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BACKGROUND: In the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS). OBJECTIVE: To assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection. DESIGN, SETTING, AND PARTICIPANTS: This is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Each 68Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores. RESULTS AND LIMITATIONS: From December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3-42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64-0.75] vs 0.63 [0.57-0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19). CONCLUSIONS: Presurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score). PATIENT SUMMARY: The use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.
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Neoplasias da Próstata , Humanos , Masculino , Seguimentos , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgiaRESUMO
We prospectively investigated the performance of the prostate-specific membrane antigen (PSMA) ligand 68Ga-PSMA-11 for detecting prostate adenocarcinoma in patients with elevated levels of prostate-specific antigen (PSA) after initial therapy. Methods:68Ga-PSMA-11 hybrid PET was performed on 2,005 patients at the time of biochemically recurrent prostate cancer after radical prostatectomy (RP) (50.8%), definitive radiation therapy (RT) (19.7%), or RP with postoperative RT (PORT) (29.6%). The presence of prostate cancer was assessed qualitatively (detection rate = positivity rate) and quantitatively on a per-patient and per-region basis, creating a disease burden estimate from the presence or absence of local (prostate/prostate bed), nodal (N1: pelvis), and distant metastatic (M1: distant soft tissue and bone) disease. The primary study endpoint was the positive predictive value (PPV) of 68Ga-PSMA-11 PET/CT confirmed by histopathology. Results: After RP, the scan detection rate increased significantly with rising PSA level (44.8% at PSA < 0.25%-96.2% at PSA > 10 ng/mL; P < 0.001). The detection rate significantly increased with rising PSA level in each individual region, overall disease burden, prior androgen deprivation, clinical T-stage, and Gleason grading from the RP specimen (P < 0.001). After RT, the detection rate for in-gland prostate recurrence was 64.0%, compared with 20.6% prostate bed recurrence after RP and 13.3% after PORT. PSMA-positive pelvic nodal disease was detected in 42.7% after RP, 40.8% after PORT, and 38.8% after RT. In patients with histopathologic validation, the PPV per patient was 0.82 (146/179). The SUVmax of histologically proven true-positive lesions was significantly higher than that of false-positive lesions (median, 11.0 [interquartile range, 6.3-22.2] vs. 5.1 [interquartile range, 2.2-7.4]; P < 0.001). Conclusion: We confirmed a high PPV for 68Ga-PSMA-11 PET in biochemical recurrence and the PSA level as the main predictor of scan positivity.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Antagonistas de Androgênios , Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Prostatectomia/métodos , Neoplasias da Próstata/patologiaRESUMO
In light of the United States Food and Drug Administration (FDA) requirement of 21 CFR 212 current Good Manufacturing Practice (cGMP) for FDA-approved position emission tomography (PET) drugs, the University of California Los Angeles (UCLA) Biomedical Cyclotron (BMC) transformed from a pre-cGMP era academic cyclotron and radiochemistry facility to a current cGMP-compliant PET drug manufacturer. In this article, we share the financial and regulatory compliance aspects of the "transformation" required to develop a sustainable quality system to support the production of two PET drugs under Abbreviated New Drug Applications (ANDAs).
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Indústria Farmacêutica/normas , Fiscalização e Controle de Instalações/normas , Fidelidade a Diretrizes , Tomografia por Emissão de Pósitrons/normas , Radioquímica/métodos , California , Ciclotrons , Aprovação de Drogas , Humanos , Controle de Qualidade , Compostos Radiofarmacêuticos , Estados Unidos , United States Food and Drug Administration , UniversidadesRESUMO
IMPORTANCE: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. OBJECTIVE: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. MAIN OUTCOMES AND MEASURES: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. RESULTS: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. CONCLUSIONS AND RELEVANCE: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.
