagem , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Glândulas Salivares/diagnóstico por imagem
15.
Cancers (Basel) ; 13(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065303

RESUMO

BACKGROUND: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. METHODS: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87-1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan-Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. RESULTS: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6-1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01-5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. CONCLUSION: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

16.
Mol Cell Endocrinol ; 534: 111365, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34126190

RESUMO

INTRODUCTION: Brown adipose tissue (BAT) is suggested to exhibit a sexual dimorphism and thus contributes to the observed sex differences in cardiometabolic risk observed between women and men. Clinical data supporting this hypothesis are however scarce. The aim of this study was to investigate the relationship between BAT activity and sex using positron emission tomography (PET) - the current gold-standard for BAT quantification. METHODS: In this study, we included 95 subjects with a wide BMI range (20-55 kg/m2) aged from 18 to 50 years. Avoiding shivering, participants were cooled with a water-perfused vest to achieve adequate BAT activation. BAT activity was determined by 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT). Cold-induced thermogenesis (CIT) was quantified by indirect calorimetry. RESULTS: BAT was present in 44.6% of pre-menopausal women and in 35.9% of men (p = 0.394). CIT was significantly higher in women (p = 0.024). Estradiol levels were positively associated with CIT independent of age, sex, body fat and other sex hormones (b = 0.360, p = 0.016). In women, CIT decreased during the menstrual cycle, with lower levels in the luteal phase similar to median concentrations in men. CONCLUSION: The prevalence of cold-activated BAT is slightly but non-significantly higher in pre-menopausal women than men. CIT is increased in females and independently associated with estradiol, suggesting that sex hormones may play a role in different thermogenic responses between men and women.


Assuntos
Tecido Adiposo Marrom/diagnóstico por imagem , Estradiol/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Termogênese , Tecido Adiposo Marrom/metabolismo , Adulto , Calorimetria Indireta , Temperatura Baixa , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Fase Luteal/metabolismo , Masculino , Pessoa de Meia-Idade , Pré-Menopausa/metabolismo , Caracteres Sexuais , Adulto Jovem
17.
J Nucl Med ; 62(3): 360-365, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32680925

RESUMO

99mTc-PHC-102 is a 99mTc-labeled derivative of acetazolamide, a high-affinity small organic ligand of carbonic anhydrase IX (CAIX). 99mTc-PHC-102 has previously shown favorable in vivo biodistribution properties in mouse models of CAIX-positive clear cell renal cell carcinoma (ccRCC) and colorectal cancer. In this study, we aimed to explore the targeting performance of 99mTc-PHC-102 in SPECT in patients with renal cell carcinoma while also assessing the safety and tolerability of the radiotracer. Methods: We studied 5 patients with localized or metastatic ccRCC in a microdosing regimen, after the administration of a 50-µg total of CAIX ligand and 600-800 MBq of 99mTc-PHC-102. Tissue distribution and residence time in normal organs and tumors were analyzed by serial SPECT/CT scans at 3 time points (30 min, 2 h, and 6 h) after intravenous administration. Results: In the 5 patients studied, 99mTc-PHC-102 was well tolerated and no study drug-related adverse events were recorded. In the stomach, kidneys, and gallbladder, the radiotracer showed a rapid initial uptake, which cleared over time. Localization of the study drug in primary tumors of 5 patients was observed, with favorable tumor-to-background ratios. 99mTc-PHC-102 SPECT/CT allowed the identification of 4 previously unknown lung and lymph node metastases in 2 patients. Conclusion:99mTc-PHC-102 is a promising SPECT tracer for the imaging of patients with ccRCC. This tracer has the potential to identify primary and metastatic lesions in different anatomic locations. 99mTc-PHC-102 might also serve as a companion diagnostic agent for future CAIX-targeting therapeutics.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Doses de Radiação , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Segurança
18.
Clin Nucl Med ; 46(1): 16-20, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33208624

