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1.
Mol Pharm ; 16(7): 3083-3090, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117485

RESUMO

A six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a newly identified target in prostate cancer. The use of radio-labeled STEAP1-targeting antibodies with positron emission tomography (PET) may allow for detection of sites of metastatic prostate cancer and may refine patient selection for antigen-directed therapies. This was a prospective study in seven patients with metastatic castration-resistant prostate cancer who had at least one archival biopsy that was STEAP1-positive by immunohistochemistry. Patients received intravenous injections of ∼185 MBq and 10 mg of [89Zr]Zr-DFO-MSTP2109A, a humanized IgG1 monoclonal antibody directed against STEAP1. PET/CT images, blood samples, and whole-body counts were monitored longitudinally in six patients. Here, we report on safety, biodistribution, pharmacokinetics, dose estimates to normal tissues, and initial tumor targeting for this group of patients. There was no significant acute or subacute toxicity. Favorable biodistribution and enhanced lesion uptake (in both bone and soft tissue) were observed on imaging using a mass of 10 mg of DFO-MSTP2109A. The best lesion discrimination was seen at the latest imaging time, a median of 6 days postadministration. Pharmacokinetics showed a median serum T1/2 ß of 198 h, volume of central compartment of 3.54 L (similar to plasma volume), and clearance of 19.7 mL/h. The median biologic T1/2 for whole-body retention was 469 h. The highest mean absorbed doses to normal organs (mGy/MBq) were 1.18, 1.11, 0.78, 0.73, and 0.71 for liver, heart wall, lung, kidney, and spleen, respectively. Excellent targeting of metastatic prostate sites in both bone and soft tissue was observed, with an optimal imaging time of 6 days postadministration. The liver and heart were the normal organs that experienced the highest absorbed doses. The pharmacokinetics were similar to other antibodies without major cross-reactivity with normal tissues. A more detailed analysis of lesion targeting in a larger patient population with correlation to immunohistology and standard imaging modalities has been reported.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Antígenos de Neoplasias/imunologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Oxirredutases/imunologia , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/secundário , Zircônio/farmacocinética , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Reações Cruzadas/imunologia , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/metabolismo , Imunoglobulina G/uso terapêutico , Concentração Inibidora 50 , Injeções Intravenosas , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Radioisótopos/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Distribuição Tecidual , Zircônio/administração & dosagem
2.
Biol Blood Marrow Transplant ; 20(6): 881-4, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24534109

RESUMO

Whether chemosensitivity, as determined by positron emission tomography using fluorine-18-deoxyglucose (FDG-PET), is a requirement for successful allogeneic hematopoietic stem cell transplantation (allo-SCT) has yet to be established. We analyzed 88 patients with B cell non-Hodgkin lymphoma (B-NHL) for event-free (EFS) and overall survival (OS) according to computed tomography (CT) and FDG-PET criteria before uniform nonmyeloablative (NMA) allo-SCT. Patients who were chemosensitive, according to CT criteria, experienced significantly greater EFS (P < .001) and OS (P < .03) compared with those who were chemorefractory at the time of allo-SCT. Of 58 patients within this cohort who were chemosensitive by CT criteria, there was no difference in EFS (P = .85) or OS (P = .96) between FDG-PET-positive (Deauville 4 to 5, n = 24) and FDG-PET-negative (Deauville 1 to 3, n = 34) patients. There was no difference in survival according to age < or ≥ 60 years, prior autologous-stem cell transplantation, allograft characteristics, or histology. FDG-PET adds no prognostic value in chemosensitive B-NHL before NMA-allo-SCT.


Assuntos
Fluordesoxiglucose F18 , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo
3.
AJR Am J Roentgenol ; 196(3): 655-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21343510

RESUMO

OBJECTIVE: Multiple studies have defined criteria for the selection of thyroid nodules for biopsy. No set of criteria is sufficiently sensitive and specific. The aim of this study is to develop a method for assessing consistency of practice in an ultrasound group and to determine whether a 5-point malignancy rating scale can be used to select patients for biopsy. MATERIALS AND METHODS: One hundred one nodules (50 benign and 51 malignant) were selected from a thyroid biopsy database. Seven radiologists were educated on evidence-based criteria used to select nodules for biopsy. Using this information, readers graded the likelihood of malignancy using a 5-point malignancy rating scale, where 1 equals the lowest probability of malignancy and 5 equals the highest probability of malignancy, on the basis of overall impression of sonographic findings. Interobserver agreement on biopsy recommendation, reader sensitivity, specificity, and accuracy were determined. RESULTS: The sensitivity and specificity of biopsy recommendation were 96.1% and 52%, respectively. The misclassification rate was 25.7%, and accuracy was 74.3%. Interobserver agreement on biopsy recommendation was fair to substantial (κ, 0.38-0.69). The proportion of agreement was excellent for malignant nodules (0.88-1.0). The risk of malignancy increased with increasing malignancy rating: 4.3% of nodules with a malignancy rating of 1 were malignant versus 93.4% of those assigned a rating of 5. CONCLUSION: Our study illustrates a method to evaluate the standard of practice for thyroid nodule assessment among radiologists within an ultrasound group. Application of a 5-point malignancy rating scale to select nodules for biopsy is feasible and shows good diagnostic accuracy.


