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2.
AJR Am J Roentgenol ; 211(2): 278-285, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29949416

RESUMO

OBJECTIVE: The purposes of this article are to increase understanding of the concepts of theranostics and peptide receptor radionuclide therapy (PRRT) as they apply to neuroendocrine tumors (NETs); review the key 1, 2, and 3 clinical trial data leading to the approval of 177Lu-tetraazacyclododecanetetraacetic acid-octreotide (177Lu-DOTATATE); and foster understanding of the practical aspects and future directions of PRRT for NETs. CONCLUSION: In January 2018, 177Lu-DOTATATE therapy was approved in the United States (previously approved in Europe in September 2017) for adult patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors, including those of the foregut, midgut, and hindgut. The results of the phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial show favorable outcomes with respect to the primary endpoint of progression-free survival and a host of secondary objectives, including overall survival, objective response rate, and quality of life measures. Patient selection is based on a number of specific factors and should be sequenced carefully with respect to other available therapies, ideally in multidisciplinary cancer conferences. Establishing the therapy at a new institution can be somewhat involved, but once it is established, the therapy is fairly straightforward to administer and is well tolerated with limited side-effects and toxicity. A number of approaches and issues are still to be worked out, and this therapy will continue to be studied and optimized.


Assuntos
Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/radioterapia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Humanos , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico , Seleção de Pacientes
3.
Am J Nucl Med Mol Imaging ; 8(2): 110-118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755844

RESUMO

We investigated the block sequential regularized expectation maximization (BSREM) algorithm. ACR phantom measurements with different count statistics and 60 PET/CT research scans from the GE Discovery 600 and 690 scanners were reconstructed using BSREM and the standard-of-care OSEM algorithm. Hot concentration recovery and cold contrast recovery were measured from the phantom data. Two experienced nuclear medicine physicians reviewed the clinical images blindly. Liver SNR liver and SUVmax of the smallest lesion detected in each patient were also measured. The relationship between the maximum and mean hot concentration recovery remained monotonic below 1.5 maximum concentration recovery. The mean cold contrast recovery remained stable even for decreasing statistics with a highest absolute difference of 4% in air and 2% in bone for each reconstruction method. The D600 images resulted in an average 30% higher SNR than the D690 data for BSREM; there was no difference in SNR results between the two scanners with OSEM. The small lesion SUVmax values on the BSREM images with ß of 250, 350 and 450, respectively were on average 80%, 60% and 43% (D690) and 42%, 29%, and 21% (D600) higher than in the case of OSEM. In conclusion, BSREM can outperform OSEM in terms of contrast recovery and organ uniformity over a range of PET tracers, but a task dependent regularization strength parameter (beta) selection may be necessary. To avoid image noise and artifacts, our results suggest that using higher beta values (at least 350) may be appropriate, especially if the data has low count statistics.

4.
Clin Nucl Med ; 43(1): 1-8, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29076913

RESUMO

OBJECTIVE: To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0. METHODS: We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria. RESULTS: The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively). CONCLUSIONS: The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.


Assuntos
Interpretação de Imagem Assistida por Computador , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Adulto Jovem
5.
J Nucl Med ; 58(12): 2004-2009, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28572487

RESUMO

The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent 18F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one (18F-FTC-146). Methods: Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry were estimated. Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to 18F-FTC-146 were reported. High accumulation of 18F-FTC-146 was observed in σ-1 receptor-dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of 18F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade 18F-FTC-146 were successful. Injection of 18F-FTC-146 is safe, and absorbed doses are acceptable. The potential of 18F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.