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Ácido Edético/análogos & derivados , Recidiva Local de Neoplasia/diagnóstico por imagem , Oligopeptídeos/uso terapêutico , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Edético/uso terapêutico , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Valor Preditivo dos Testes , Antígeno Prostático Específico , Neoplasias da Próstata/terapiaAssuntos
Radioisótopos de Gálio , Revisão da Utilização de Seguros , Seguro Saúde/economia , Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Organometálicos/economia , Centers for Medicare and Medicaid Services, U.S. , Tomada de Decisões , Custos de Cuidados de Saúde , Humanos , Seguro Saúde/legislação & jurisprudência , Imagem Multimodal , Compostos Organometálicos/química , Tomografia por Emissão de Pósitrons , Setor Privado , Nanomedicina Teranóstica/economia , Estados Unidos , United States Food and Drug AdministrationRESUMO
We evaluated observer agreement for 68Ga-DOTATATE PET/CT interpretations in patients with neuroendocrine tumor (NET). METHODS: 68Ga-DOTATATE PET/CT was performed on 50 patients with known or suspected NET of the small bowel (n = 19), pancreas (n = 14), lung (n = 4), or other location (n = 13). The images were reviewed by 7 observers, who used a standardized interpretation approach. The observers were classified as having a low level of experience (<500 scans or <5 y experience with 68Ga-DOTATATE PET/CT; n = 4) or a high level of experience (≥500 scans or ≥5 y experience with 68Ga-DOTATATE PET/CT; n = 3). Interpretation by the primary nuclear medicine physician, who had access to all clinical and imaging data, served as the reference standard. Interobserver agreement was determined by the Cohen κ statistic and intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95%CI). RESULTS: Interobserver agreement was substantial, and the median number of false findings was low for the overall scan result: that is, positive versus negative scan result (κ = 0.80; 95%CI, 0.74-0.86; false findings, 3), organ involvement (κ = 0.70; 95%CI, 0.64-0.76; false findings, 5), and lymph node involvement (κ = 0.71; 95%CI, 0.65-0.78; false findings, 6). Interobserver agreement was substantial to almost perfect, and the average absolute difference (Δ) from the reference observer was low for number of organ and lymph node metastases (organ: ICC, 0.84; 95%CI, 0.77-0.89; Δ = 0.45; lymph node: ICC, 0.77; 95%CI, 0.69-0.84; Δ = 0.45), tumor SUVmax (ICC, 0.99; 95%CI, 0.97-0.99; Δ = 0.44), and reference SUV (spleen: ICC, 0.81; Δ = 1.10; liver: ICC, 0.79; Δ = 0.62). Interpretations of appropriateness for peptide-receptor radionuclide therapy varied more significantly among observers (κ = 0.64; 95%CI, 0.57-0.70), and a higher frequency of false-positive recommendations for peptide-receptor radionuclide therapy occurred in observers with low experience than in those with high experience (range, 7-12 vs. 4-8). CONCLUSION: The interpretation of 68Ga-DOTATATE PET/CT images for NET staging is consistent among observers with low and high levels of experience. However, image-based recommendations for or against peptide-receptor radionuclide therapy require experience and training.
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Tumores Neuroendócrinos/diagnóstico por imagem , Compostos Organometálicos , Adulto , Idoso , Reações Falso-Positivas , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The contrast recovery coefficients (CRC) were evaluated for five different small animal PET scanners: GE Explore Vista, Genisys4, MiniPET-2, nanoScan PC and Siemens Inveon. The NEMA NU-4 2008 performance test with the suggested image quality phantom (NU4IQ) does not allow the determination of the CRC values for the hot regions in the phantom. This drawback of NU4IQ phantom motivated us to develop a new method for this purpose. The method includes special acquisition and reconstruction protocols using the original phantom, and results in an artificially merged image enabling the evaluation of CRC values. An advantageous feature of this method is that it stops the cold wall effect from distorting the CRC calculation. Our suggested protocol results in a set of CRC values contributing to the characterization of small animal PET scanners. GATE simulations were also performed to validate the new method and verify the evaluated CRC values. We also demonstrated that the numerical values of this parameter depend on the actual object contrast of the hot region(s) and this mainly comes from the spillover effect. This effect was also studied while analysing the background activity level around the hot rods. We revealed that the calculated background mean values depended on the target contrast in a scanner specific manner. Performing the artificially merged imaging procedure and additional simulations using the micro hollow sphere (MHS) phantom geometry, we also proved that the inactive wall around the hot spheres can have a remarkable impact on the calculated CRC. In conclusion, we have shown that the proposed artificial merging procedure and the commonly used NU4IQ phantom prescribed by the NEMA NU-4 can easily deliver reliable CRC data otherwise unavailable for the NU4IQ phantom in the conventional protocol or the MHS phantom.