Assuntos
Biópsia/normas , Medicina Baseada em Evidências , Guias de Prática Clínica como Assunto , Nódulo da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Curva ROC , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia
4.
Int J Surg Pathol ; 17(5): 384-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19666947

RESUMO

The authors describe 3 cases of sclerosing angiomatoid nodular transformation (SANT) of the spleen diagnosed at Memorial Sloan-Kettering Cancer Center within a 1-year period (July 2008 to June 2009). All patients were female, older than 50, with lesions ranging in size from 2 to 4 cm. All were alive and well after splenectomy. All the cases showed characteristic histological and immunophenotypical findings as previously described in the literature, including scattered IgG4positive plasma cells in the fibrosclerotic stroma. Of the 3 patients, 2 had a history of carcinoma, and metastasis was of concern, but a PET scan in one of these patients showed minimal to absent FDG activity suggesting that this process was of a benign indolent nature. However, in 1 patient, a PET scan revealed positive FDG activity, heightening clinical concern for malignancy.


Assuntos
Hemangioma/patologia , Baço/irrigação sanguínea , Neoplasias Esplênicas/patologia , Idoso , Biomarcadores/metabolismo , Intervalo Livre de Doença , Feminino , Hemangioma/metabolismo , Hemangioma/cirurgia , Humanos , Imunoglobulina G/metabolismo , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Plasmócitos/patologia , Tomografia por Emissão de Pósitrons , Radiografia , Esclerose , Baço/diagnóstico por imagem , Esplenectomia , Neoplasias Esplênicas/metabolismo , Neoplasias Esplênicas/cirurgia
5.
J Nucl Med ; 60(11): 1517-1523, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31053681

RESUMO

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified target in prostate cancer. We evaluated the ability of PET/CT with 89Zr-DFO-MSTP2109A, an antibody that recognizes STEAP1, to detect lesions in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Nineteen mCRPC patients were prospectively imaged using approximately 185 MBq/10 mg of 89Zr-DFO-MSTP2109A. 89Zr-DFO-MSTP2109A PET/CT images obtained 4-7 d after injection were compared with bone and CT scans. Uptake in lesions was measured. Fifteen patients were treated with an antibody-drug conjugate (ADC) based on MSTP2109A; ADC treatment-related data were correlated with tumor uptake by PET imaging. Bone or soft-tissue biopsy samples were evaluated. Results: No significant toxicity occurred. Excellent uptake was observed in bone and soft-tissue disease. Median SUVmax was 20.6 in bone and 16.8 in soft tissue. Sixteen of 17 lesions biopsied were positive on 89Zr-DFO-MSTP2109A, and all sites were histologically positive (1 on repeat biopsy). Bayesian analysis resulted in a best estimate of 86% of histologically positive lesions being true-positive on imaging (95% confidence interval, 75%-100%). There was no correlation between SUVmax tumor uptake and STEAP1 immunohistochemistry, survival after ADC treatment, number of ADC treatment cycles, or change in prostate-specific antigen level. Conclusion:89Zr-DFO-MSTP2109A is well tolerated and shows localization in mCRPC sites in bone and soft tissue. Given the high SUV in tumor and localization of a large number of lesions, this reagent warrants further exploration as a companion diagnostic in patients undergoing STEAP1-directed therapy.


Assuntos
Antígenos de Neoplasias/imunologia , Imunoconjugados/imunologia , Oxirredutases/imunologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos , Zircônio , Idoso , Idoso de 80 Anos ou mais , Humanos , Imunoconjugados/farmacocinética , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Radiometria , Distribuição Tecidual
6.
J Nucl Med ; 59(1): 161-166, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28637800