Assuntos
Azepinas/farmacocinética , Benzotiazóis/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Azepinas/efeitos adversos , Azepinas/síntese química , Benzotiazóis/efeitos adversos , Benzotiazóis/síntese química , Feminino , Voluntários Saudáveis , Humanos , Marcação por Isótopo , Imagem por Ressonância Magnética , Masculino , Imagem Multimodal , Radiometria , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/síntese química , Receptores sigma/efeitos dos fármacos , Receptores sigma/metabolismo , Distribuição Tecidual , Imagem Corporal Total
6.
J Clin Oncol ; 34(17): 2020-7, 2016 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-27069074

RESUMO

PURPOSE: Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma. PATIENTS AND METHODS: The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7. RESULTS: Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm. CONCLUSION: Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Fluordesoxiglucose F18 , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doença de Hodgkin/patologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Compostos Radiofarmacêuticos , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
7.
PLoS One ; 11(2): e0148628, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26890637

RESUMO

PURPOSE: (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies. EXPERIMENTAL DESIGN: For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers. RESULTS: In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model. CONCLUSIONS: 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned. TRIAL REGISTRATION: ClinicalTrials.gov NCT01186601.


Assuntos
Neoplasias Encefálicas/diagnóstico , Ácido Glutâmico/análogos & derivados , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Tirosina/análogos & derivados , Adulto , Idoso , Animais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Fluordesoxiglucose F18 , Glioblastoma/diagnóstico , Ácido Glutâmico/química , Xenoenxertos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Ratos , Tomografia Computadorizada por Raios X/métodos , Tirosina/química
8.
Radiology ; 279(3): 898-905, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26785040

RESUMO

Purpose To evaluate the normal biodistribution and kinetics of (S)-4-(3-[18F]fluoropropyl)-l-glutamic acid ((18)F FSPG) in healthy volunteers and to compare (18)F FSPG mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) with those of (18)F fluorodeoxyglucose (FDG) across a variety of organs. Materials and Methods This protocol was reviewed and approved by all appropriate regulatory authorities. An 8-mCi (±10%) dose of (18)F FSPG was given to five subjects (three women, two men), and seven whole-body positron emission tomography (PET) scans were performed 5, 10, 20, 30, 45, 150, and 240 minutes after injection. Regions of interest were analyzed on the resultant (18)F FSPG images to evaluate the kinetics of this radiotracer. The images obtained 45 minutes after injection were used to measure SUVmean and SUVmax in additional regions of the body. These values were compared with similar values obtained with (18)F FDG PET published previously. Descriptive statistics, including average and standard deviation across the five subjects, were used. (18)F FSPG SUVmean and SUVmax were compared. Results On the (18)F FSPG images obtained 45 minutes after injection, there was only low-grade background activity in the majority of analyzed regions. Prominent activity was seen throughout the pancreas. Clearance of the radiotracer through the kidneys and collection in the bladder also were seen. SUV quantification shows notable differences between (18)F FSPG and (18)F FDG in the pancreas ((18)F FSPG SUVmean, 8.2; (18)F FDG SUVmean, 1.3), stomach ((18)F FSPG SUVmax, 3.6; (18)F FDG SUVmax, 1.6), and brain ((18)F FSPG SUVmean, 0.08; (18)F FDG SUVmean, 7.8). The kinetic data showed rapid clearance of the radiotracer from the blood pool and most organs, except the pancreas. Conclusion (18)F FSPG is a PET radiopharmaceutical characterized by rapid clearance from most healthy tissues, except the pancreas and kidneys. A consistent biodistribution pattern was observed with low background uptake. The physiologic uptake of this new radiotracer throughout the body is described in more detail, which is important for improved interpretative accuracy and understanding potential clinical applications. (©) RSNA, 2016.


Assuntos
Glutamatos/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Tomografia por Emissão de Pósitrons
9.
Leuk Lymphoma ; 57(3): 604-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26159046

RESUMO

As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/terapia , Radioterapia , Adulto , Idoso , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Neoplasias do Mediastino/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Radioterapia/métodos , Estudos Retrospectivos , Rituximab , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
10.
Clin Nucl Med ; 41(6): e281-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26673240

