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PSMA PET/CT is a diagnostic technique for patients with prostate cancer. It makes use of a radioligand that specifically binds to 'prostate specific membrane antigen' (PSMA), expressed by the prostate cancer cells. PSMA PET has proven to be highly effective in prostate cancer diagnostics in both primary staging and re-staging. PSMA PET/CT has a much higher accuracy than traditional CT and skeletal scintigraphy for the detection of metastases, allowing metastases to be detected in an earlier stage. The clinical relevance of the improved detection is now under investigation. Staging with PSMA PET/CT sometimes leads to avoiding surgery because distant metastases are found that were not detected with conventional imaging. In the Netherlands, PSMA PET/CT is now indicated both in primary prostate cancer diagnostics for the detection of metastases and for the detection of biochemical recurrence after prostatectomy or after radiotherapy.
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Antígeno Prostático Específico , Próstata , Neoplasias de la Próstata , Cintigrafía , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/diagnóstico por imagen , Antígeno Prostático Específico/análisis , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Cintigrafía/métodosRESUMEN
Fibroblast activation protein (FAP) could be a promising target for tumor imaging and therapy, as it is expressed in >90% of epithelial cancers. A high level of FAP-expression might be associated with worse prognosis in several cancer types, including lung cancer. FAPI binds this protein and allows for labelling to Gallium-68, as well as several therapeutic radiopharmaceuticals. As FAP is only expressed at insignificant levels in adult normal tissue, FAPI provides a highly specific tumor-marker for many epithelial cancers. In this review, current information on the use of [68Ga]Ga-FAPI PET/CT in lung cancer is presented. [68Ga]Ga-FAPI shows a high uptake (standardized uptake value = SUVmax) and tumor-to-background ratio (TBR) in primary lung cancer lesions, as well as in metastatic lesions of other tumor types located in the lung and in lung cancer metastases located throughout the body. Where a comparison was made to [18F]FDG PET/CT, [68Ga]Ga-FAPI showed a similar or higher SUVmax and TBR. In brain and bone metastases, [68Ga]Ga-FAPI PET/CT outperformed [18F]FDG PET/CT. In addition to this strong diagnostic performance, a possible prognostic value of [68Ga]Ga-FAPI PET/CT in lung cancer is proposed.
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PURPOSE: To evaluate whether quantitative [18F]FDG-PET/CT assessment, including radiomic analysis of [18F]FDG-positive thyroid nodules, improved the preoperative differentiation of indeterminate thyroid nodules of non-Hürthle cell and Hürthle cell cytology. METHODS: Prospectively included patients with a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT imaging. Receiver operating characteristic (ROC) curve analysis was performed for standardised uptake values (SUV) and SUV-ratios, including assessment of SUV cut-offs at which a malignant/borderline neoplasm was reliably ruled out (≥ 95% sensitivity). [18F]FDG-positive scans were included in radiomic analysis. After segmentation at 50% of SUVpeak, 107 radiomic features were extracted from [18F]FDG-PET and low-dose CT images. Elastic net regression classifiers were trained in a 20-times repeated random split. Dimensionality reduction was incorporated into the splits. Predictive performance of radiomics was presented as mean area under the ROC curve (AUC) across the test sets. RESULTS: Of 123 included patients, 84 (68%) index nodules were visually [18F]FDG-positive. The malignant/borderline rate was 27% (33/123). SUV-metrices showed AUCs ranging from 0.705 (95% CI, 0.601-0.810) to 0.729 (0.633-0.824), 0.708 (0.580-0.835) to 0.757 (0.650-0.864), and 0.533 (0.320-0.747) to 0.700 (0.502-0.898) in all (n = 123), non-Hürthle (n = 94), and Hürthle cell (n = 29) nodules, respectively. At SUVmax, SUVpeak, SUVmax-ratio, and SUVpeak-ratio cut-offs of 2.1 g/mL, 1.6 g/mL, 1.2, and 0.9, respectively, sensitivity of [18F]FDG-PET/CT was 95.8% (95% CI, 78.9-99.9%) in non-Hürthle cell nodules. In Hürthle cell nodules, cut-offs of 5.2 g/mL, 4.7 g/mL, 3.4, and 2.8, respectively, resulted in 100% sensitivity (95% CI, 66.4-100%). Radiomic analysis of 84 (68%) [18F]FDG-positive nodules showed a mean test set AUC of 0.445 (95% CI, 0.290-0.600) for the PET model. CONCLUSION: Quantitative [18F]FDG-PET/CT assessment ruled out malignancy in indeterminate thyroid nodules. Distinctive, higher SUV cut-offs should be applied in Hürthle cell nodules to optimize rule-out ability. Radiomic analysis did not contribute to the additional differentiation of [18F]FDG-positive nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .
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Neoplasias de la Tiroides , Nódulo Tiroideo , Fluorodesoxiglucosa F18 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico por imagenRESUMEN
PURPOSE: Prospective validation of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the diagnostic accuracy of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer. MATERIALS AND METHODS: Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported. RESULTS: A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%). CONCLUSIONS: In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.
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Metástasis Linfática/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Radioisótopos de Galio , Humanos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Estudios Prospectivos , Antígeno Prostático Específico , Interpretación de Imagen Radiográfica Asistida por Computador , RadiofármacosRESUMEN
Biochemically recurrent prostate cancer (BCR) is the main indication to perform prostate-specific membrane antigen PET/CT. However, localizing BCR with prostate-specific membrane antigen PET/CT remains challenging in patients with low prostate-specific antigen (PSA) values. Here, we studied the impact of advanced PET image reconstruction methods on BCR localization and interobserver agreement with 18F-DCFPyL PET/CT scans in patients with BCR and low PSA values. Methods: Twenty-four patients with BCR and a PSA level of less than 2.0 ng/mL were included. PET images were reconstructed with 4-mm voxels and 2-mm voxels, both with and without point-spread function. All scans were interpreted by 4 nuclear medicine physicians. Additionally, PET examinations of 5 patients with primary prostate cancer and confirmed absence of lymph node metastases (after lymph node dissection) were included, to assess the risk of introducing false-positive findings when using advanced reconstruction. Calculation of BCR localization rates (scan positivity) was based on consensus among our readers (≥3 readers regarding a scan positive for BCR), as well as the individual scan interpretations of the readers. Results: In the consensus analysis, BCR localization rates were not higher using advanced reconstruction (62.5%-66.7%) than using 4-mm reconstruction (62.5%). On the basis of individual readings, however, more scans were positive using 2-mm reconstruction (74.0%; 95% confidence interval [CI], 65.0%-82.9%) (P = 0.027) and 2-mm reconstruction with point-spread function (75.0%; 95% CI, 66.2%-83.8%) (P = 0.014) than 4-mm reconstruction (65.6%; 95% CI, 56.0%-75.3%). A higher number of lesions was detected on the 2-mm scans (median, 2 lesions; interquartile range, 1-3) than the 4-mm scans (median, 1; interquartile range, 0-3; P = 0.008). The advanced reconstruction methods did not increase interobserver agreement (80.6%-84.7%), compared with the 4-mm scans (75.7%, P = 0.08-0.25). In the patients with primary prostate cancer, an equal number of false-positive lesions was observed among the different reconstruction methods (overall, n = 13). Conclusion: Applying advanced image reconstruction for 18F-DCFPyL PET/CT scans did not increase BCR localization in patients with BCR and low PSA values (reader consensus). Yet, the increased number of positive individual readings may imply that further development of image reconstruction methods holds potential to improve BCR localization. No improved interobserver agreement was observed with advanced reconstruction compared with standard 4-mm reconstruction.