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Temperatura Baixa , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/instrumentação , Animais , Artefatos , Método de Monte CarloRESUMO
We have developed an efficient, streamlined, cost-effective approach to obtain Investigational New Drug (IND) approvals from the Food and Drug Administration (FDA) for positron emission tomography (PET) imaging probes (while the FDA uses the terminology PET drugs, we are using "PET imaging probes," "PET probes," or "probes" as the descriptive terms). The required application and supporting data for the INDs were collected in a collaborative effort involving appropriate scientific disciplines. This path to INDs was successfully used to translate three [(18) F]fluoro-arabinofuranosylcytosine (FAC) analog PET probes to phase 1 clinical trials. In doing this, a mechanism has been established to fulfill the FDA regulatory requirements for translating promising PET imaging probes from preclinical research into human clinical trials in an efficient and cost-effective manner.
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Academias e Institutos , Drogas em Investigação , Imagem Molecular , Sondas Moleculares , Tomografia por Emissão de Pósitrons , Animais , Citarabina , Aprovação de Drogas , Feminino , Humanos , Masculino , Imagem Molecular/economia , Sondas Moleculares/economia , Tomografia por Emissão de Pósitrons/economia , Ratos Sprague-Dawley , Estados Unidos , United States Food and Drug AdministrationRESUMO
Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure-activity relationship study was carried out. Positron Emission Tomography (PET) using (18)F-L-1-(2'-deoxy-2'-FluoroArabinofuranosyl) Cytosine ((18)F-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = â¼1-12 nM) using the (18)F-L-FAC PET pharmacodynamic assay identified compounds demonstrating superior in vivo efficacy.
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Desoxicitidina Quinase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Linhagem Celular Tumoral , Cristalografia por Raios X , Humanos , Concentração Inibidora 50 , Cinética , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Método de Monte Carlo , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: This study sought to determine whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging allows assessment of tumor viability and proliferation in patients with soft tissue sarcomas who are treated with neoadjuvant therapy. METHODS: Twenty patients with biopsy-proven, resectable, high-grade soft tissue sarcoma underwent [(18)F]FLT PET/CT imaging before and after neoadjuvant therapy. Histologic subtypes included sarcomas not otherwise specified (n = 5), malignant peripheral nerve sheath tumors (n = 3), gastrointestinal stromal tumors (n = 3), leiomyosarcomas (n = 3), angiosarcomas (n = 2), and others (n = 4). Changes in [(18)F]FLT peak standardized uptake value (SUVpeak) were correlated with percent necrosis in excised tissue, whereas posttreatment [(18)F]FLT tumor uptake was correlated with thymidine kinase 1 (TK1) expression and Ki-67 staining indices in excised tumor tissue. RESULTS: Tumor FLT SUVpeak averaged 7.1 ± 3.7 g/mL (range, 1.9-16.1 g/mL) at baseline and decreased significantly to 2.7 ± 1.6 g/mL (range, 0.8-6.0 g/mL) at follow-up (P < .001); however, marked reductions in SUV were not specific for histopathological response. The posttreatment SUVpeak did not correlate with TK1 (P = .27) or Ki-67 expression (P = .21). CONCLUSIONS: Marked reductions in [(18)F]FLT tumor uptake in response to neoadjuvant treatment were observed in most patients with sarcoma. However, these reductions were not specific for histopathologic response to neoadjuvant therapy. Furthermore, posttreatment [(18)F]FLT tumor uptake was unrelated to tumor proliferation by Ki-67 and TK1 staining. These results question the value of [(18)F]FLT PET imaging for treatment response assessments in patients with soft tissue sarcoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluordesoxiglucose F18 , Antígeno Ki-67/metabolismo , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Sarcoma/diagnóstico por imagem , Timidina Quinase/metabolismo , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Projetos Piloto , Compostos Radiofarmacêuticos , Sarcoma/metabolismo , Sarcoma/patologia , Resultado do TratamentoRESUMO
Health care costs in the United States are increasing faster than the gross domestic product (GDP), and the growth rate of costs related to diagnostic imaging exceeds those of overall health care expenditures. Here we show that the contribution of imaging to cancer care costs pales in comparison to those of other key cost components, such as cancer drugs. Specifically, we estimate that (18)F-FDG PET or PET/CT accounted for approximately 1.5% of overall Medicare cancer care costs in 2009. Moreover, we propose that the appropriate use of (18)F-FDG PET or PET/CT could reduce the costs of cancer care. Because the U.S. health care system is complex and because it is difficult to find accurate data elsewhere, most cost and use assessments are based on published data from the U.S. Centers for Medicare & Medicaid Services.