RESUMO

PURPOSE: To analyze the biodistribution of Ga-DOTA-TATE in the normal tissues and uptake in benign, indeterminate, and malignant lesions in a population of patients with known neuroendocrine tumors (NET) using semiquantitative standardized uptake values (SUV) measurements. METHODS: One hundred four consecutively scanned patients (51 men and 53 women; mean age, 56.4 years) with confirmed diagnosis of NET underwent PET/CT 1 hour after administration of Ga-DOTA-TATE. SUVmean, and SUVmax were measured in 37 normal anatomical structures for each patient. Abnormal uptake was divided into benign, indeterminate, and malignant categories based on imaging characteristic, clinical follow-up, and pathology. RESULTS: High physiologic uptake (SUVmax > 7) was observed in spleen, renal parenchyma, adrenal glands, pituitary gland, stomach, and liver (in decreasing order). Moderate uptake (3.5-7) was present in the prostate, jejunum, pancreas, ileum, and salivary glands. Mild uptake (2-3.5) was present in the uterus, colon, thyroid, rectum, and skeleton. A total of 678 lesions (limited to 5 lesions with highest uptake per organ) were included in the analysis, including 127 benign and 54 indeterminate lesions. Uptake was significantly higher in malignant lesions than in benign lesions, but an overlap was noted between the groups. CONCLUSIONS: Ga-DOTA TATE uptake in normal and abnormal structures is highly variable in patients with NET. SUV is a useful measure for characterizing benign versus malignant lesions. Anatomical and clinical correlation may be necessary to characterize foci of intermediate uptake.


Assuntos
Tumores Neuroendócrinos/metabolismo , Compostos Organometálicos/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Distribuição Tecidual
11.
Eur J Nucl Med Mol Imaging ; 42(8): 1192-201, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25916740

RESUMO

PURPOSE: Fusion dual-tracer SPECT imaging enables physiological rather than morphological voxel-based partitioning and dosimetry for (90)Y hepatic radioembolization (RE). We evaluated its prognostic value in a large heterogeneous cohort of patients with extensive hepatic malignancy. METHODS: A total of 122 patients with primary or secondary liver malignancy (18 different cell types) underwent SPECT imaging after intraarterial injection of (99m)Tc macroaggregated albumin (TcMAA) as a simulation of subsequent (90)Y microsphere distribution, followed by administration of an excess of intravenous (99m)Tc-labelled sulphur colloid (TcSC) as a biomarker for functional liver, and a second SPECT scan. TcMAA distribution was used to estimate (90)Y radiation absorbed dose in tumour (D T) and in functional liver. Laboratory and clinical follow-up were recorded for 12 weeks after RE, and radiographic responses according to (m)RECIST were evaluated at 3 and 6 months. Dose-response relationships were determined for efficacy and toxicity. RESULTS: Patients were treated with a median of 1.73 GBq activity of resin microspheres (98 patients) or glass microspheres (24 patients), in a whole-liver approach (97 patients) or a lobar approach (25 patients). The objective response rate was 41% at 3 months and 48% at 6 months. Response was correlated with D T (P < 0.01). Median overall survival was 10.1 months (95% confidence interval 7.4 - 12.8 months). Responders lived for 36.0 months compared to 8.7 months for nonresponders (P < 0.01). Stratified for tumour cell type, D T was independently associated with survival (P < 0.01). Absorbed dose in functional liver was correlated with toxicity grade change (P < 0.05) and RE-induced liver disease (P < 0.05). CONCLUSION: Fusion dual-tracer SPECT imaging offers a physiology-based functional imaging tool to predict efficacy and toxicity of RE. This technique can be refined to define dosing thresholds for specific tumour types and treatments, but appears generally predictive even in a heterogeneous cohort.


Assuntos
Embolização Terapêutica , Neoplasias Hepáticas/diagnóstico por imagem , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Microesferas , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/uso terapêutico , Tecnécio/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/uso terapêutico
12.
Clin Nucl Med ; 40(3): e173-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25140557

RESUMO

PURPOSE: Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for detection of osseous metastasis. PATIENTS AND METHODS: Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard. RESULTS: Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by 18F-NaF/18F-FDG PET/CT. CONCLUSIONS: Combined 18F-NaF/18F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Fluoreto de Sódio , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Metástase Neoplásica/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Sensibilidade e Especificidade , Fluoreto de Sódio/administração & dosagem
13.
Clin Nucl Med ; 40(4): e228-31, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25546225