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Procesamiento de Imagen Asistido por Computador , Lisina/análogos & derivados , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Urea/análogos & derivados , Anciano , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Neoplasias de la Próstata/patologíaRESUMEN
In patients with metastatic castration-resistant prostate cancer, bone is the most common site for metastases. Because of their osteoblastic character, these lesions are very suitable for treatment with bone-seeking radiopharmaceuticals (RPs). Nowadays, radium-223-chloride is the only RP with a proven benefit in overall survival, whereas the ß-emitting RPs are used for pain palliation. In the past, many trials that investigated RPs alone, or in combination with chemotherapy have been performed. Because of different designs, characteristics of included patients, and chemotherapeutical and RP regimens, interpretation of the promising data and positioning of RPs in the treatment of metastatic prostate cancer has become difficult. In this review, we provide an overview of the existing data per RP with a focus on the different RPs in combination with chemotherapy. Furthermore, we aim to clarify the benefits on pain response and quality of life. Finally, we focus on the optimal timing and use of biomarkers in the treatment of patients with castration-resistant prostate cancer with RPs.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Radiofármacos/uso terapéutico , Radio (Elemento)/uso terapéutico , Dolor en Cáncer , Ensayos Clínicos como Asunto , Terapia Combinada , Quimioterapia , Humanos , Masculino , Calidad de Vida , Radioisótopos/uso terapéutico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: Subclavian artery stenosis occurs up to 4.6% in patients who are referred for a coronary artery bypass graft (CABG). Subclavian artery stenosis can compromise the blood flow in the ipsilateral mammary artery. CASE PRESENTATION: In this case report, we describe a patient with prior history of CABG and peripheral vascular disease, who presented with recurrent chest pain symptoms. Cardiac perfusion imaging using Rubidium-82 positron emission tomography showed extensive ischaemia in the anterior wall. Coronary angiography showed an ipsilateral (left) severe subclavian stenosis, while there was no significant stenosis in the bypass grafts. Patient's symptoms resolved after percutaneous intervention of the left subclavian artery. DISCUSSION: The presence of subclavian artery stenosis can result in myocardial ischaemia after prior CABG utilizing the internal mammary artery. A history of peripheral vascular disease and a blood pressure difference between the upper extremities greater than 15 mmHg are clinical predictors of subclavian artery stenosis. Percutaneous angioplasty and stenting is considered the first-line treatment for subclavian artery stenosis. Surgical management should be considered after failure of endovascular treatment in low-surgical-risk patients.
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A 22-year-old woman was diagnosed with intermediate risk stage II Hodgkin lymphoma and treated with three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by involved-field radiation therapy. A complete metabolic remission was achieved after two cycles of ABVD, which was maintained until three years after completion of treatment. Follow-up FDG-PET/CT four years after completion of treatment, however, showed a new FDG-avid (Deauville score of 4) lesion in the right scapula, suggesting relapsed disease. Computer tomography (CT)-guided biopsy of this lesion was performed and subsequent histological examination revealed a radiation-induced giant cell granuloma.
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Positron emission tomography with the radiotracer 18F-fluoro-2-deoxy-d-glucose (FDG) plays an important role in the evaluation of bone pathology. However, FDG is not a cancer-specific agent, and knowledge of the differential diagnosis of benign FDG-avid bone alterations that may resemble malignancy is important for correct patient management, including the avoidance of unnecessary additional invasive tests such as bone biopsy. This review summarizes and illustrates the spectrum of benign bone conditions that may be FDG-avid and mimic malignancy, including osteomyelitis, bone lesions due to benign systemic diseases (Brown tumor, Erdheim-Chester disease, Gaucher disease, gout and other types of arthritis, Langerhans cell histiocytosis, and sarcoidosis), benign primary bone lesions (bone cysts, chondroblastoma, chondromyxoid fibroma, desmoplastic fibroma, enchondroma, giant cell tumor and granuloma, hemangioma, nonossifying fibroma, and osteoid osteoma and osteoblastoma), and a group of miscellaneous benign bone conditions (post bone marrow biopsy or harvest status, bone marrow hyperplasia, fibrous dysplasia, fractures, osteonecrosis, Paget disease of bone, particle disease, and Schmorl nodes). Several ancillary clinical and imaging findings may be helpful in discriminating benign from malignant FDG-avid bone lesions. However, this distinction is sometimes difficult or even impossible, and tissue acquisition will be required to establish the final diagnosis.
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Enfermedades Óseas/diagnóstico por imagen , Neoplasias Óseas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Diagnóstico Diferencial , Fluorodesoxiglucosa F18 , Humanos , NeoplasiasRESUMEN
BACKGROUND: Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. METHODS: Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m2 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital. RESULTS: Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%). CONCLUSION: Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/secundario , Ácido Etidrónico/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Prednisona/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Docetaxel , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as Re-hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with Re-HEDP and cabazitaxel in mCRPC patients. METHODS: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion. In both dose levels, cabazitaxel (4 cycles of cabazitaxel 25 mg/m + 2 cycles of cabazitaxel 20 mg/m in level 1, and 6 cycles of cabazitaxel 25 mg/m in level 2) were combined with 2 cycles of Re-HEDP 40 MBq/kg (1.1 mCi/kg) (after the second and fourth cabazitaxel cycles). Three patients were planned for each dose level, expanding to 6 patients in case of a dose-limiting toxicity (DLT). A DLT is defined as any grade 4 toxicity, or grade 3 toxicity delaying the next treatment cycle. RESULTS: Twelve patients were included, of whom 3 had progressive disease before the third cycle of cabazitaxel. In total, 1 DLT occurred (dose level 1) after treatment cycle 6 (Re-HEDP) (thrombopenia grade 3 delaying the next treatment cycle). The cohort was expanded to 6 patients, with no further DLTs. No DLT occurred in dose level 2. The most important adverse events were of hematologic origin, followed by mild fatigue and diarrhea. CONCLUSIONS: Combination therapy with cabazitaxel and Re-HEDP is feasible and generally well tolerated with similar hematologic toxicity compared with cabazitaxel monotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Ácido Etidrónico/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Taxoides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/radioterapia , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the ß-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines. MATERIALS AND METHODS: The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. RESULTS: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. CONCLUSIONS: This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP.