RESUMO

Trastuzumab with chemotherapy improves clinical outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive esophagogastric adenocarcinoma (EGA). Despite the therapeutic benefit, responses are rarely complete, and most patients develop progression. To our knowledge, this is the first report evaluating 89Zr-trastuzumab in HER2-positive EGA; here, we evaluate the safety, pharmacokinetics, biodistribution, and dosimetry 89Zr-trastuzumab. Methods: Trastuzumab was conjugated with deferoxamine and radiolabeled with 89Zr. A mean activity of 184 MBq was administered to 10 patients with metastatic HER2-positive EGA. PET imaging, whole-body probe counts, and blood draws were performed to assess pharmacokinetics, biodistribution, and dosimetry. Results: No clinically significant toxicities were observed. At the end of infusion, the estimated 89Zr-trastuzumab in plasma volume was a median 102% (range, 78%-113%) of the injected dose. The median biologic half-life T1/2ß was 111 h (range, 78-193 h). The median biologic whole-body retention half-life was 370 h (range, 257-578 h). PET images showed optimal tumor visualization at 5-8 d after injection. The maximum tumor SUV ranged from no to minimal uptake in 3 patients to a median of 6.8 (range, 2.9-22.7) for 20 lesions in 7 patients. Dosimetry estimates from OLINDA showed that the organs receiving the highest absorbed doses were the liver and heart wall, with median values of 1.37 and 1.12 mGy/MBq, respectively. Conclusion:89Zr-trastuzumab imaging tracer is safe and provides high-quality images in patients with HER2-positive EGA, with an optimal imaging time of 5-8 d after injection.


Assuntos
Adenocarcinoma/metabolismo , Anticorpos Monoclonais Humanizados/farmacocinética , Junção Esofagogástrica/diagnóstico por imagem , Neoplasias Gástricas/metabolismo , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Anticorpos Monoclonais Humanizados/sangue , Feminino , Humanos , Masculino , Metástase Neoplásica , Tomografia por Emissão de Pósitrons , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Distribuição Tecidual
7.
Clin Nucl Med ; 37(8): 759-62, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22785503

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm with propensity for nodal metastases. A few reports have presented imaging results with FDG PET/CT or 111In-pentetreotide (OctreoScan, OCT) indicating a higher sensitivity for FDG than OCT, but no reports have directly compared FDG to OCT in the same patients. We reviewed our experience in a limited number of patients who underwent both procedures. METHODS: Patients with MCC who had FDG PET and OCT between 2000 and 2010 in our center were retrospectively reviewed. Patients were included if they had FDG PET/CT and OCT scan within a 2-month interval. For each eligible patient, we compared all abnormal lesions identified on either scan. The findings were verified by pathology or other imaging techniques up to a 4-month follow-up. RESULTS: A total of 9 patients met the selection criteria with 10 dual scans (1 was scanned twice). Three patients had no documented sites of disease at the time of imaging. One patient had negative findings on both FDG and OCT initially, but 1 year later developed FDG-positive OCT-negative disease. Five patients had metastatic disease at the time of imaging: 2 were negative on OCT and positive on FDG; the other 3 were positive on both scans but had more lesions on FDG. CONCLUSIONS: Our data on a small number of patients are in agreement with prior individual FDG or OCT reports and suggest that, overall, FDG PET/CT detects more MCC lesions and upgrades MCC stage compared with the OCT scan. Importantly, there were no lesions identified by OCT that were missed by PET. Thus, given the added resolution and sensitivity of PET, the use of OCT in MCC in the modern era is of limited value and it remains to be seen whether newer 68Ga-labeled somatostatin analogs will perform better than OCT.


Assuntos
Carcinoma de Célula de Merkel/diagnóstico por imagem , Fluordesoxiglucose F18 , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Somatostatina/análogos & derivados , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Imagem Corporal Total
8.
J Clin Ultrasound ; 33(7): 321-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16196004

RESUMO

PURPOSE: To study the ability and accuracy of sonography to visualize carotid artery stents and assess criteria for carotid artery stent stenosis. METHODS: Duplex Doppler sonographic examinations were performed on 143 patients in whom 158 carotid artery stents were placed. Follow-up sonography to evaluate 24 of these stents within 24 h of stent placement was compared with post-procedure angiography. Another 23 stents were evaluated with sonography and with follow-up angiography more than 24 h after the procedure. The remainder of the 111 stents were evaluated exclusively with sonography after stent placement. Sonography was used to evaluate stent visibility, stent-media separation, and degree of stent stenosis. RESULTS: Wallstents were the best-visualized stents and Acculink the worst, but the differences were not statistically significant. Of 4 patients with stent-media separation >3 mm, 2 (50%) developed stenosis (40%-59%) at 6 and 12 months from stent placement. The other 2 stents with stent-media separation had not developed stenosis at 6 months' follow-up. A comparison of angiography and sonography performed on the date of stent placement revealed 19 true-negative sonography studies, 4 false-positive studies, 1 true-positive study, and no false-negative studies. A comparison of follow-up angiograms performed more than 24 h after the procedure with follow-up sonography revealed 17 true-negative studies, 1 false-positive study, 5 true-positive studies, and no false-negative studies. CONCLUSIONS: Sonography allows accurate evaluation of stent placement within the vessel and visualization of stent-media distance. Stent-media separation may be an early detection sign for stent stenosis development. Velocity criteria developed for non-stented vessels, when applied to stented vessels, correlate well with angiographic findings. Doppler velocity measurements when compared with visible stent assessment may reduce false-positives.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Stents , Ultrassonografia Doppler Dupla , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Sensibilidade e Especificidade
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