RESUMO

PURPOSE: The purpose of this study was to analyze the distribution of 18F Sodium Fluoride (18F-NaF) uptake in the normal skeleton, benign and malignant bone lesions, and extraskeletal tissues, using semiquantitative SUV measurements. PATIENTS AND METHODS: We retrospectively analyzed data from 129 patients who had 18F-NaF PET/CT at our institution for an oncological diagnosis between 2007 and 2014. There were 99 men and 30 women, 19 to 90 years old (mean [SD], 61.5 [15.5]). The range, average, and SD of SUV were measured for normal bone and extraskeletal tissues uptake for the entire patient population. A separate statistical analysis was performed to compare group A, which corresponds to the population of patient with no 18F-NaF-avid metastatic lesions, and group B, which corresponds to the population of patient with 18F-NaF-avid metastatic lesions. We also measured SUV max and SUV mean for bony metastases and degenerative changes RESULTS: The PET/CT images were acquired at 30 to 169 minutes (mean [SD], 76.5 [22.8]) after injection of 3.9 to 13.6 mCi (mean [SD], 7.3 [2.4]) of 18F-NaF. The range and mean (SD) of SUV max for 18F-NaF-avid metastasis were 4.5 to 103.3 and 25.9 (16.6) and for 18F-NaF-avid degenerative changes were 3.3 to 52.1 and 16.5 (7.9), respectively. CONCLUSIONS: Various skeletal sites have different normal SUVs. Skeletal metastases have different SUVs when compared with benign findings such as degenerative changes.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Radioisótopos de Flúor/farmacocinética , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Fluoreto de Sódio/farmacocinética , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Radiology ; 272(1): 296-300, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24956051

RESUMO

A 15-year-old girl presented with a 2-month history of 30-lb (13.6 kg) weight loss, chest and abdominal pain, nausea, bilious emesis, cough, and shortness of breath. Initial blood count (performed at an outside hospital) showed elevated white blood cell and platelet counts but low hemoglobin and hematocrit levels. On examination, she had adenopathy in the left axillary and supraclavicular regions, fullness in the left chest, and abdominal guarding. Ultrasonography (US)-guided fine-needle aspiration biopsy of the left anterior chest wall mass was nondiagnostic, and lumbar puncture and bone marrow biopsies were negative. At that time, the patient underwent several imaging studies-including chest radiography; bone scanning; contrast material-enhanced computed tomography (CT) of the chest, abdomen, and pelvis; and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT-all performed within 1 week of each other. Pertinent serum laboratory values at the time of these tests were as follows: calcium level, 17 mg/dL (4.25 mmol/L) (normal range, 8.5-10.5 mg/dL [2.1-2.6 mmol/L]); ionized calcium level, 2.3 mmol/L (normal range, 1.1-1.3 mmol/L); lipase level, 2423 U/L (normal level, <300 U/L); amylase level, 1435 U/L (normal level, <140 U/L); lactate dehydrogenase level, 253 U/L (normal level, <240 U/L), albumin level, 2.6 g/dL (26 g/L) (normal level, 3.5-5.0 g/dL [35-50 g/L]), and creatinine level, 1.7 mg/dL (150.3 µmol/L) (normal level, <1.2 mg/dL [<106.1 µmol/L]). A follow-up PET/CT scan was performed approximately 2 months later after initial therapy.


Assuntos
Diagnóstico por Imagem , Doença de Hodgkin/diagnóstico , Hipercalcemia/diagnóstico , Pancreatite/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Meios de Contraste , Diagnóstico Diferencial , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Hipercalcemia/tratamento farmacológico , Pancreatite/tratamento farmacológico , Síndromes Paraneoplásicas/tratamento farmacológico , Compostos Radiofarmacêuticos
15.
J Nucl Med ; 54(12): 2055-61, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24144563