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Antineoplásicos/uso terapéutico , Quimioradioterapia/métodos , Ácido Etidrónico/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Neoplasias de la Próstata/terapia , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Radiofármacos/uso terapéutico , Taxoides/uso terapéutico , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Línea Celular Tumoral , Quimioterapia Adyuvante , Reparación del ADN/efectos de los fármacos , Reparación del ADN/efectos de la radiación , Docetaxel , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: Several reports have shown good performance of fluorine-18 fluorocholine (F-FCH) PET-computed tomography (CT) for parathyroid localization, although overall evidence remains scarce. We collected data from three institutions in the Netherlands and investigated the performance of F-FCH PET-CT as a second-line imaging modality. MATERIALS AND METHODS: We performed a retrospective review of all patients at least 18 years who underwent F-FCH PET-CT for biochemically proven hyperparathyroidism (HPT) and inconclusive ultrasound and sestamibi scintigraphy. Acquisition of PET images was performed 30 min after the administration of 2 MBq/kg F-FCH, together with a low-dose CT. RESULTS: PET-CT scans were performed in 33 (75%) women and 11 (25%) men with a mean age of 58.9 (range 31-80 years). Three patients had multiple endocrine neoplasia type 1, one patient had tertiary HPT because of Alport syndrome and the remaining patients had sporadic primary HPT. F-FCH PET-CT was positive in 34/44 (77.3%) cases. Of the 35 abnormal glands resected in 33 patients, F-FCH PET-CT could successfully localize 33/35 (94.3%), with only one false-positive result [positive predictive value (PPV)=97.1%]. Comparison of the 10 patients with negative PET-CT with the 34 patients with positive PET-CT showed no significant differences in age, sex, ratio of preoperative calcium, use of cinacalcet, history of neck surgery, and concomitant multinodular goiter. CONCLUSION: Our study shows excellent performance of F-FCH PET-CT in patients with HPT and inconclusive conventional imaging. Because of its favorable characteristics with high performance, prospective studies should be initiated to determine whether this new technique may replace conventional sestamibi scintigraphy as a first-line imaging modality.
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Colina/análogos & derivados , Hiperparatiroidismo/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Errores Diagnósticos , Femenino , Radioisótopos de Flúor , Humanos , Hiperparatiroidismo/cirugía , Masculino , Persona de Mediana Edad , Países Bajos , Tomografía Computarizada por Tomografía de Emisión de Positrones/estadística & datos numéricos , Radiofármacos , Estudios Retrospectivos , Tecnecio Tc 99m Sestamibi , UltrasonografíaRESUMEN
Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Descubrimiento de Drogas , Terapia Molecular Dirigida , Organofosfonatos/uso terapéutico , Radiofármacos/uso terapéutico , Animales , Humanos , Organofosfonatos/química , Radiofármacos/químicaRESUMEN
AIM: Rhenium-188-HEDP ((188)Re-HEDP) is an effective radiopharmaceutical for the palliative treatment of osteoblastic bone metastases. However, only limited data on its routine use are available and its effect on quality of life (QoL) has not been studied. Therefore, we evaluated the clinical benefit of (188)Re-HEDP in routine clinical care. PATIENTS AND METHODS: Prostate or breast cancer patients with painful bone metastases receiving (188)Re-HEDP as a routine clinical procedure were eligible for evaluation. Clinical benefit was assessed in terms of efficacy and toxicity. Pain palliation and QoL were monitored using the visual analogue scale (VAS), corrected for opioid intake, and the EORTC QLQ-C30 Global health status/QoL-scale. Thrombocyte and leukocyte nadirs were used to assess haematological toxicity. RESULTS: 45 and 47 patients were evaluable for pain palliation and QoL, respectively. After a single injection of (188)Re-HEDP, the overall pain response rate was 69% and mean VAS-scores decreased relevantly and significantly (p < 0.05). Repeated treatment resulted in similar pain response. The overall QoL response rate was 68% and mean Global health status/QoL-scores increased relevantly and significantly. Haematological side effects were mild and transient. CONCLUSION: The clinically relevant response on pain and quality of life and the limited adverse events prove clinical benefit of treatment with (188)Re-HEDP and support its use in routine clinical care. Its effectiveness appears comparable to that of external beam radiotherapy.