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Diagnóstico por Imagem/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Neoplasias/diagnóstico , Análise Custo-Benefício , Humanos , Neoplasias/economia , Tomografia por Emissão de Pósitrons/economiaRESUMO
UNLABELLED: By allowing simultaneous measurements of tumor volume and metabolic activity, integrated PET/CT opens up new approaches for assessing tumor response to therapy. The aim of this study was to determine whether combined assessment of tumor volume and metabolic activity improves the accuracy of (18)F-FDG PET for predicting histopathologic tumor response in patients with soft-tissue sarcomas. METHODS: Twenty patients with locally advanced high-grade soft-tissue sarcoma (10 men and 10 women; mean age, 49 +/- 17 y) were studied by (18)F-FDG PET/CT before and after preoperative therapy. CT tumor volume (CTvol) was measured by delineating tumor borders on consecutive slices of the CT scan. Mean and maximum (18)F-FDG standardized uptake value within this volume (SUVmean and SUVmax, respectively) were determined. Two indices of total lesion glycolysis (TLG) were calculated by multiplying tumor volume by SUVmean (TLGmean) and SUVmax (TLGmax). Changes in CTvol, SUVmean, SUVmax, TLGmean, and TLGmax after chemotherapy were correlated with histopathologic tumor response (> or =95% treatment-induced tumor necrosis). Accuracy for predicting histopathologic response was compared by receiver-operating-characteristic (ROC) curve analysis. RESULTS: Baseline SUVmax, SUVmean, CTvol, TLGmean, and TLGmax were 11.22 g/mL, 2.84 g/mL, 544.1 mL, 1,619.8 g, and 8852.9 g, respectively. After neoadjuvant therapy, all parameters except CTvol showed a significant decline (DeltaSUVmax = -51%, P < 0.001; DeltaSUVmean = -40%, P < 0.001; DeltaCTvol = -14%, P = 0.37; DeltaTLGmean = -44%, P = 0.006; and DeltaTLGmax = -54%, P = 0.001). SUV changes in histopathologic responders (n = 6) were significantly more pronounced than those in nonresponders (n = 14) (P = 0.001). Histopathologic response was well predicted by changes in SUVmean and SUVmax (area under ROC curve [AUC] = 1.0 and 0.98, respectively) followed by TLGmean (AUC = 0.77) and TLGmax (AUC = 0.74). In contrast, changes in CTvol did not allow prediction of treatment response (AUC = 0.48). CONCLUSION: In this population of patients with sarcoma, TLG was less accurate in predicting tumor response than were measurements of the intratumoral (18)F-FDG concentration (SUVmax, SUVmean). Further evaluation of TLG in larger patient populations and other tumor types is necessary to determine the value of this conceptually attractive parameter for assessing tumor response.