RESUMO

UNLABELLED: Planning hepatic (90)Y radioembolization activity requires balancing toxicity with efficacy. We developed a dual-tracer SPECT fusion imaging protocol that merges data on radioactivity distribution with physiologic liver mapping. METHODS: Twenty-five patients with colorectal carcinoma and bilobar liver metastases received whole-liver radioembolization with resin microspheres prescribed as per convention (mean administered activity, 1.69 GBq). As part of standard treatment planning, all patients underwent SPECT imaging after intraarterial injection of 37 MBq of (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) to simulate subsequent (90)Y distribution. Immediately afterward, patients received 185 MBq of labeled sulfur colloid ((99m)Tc-SC) intravenously as a biomarker for normal hepatic reticuloendothelial function and SPECT was repeated. The SPECT images were coregistered and fused. A region-based method was used to predict the (90)Y radiation absorbed dose to functional liver tissue (DFL) by calculation of (99m)Tc-MAA activity in regions with (99m)Tc-SC uptake. Similarly, the absorbed dose to tumor (DT) was predicted by calculation of (99m)Tc-MAA activity in voxels without (99m)Tc-SC uptake. Laboratory data and radiographic response were measured for 3 mo, and the survival of patients was recorded. SPECT-based DT and DFL were correlated with parameters of toxicity and efficacy. RESULTS: Toxicity, as measured by increase in serum liver enzymes, correlated significantly with SPECT-based calculation of DFL at all time points (P < 0.05) (mean DFL, 27.9 Gy). Broad biochemical toxicity (>50% increase in all liver enzymes) occurred at a DFL of 24.5 Gy and above. In addition, in uni- and multivariate analysis, SPECT-based calculation of DT (mean DT, 44.2 Gy) correlated with radiographic response (P < 0.001), decrease in serum carcinoembryonic antigen (P < 0.05), and overall survival (P < 0.01). The cutoff value of DT for prediction of 1-y survival was 55 Gy (area under the receiver-operating-characteristic curve = 0.86; P < 0.01). Patients who received a DT of more than 55 Gy had a median survival of 32.8 mo, compared with 7.2 mo in patients who received less (P < 0.05). CONCLUSION: Dual-tracer (99m)Tc-MAA-(99m)Tc-SC fusion SPECT offers a physiology-based imaging tool with significant prognostic power that may lead to improved personalized activity planning.


Assuntos
Embolização Terapêutica , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Agregado de Albumina Marcado com Tecnécio Tc 99m , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiometria , Radioisótopos de Ítrio/uso terapêutico
16.
Clin Cancer Res ; 19(20): 5711-21, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23983258

RESUMO

PURPOSE: Ficlatuzumab is a novel therapeutic agent targeting the hepatocyte growth factor (HGF)/c-MET pathway. We summarize extensive preclinical work using this agent in a mouse brain orthotopic model of glioblastoma. EXPERIMENTAL DESIGN: Sequential experiments were done using eight- to nine-week-old nude mice injected with 3 × 10(5) U87 MG (glioblastoma) cells into the brain. Evaluation of ficlatuzumab dose response for this brain tumor model and comparison of its response to ficlatuzumab and to temozolamide were conducted first. Subsequently, various small-animal imaging modalities, including bioluminescence imaging (BLI), positron emission tomography (PET), and MRI, were used with a U87 MG-Luc 2 stable cell line, with and without the use of ficlatuzumab, to evaluate the ability to noninvasively assess tumor growth and response to therapy. ANOVA was conducted to evaluate for significant differences in the response. RESULTS: There was a survival benefit with ficlatuzumab alone or in combination with temozolamide. BLI was more sensitive than PET in detecting tumor cells. Fluoro-D-thymidine (FLT) PET provided a better signal-to-background ratio than 2[(18)F]fluoro-2-deoxy-d-glucose (FDG) PET. In addition, both BLI and FLT PET showed significant changes over time in the control group as well as with response to therapy. MRI does not disclose any time-dependent change. Also, the MRI results showed a temporal delay in comparison to the BLI and FLT PET findings, showing similar results one drug cycle later. CONCLUSIONS: Targeting the HGF/c-MET pathway with the novel agent ficlatuzumab appears promising for the treatment of glioblastoma. Various clinically applicable imaging modalities including FLT, PET, and MRI provide reliable ways of assessing tumor growth and response to therapy. Given the clinical applicability of these findings, future studies on patients with glioblastoma may be appropriate.