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Neoplasias Óseas/radioterapia , Neoplasias Óseas/secundario , Neoplasias de la Mama/radioterapia , Dolor en Cáncer/prevención & control , Dolor en Cáncer/psicología , Ácido Etidrónico/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Neoplasias de la Próstata/epidemiología , Anciano , Neoplasias Óseas/psicología , Neoplasias de la Mama/epidemiología , Dolor en Cáncer/diagnóstico , Comorbilidad , Femenino , Humanos , Masculino , Países Bajos/epidemiología , Cuidados Paliativos , Prevalencia , Neoplasias de la Próstata/psicología , Neoplasias de la Próstata/radioterapia , Calidad de Vida/psicología , Radiofármacos/uso terapéutico , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aimed to investigate the anatomic pattern of disease spread at first disease relapse compared with baseline in diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: All patients who were newly diagnosed as having DLBCL between January 2004 and June 2014 who initially achieved complete remission but who eventually developed relapsed disease during follow-up were retrospectively identified. Available histological and imaging data were used to determine which nodal regions and extranodal locations were involved at relapse. RESULTS: A total of 21 patients with relapsed DLBCL were included, of whom 8 (38.1%) presented with disease relapse at previously involved sites only, 7 (33.3%) presented with disease relapse at both previously involved and new sites, and 6 (28.6%) presented with disease relapse at new sites only. A total of 57 nodal stations and 34 extranodal locations were involved in all 21 relapsed DLBCL patients. Of these 57 involved nodal regions, 47 (82.5%) were also involved at baseline, whereas 10 (17.5%) were not involved at baseline. Of the 34 involved extranodal locations, 17 (50.0%) were also involved at baseline, whereas 17 (50.0%) were not involved at baseline. CONCLUSIONS: Relapsed DLBCL generally tends to affect previously involved sites, although close to one third of patients seem to have disease recurrence exclusively in previously uninvolved sites. The great majority of involved nodal stations at relapse are also involved at baseline, whereas only one half of involved extranodal locations at relapse are involved at baseline.
Asunto(s)
Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Anciano , Anciano de 80 o más Años , Femenino , Fluorodesoxiglucosa F18 , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Recurrencia , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y Especificidad , Tasa de SupervivenciaRESUMEN
PURPOSE: To determine the malignancy rate of bone lesions identified on FDG PET/CT in patients who have undergone CT-guided biopsy because of the suspicion of malignancy. METHODS: This single-centre retrospective study spanned eight consecutive years and included all patients who underwent both FDG PET/CT and CT-guided bone biopsy because of the suspicion of malignancy. The positive predictive value (PPV) for malignancy was calculated, and different patient and imaging characteristics were compared between malignant and benign bone lesions. RESULTS: Of 102 included patients with bone lesions that all showed FDG uptake exceeding mediastinal uptake, bone biopsy showed a malignant lesion in 91 patients, yielding a PPV for malignancy of 89.2 % (95 % CI 81.7 - 93.9 %). In the 94 patients with bone lesions that showed FDG uptake exceeding liver uptake, bone biopsy showed a malignant lesion in 83 patients, yielding a PPV for malignancy of 88.3 % (95 % CI 80.1 - 93.5 %). Higher age, bone marrow replacement of the lesion seen on CT, expansion of the lesion seen on CT, and presence of multifocal lesions on FDG PET/CT were significantly more frequent in patients with malignant lesions than in those with benign bone lesions (P = 0.044, P = 0.009, P = 0.015, and P = 0.019, respectively). Furthermore, there was a trend towards a higher incidence of cortical destruction (P = 0.056) and surrounding soft tissue mass (P = 0.063) in patients with malignant bone lesions. CONCLUSION: The PPV for malignancy of suspicious bone lesions identified on FDG PET/CT is not sufficiently high to justify changes in patient management without histopathological confirmation. Nevertheless, ancillary patient and imaging characteristics may increase the likelihood of a malignant bone lesion.