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Tomografia por Emissão de Pósitrons/métodos , Sarcoma/diagnóstico por imagem , Sarcoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico por Imagem/métodos , Feminino , Glicólise , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos/farmacologiaRESUMO
PURPOSE: Gefitinib, an inhibitor of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK), has shown potent effects in a subset of patients carrying specific EGFR-TK mutations in advanced non-small-cell lung cancer. In this study, we asked whether PET with [(18)F]gefitinib may be used to study noninvasively the pharmacokinetics of gefitinib in vivo and to image the EGFR status of cancer cells. MATERIALS AND METHODS: Synthesis of [(18)F]gefitinib has been previously described. The biodistribution and metabolic stability of [(18)F]gefitinib was assessed in mice and vervet monkeys for up to 2 h post injection by both micropositron emission tomography (PET)/computed tomography (CT) scans and postmortem ex vivo tissue harvesting. Uptake levels of radiolabeled gefitinib in EGFR-expressing human cancer cell lines with various levels of EGFR expression or mutation status were evaluated both in vivo and in vitro. RESULTS: MicroPET/CT scans in two species demonstrated a rapid and predominantly hepatobiliary clearance of [(18)F]gefitinib in vivo. However, uptake levels of radiolabeled gefitinib, both in vivo and in vitro, did not correlate with EGFR expression levels or functional status. This unexpected observation was due to high nonspecific, nonsaturable cellular uptake of gefitinib. CONCLUSION: The biodistribution of the drug analogue [(18)F]gefitinib suggests that it may be used to assess noninvasively the pharmacokinetics of gefitinib in patients by PET imaging. This is of clinical relevance, as insufficient intratumoral drug concentrations are considered to be a factor for resistance to gefitinib therapy. However, the highly nonspecific cellular binding of [(18)F]gefitinib may preclude the use of this imaging probe for noninvasive assessment of EGFR receptor status in patients.
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Receptores ErbB/metabolismo , Radioisótopos de Flúor/farmacocinética , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Quinazolinas/farmacocinética , Animais , Linhagem Celular Tumoral , Chlorocebus aethiops , Gefitinibe , Taxa de Depuração Metabólica , Camundongos , Técnicas de Sonda Molecular , Especificidade de Órgãos , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
It is difficult to accurately forecast the clinical course of many patients presenting with mild cognitive problems. The utility in prognostic evaluation of various parameters of brain structure and function that can now be noninvasively measured remains to be clearly defined. The present work examined the value of regional cerebral metabolism, assessed with positron emission tomography (PET) and [(18)F]fluoro-2-deoxyglucose, in this context. PET scans of 167 patients (mean Mini-Mental State Examination (MMSE)=24 of 30 possible points) were classified as being positive or negative for evidence of progressive dementia. Results of scans were compared to patients' subsequent clinical course in general and in particular, to their changes in MMSE scores, for up to 10 years following PET. Data were further stratified according to the predictions of referring physicians based upon clinical assessments that had been performed up until the time of PET. Among those patients for whom a progressive dementing course had been predicted by PET criteria (but not those who were predicted by PET criteria to remain stable) a significant decline in general cognitive performance and MMSE scores occurred in the period following PET. Among those patients predicted by clinical criteria to have a progressive dementing illness, 94% of those with positive PET scans did suffer a progressive decline, while only 25% of those with negative scans progressed (relative risk 3.8). Similarly, among those patients who had been predicted by clinical criteria to remain cognitively stable, 74% of those with positive PET scans nevertheless suffered progressive decline, compared with 4% of those with negative PET scans (relative risk 18.4). These data indicate that evaluation of brain metabolism by PET in appropriately selected patients may improve the accuracy of clinical prognostic assessment.
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Encéfalo/metabolismo , Demência/diagnóstico , Tomografia Computadorizada de Emissão , Idoso , Encéfalo/diagnóstico por imagem , Demência/diagnóstico por imagem , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
Metabolic or molecular imaging with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has emerged as a powerful imaging modality for diagnosis, staging, and therapy monitoring of a variety of cancers. The accuracy of FDG-PET as an imaging tool for the primary staging of lymphoma suffers from the absence of a reference criterion to which all imaging modalities can be compared. For ethical reasons, pathological diagnosis is usually not possible for all of the lesions and abnormalities found. In this article, the current state of the art for staging of primary lymphoma is reviewed and the implications for staging and the impact on patient management discussed. Whole-body PET using FDG is superior to conventional staging, i.e., physical examination, laboratory tests, plain radiography, and CT, by 10-20%. The sensitivity of FDG-PET varies for different regions of the body and appears lowest for infradiaphragmatic disease involvement. Staging with metabolic imaging leads in 10-40% of patients to a change in clinical stage. Highly variable results have been reported on whether up- or downstaging of lymphoma with PET leads to changes in the therapeutic approach for primary lymphoma.