Assuntos
Anticorpos Monoclonais , Glioma/diagnóstico , Glioma/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Medições Luminescentes , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Animais , Anticorpos Monoclonais/administração & dosagem , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Glioma/tratamento farmacológico , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Xenoenxertos , Humanos , Medições Luminescentes/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Resultado do Tratamento
17.
Clin Cancer Res ; 18(19): 5427-37, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22893629

RESUMO

PURPOSE: (4S)-4-(3-[(18)F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [(18)F]FSPG) is a new tracer to image x(C)(-) transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [(18)F]FSPG in patients relative to 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG). The correlation of [(18)F]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed. EXPERIMENTAL DESIGN: Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [(18)F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [(18)F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. RESULTS: [(18)F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [(18)F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [(18)F]FSPG detected 59 of 67 (88%) [(18)F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [(18)F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [(18)F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [(18)F]FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01). CONCLUSIONS: [(18)F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [(18)F]FSPG PET may assess x(C)(-) transporter activity in patients with cancer.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Meios de Contraste , Glutamatos , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Sistema y+ de Transporte de Aminoácidos/química , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Meios de Contraste/farmacocinética , Feminino , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Glutamatos/farmacocinética , Humanos , Camundongos , Pessoa de Meia-Idade
18.
Eur J Nucl Med Mol Imaging ; 39(2): 262-70, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22065013

RESUMO

PURPOSE: Typically, (18)F-FDG PET/CT and (18)F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined (18)F-FDG/(18)F-NaF PET/CT scan with that of a separate (18)F-FDG-only PET/CT scan. METHODS: There were 62 patients enrolled in this prospective trial. All had both an (18)F-FDG-alone PET/CT scan and a combined (18)F-FDG/(18)F-NaF PET/CT scan. Of the 62 patients, 53 (85%) received simultaneous tracer injections, while 9 (15%) received (18)F-NaF subsequent to the initial (18)F-FDG dose (average delay 2.2 h). Images were independently reviewed for PET findings by two Board-Certified nuclear medicine physicians, with discrepancies resolved by a third reader. Interpreters were instructed to only report findings that were concerning for malignancy. Reading the (18)F-FDG-only scan first for half of the patients controlled for order bias. RESULTS: In 15 of the 62 patients (24%) neither the (18)F-FDG-only PET/CT scan nor the combined (18)F-FDG/(18)F-NaF PET/CT scan identified malignancy. In the remaining 47 patients who had PET findings of malignancy, a greater number of lesions were detected in 16 of 47 patients (34%) using the combined (18)F-FDG/(18)F-NaF PET/CT scan compared to the (18)F-FDG-only PET/CT scan. In 2 of these 47 patients (4%), the (18)F-FDG-only scan demonstrated soft tissue lesions that were not prospectively identified on the combined study. In 29 of these 47 patients (62%), the combined scan detected an equal number of lesions compared to the (18)F-FDG-only scan. Overall, 60 of all the 62 patients (97%) showed an equal or greater number of lesions on the combined scan than on the (18)F-FDG-only scan. CONCLUSION: The current study demonstrated that (18)F-FDG and (18)F-NaF can be combined in a single PET/CT scan by administering the two radiopharmaceuticals simultaneously or in sequence on the same day. In addition to patient convenience and reduced radiation exposure from the CT component, the combined (18)F-FDG/(18)F-NaF PET/CT scan appeared to increase the sensitivity for detection of osseous lesions compared to the (18)F-FDG-only PET/CT scan in the studied population.


Assuntos
Fluordesoxiglucose F18 , Imagem Multimodal/métodos , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Prospectivos , Compostos Radiofarmacêuticos , Fluoreto de Sódio/química
19.
Radiology ; 260(1): 182-91, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21502381

RESUMO

PURPOSE: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets α(v)ß(3) integrin, in the first volunteers imaged with this tracer. MATERIALS AND METHODS: The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/mmol ± 714 [44.4 GBq/mmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests. RESULTS: The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of (18)F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096). CONCLUSION: (18)F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.


Assuntos
Carga Corporal (Radioterapia) , Radioisótopos de Flúor/farmacocinética , Integrina alfaVbeta3/metabolismo , Oligopeptídeos/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Contagem Corporal Total , Adulto , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Especificidade de Órgãos , Projetos Piloto , Doses de Radiação , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
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