RESUMO

PURPOSE OF THE REPORT: F-FDG PET is limited for assessment of central nervous system lymphoma (CNSL) due to physiologic tracer accumulation in the brain. We prospectively evaluated the novel PET tracer Ga-pentixafor, which targets the C-X-C chemokine receptor 4 (CXCR4), for lesion visualization and response assessment of CNSL. MATERIALS AND METHODS: Seven CNSL patients underwent Ga-pentixafor PET/MRI with contrast enhancement (CE-MRI) and diffusion-weighted sequences. The accuracy of Ga-pentixafor PET for CNSL lesion detection relative to the CE-MRI reference standard was determined. Standardized uptake values (SUVmean and SUVmax), PET-based (PTV) and MRI-based (VOLMRI) tumor volumes, and apparent diffusion coefficients (ADCs) were assessed, and correlation coefficients were calculated. Three SUVmax thresholds (41%, 50%, and 70%) were evaluated for PTV definitions (PTV41%, PTV50%, and PTV70%) and tested against VOLMRI using paired sample t tests. RESULTS: Twelve Ga-pentixafor PET/MRI examinations (including 5 follow-up scans) of 7 patients were evaluated. Ga-pentixafor PET demonstrated 18 lesions, all of which were confirmed by CE-MRI; there were no false-positive lesions on PET (accuracy, 100%). PTV41% showed the highest concordance with lesion morphology, with no significant difference compared with VOLMRI (mean difference, -0.24 cm; P = 0.45). The correlation between ADCmean and SUVmean41% (r = 0.68) was moderate. Changes in PTV41% on follow-up PET/MRI showed the same trend as VOLMRI changes, including progression of 1 lesion each in patient 1 (+456.0% PTV41% and +350.8% VOLMRI) and patient 3 (+110.4% PTV41% and +85.1% VOLMRI). CONCLUSIONS: Ga-pentixafor PET may be feasible for assessment and follow-up of CNSL. Future studies need to focus on testing its clinical value to distinguish between glioma and CNSL, and between radiation-induced inflammation and viable residual tumor.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/metabolismo , Complexos de Coordenação , Imageamento por Ressonância Magnética , Peptídeos Cíclicos , Tomografia por Emissão de Pósitrons , Receptores CXCR4/metabolismo , Adulto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur J Nucl Med Mol Imaging ; 48(5): 1650-1657, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33128131

RESUMO

BACKGROUND AND AIMS: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) is a new therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). However, identification of reliable prognostic factors is hampered by heterogeneous treatment regimens applied in previous studies. Hence, we sought clinical factors able to predict response and survival to PSMA-RLT in a homogenous group of patients, all receiving 7400 MBq every 4 weeks. PATIENTS AND METHODS: Data of 61 patients (mean age 71.6 ± 6.9 years, median basal PSA 70.7 [range 1.0-4890 µg/L]), pretreated with abiraterone/enzalutamide (75.4%) and docetaxel/cabazitaxel (68.9%), received three cycles of PSMA-RLT (mean 7321 ± 592 MBq) at four weekly intervals and were analyzed retrospectively. General medical conditions and laboratory parameters of every patients were regularly assessed. Response to therapy was based on PSA levels 1 month after the 3rd cycle. Binary logistic regression test and Kaplan-Meier estimates were used to evaluate predictors and overall survival (OS). RESULTS: Forty-nine (80.3%) patients demonstrated a therapy response in terms of any PSA decline, while 21 (19.7%) patients showed increase or no changes in their PSA levels. Baseline hemoglobin (Hb) significantly predicted PSA reductions of ≥ 50% 4 weeks after receiving the 3rd PSMA-RLT (P = 0.01, 95% CI: 1.09-2.09) with an AUC of 0.68 (95% CI: 0.54-0.81). The levels of basal Hb and basal PSA were able to predict survival of patients, both P < 0.05 (relative risk 1.51 and 0.79, 95% CI: 1.09-2.09 and 0.43-1.46), respectively. In comparison to patients with reduced basal Hb, patients with normal basal Hb levels lived significantly longer (median survival not reached vs. 89 weeks, P = 0.016). Also, patients with basal PSA levels ≤ 650 µg/L had a significantly longer survival than patients with basal PSA levels > 650 µg/L (median survival not reached vs. 97 weeks, P = 0.031). Neither pretreatments with abiraterone/enzalutamide or docetaxel/cabazitaxel nor distribution of metastasis affected survival and rate of response to PSMA-RLT. CONCLUSION: Basal Hb level is an independent predictor for therapy response and survival in patients receiving PSMA-RLT every 4 weeks. Both baseline PSA ≤ 650 µg/L and normal Hb levels were associated with longer survival.


Assuntos
Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Neoplasias de Próstata Resistentes à Castração , Idoso , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Humanos , Lutécio , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Resultado do Tratamento
20.
Int J Mol Sci ; 21(23)2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33260535

RESUMO

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of 177Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.


Assuntos
Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/terapia , Compostos Radiofarmacêuticos/uso terapêutico , Humanos , Masculino , Viés de Publicação , Compostos Radiofarmacêuticos/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
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