RESUMO
BACKGROUND: Radioactive tracer injections for breast cancer sentinel lymph node mapping can be painful. In this randomized trial, we compared four approaches to topical pain control for radiotracer injections. METHODS: Breast cancer patients were randomized (9 April 2021-8 May 2022) to receive the institutional standard of ice prior to injection (n = 44), or one of three treatments: ice plus a vibrating distraction device (Buzzy®; n = 39), 4% lidocaine patch (n = 44), or 4% lidocaine patch plus ice plus Buzzy® (n = 40). Patients completed the Wong-Baker FACES® pain score (primary outcome) and a satisfaction with pain control received scale (secondary). Nuclear medicine technologists (n = 8) rated perceived pain control and ease of administration for each patient. At study conclusion, technologists rank-ordered treatments. Data were analyzed as intention-to-treat. Wilcoxon rank-sum tests were used to compare pain scores of control versus pooled treatment arms (primary) and then control to each treatment arm individually (secondary). RESULTS: There were no differences in pain scores between the control and treatment groups, both pooled and individually. Eighty-five percent of patients were 'satisfied/very satisfied' with treatment received, with no differences between groups. No differences in providers' perceptions of pain were observed, although providers perceived treatments involving Buzzy© more difficult to administer (p < 0.001). Providers rated lidocaine patch as the easiest, with ice being second. CONCLUSION: In this randomized trial, no differences in patient-reported pain or satisfaction with treatment was observed between ice and other topical treatments. Providers found treatments using Buzzy® more difficult to administer. Given patient satisfaction and ease of administration, ice is a reasonable standard.
Assuntos
Anestésicos Locais , Neoplasias da Mama , Lidocaína , Manejo da Dor , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Manejo da Dor/métodos , Lidocaína/administração & dosagem , Anestésicos Locais/administração & dosagem , Linfonodo Sentinela/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Biópsia de Linfonodo Sentinela/métodos , Adulto , Seguimentos , Prognóstico , Gelo , Medição da Dor , Dor/etiologia , Dor/prevenção & controle , Dor/tratamento farmacológico , Administração TópicaRESUMO
BACKGROUND: After neoadjuvant chemotherapy (NAC), the SLN identification rate is lower and has a higher false-negative rate than that at upfront surgery. This clinical trial aimed to confirm the effectiveness of sentinel lymph node (SLN) surgery by determining the lymph node identification rate using multimodal SLN marker methods in patients with advanced breast cancer undergoing NAC. PATIENTS AND METHODS: This clinical study is a prospective single-center randomized controlled trial involving patients with breast cancer receiving NAC. Patients are randomized (1:1:1) into arm A that involves the use of radioisotope (RI) plus indocyanine green fluorescence (ICG-F); arm B, RI plus vital dye; and, arm C, ICG-F plus vital dye. A total of 348 patients are needed. An interim analysis was performed on 50% of the patients enrolled. The primary outcome of this trial was the SLN identification rate. RESULTS: Among the 164 total patients (median age 51 years), T2 and N1 were the most common clinical stages. The identification rate of SLN was 95% in arm A, 92% in arm B, and 79% in arm C. To assess superior efficacy, the one-sided endpoint was set at α < 0.0056. Arms A and C showed a difference of 0.1597 in the detection rate (p = 0.0055). CONCLUSIONS: The use of ICG-F plus vital dye for SLNB was the least effective. The results show that the choice of tracer should be radioisotope in combination with one of the other tracers to have the highest SLN identification rate when SLNB cannot be implemented conventionally due to the circumstances of each institution.
Assuntos
Neoplasias da Mama , Verde de Indocianina , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/diagnóstico por imagem , Verde de Indocianina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Seguimentos , Corantes/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Quimioterapia Adjuvante , Metástase LinfáticaRESUMO
GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.
Assuntos
Chaperona BiP do Retículo Endoplasmático , Radioisótopos de Flúor , Proteínas de Choque Térmico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Camundongos , Humanos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Flúor/farmacocinética , Distribuição Tecidual , Proteínas de Choque Térmico/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/administração & dosagem , Linhagem Celular Tumoral , Camundongos Nus , Feminino , Camundongos Endogâmicos BALB C , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/farmacocinética , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacocinéticaRESUMO
Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Lutécio , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Radioisótopos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Humanos , Camundongos , Lutécio/química , Radioisótopos/química , Radioisótopos/administração & dosagem , Embolização Terapêutica/métodos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer. METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer. RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes. CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.
Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Linfonodo Sentinela , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/patologia , Neoplasias Vulvares/diagnóstico por imagem , Neoplasias Vulvares/cirurgia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/diagnóstico por imagem , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Biópsia de Linfonodo Sentinela/métodos , Tecnécio/administração & dosagem , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos/administração & dosagem , Metástase Linfática/diagnóstico por imagemRESUMO
PURPOSE: To provide guidance, via multidisciplinary consensus statements, on the safety interactions between systemic anticancer agents (such as radiosensitizing chemotherapy, immunotherapy, targeted therapy, and peptide receptor radionuclide therapy) and transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled microspheres in the treatment of primary and metastatic liver malignancies. MATERIALS AND METHODS: A literature search identified 59 references that informed 26 statements on the safety of 90Y TARE combined with systemic therapies. Modified Delphi method was used to develop consensus on statements through online anonymous surveys of the 12 panel members representing the fields of interventional radiology, medical oncology, surgical oncology, hepatology, and pharmacy, focusing on hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), neuroendocrine tumors, metastatic breast cancer, and intrahepatic cholangiocarcinoma. RESULTS: High-level evidence was limited. Level 1 data in patients with mCRC suggest that some radiosensitizing chemotherapies (eg, oxaliplatin) require temporary dose reduction when used concomitantly with 90Y TARE, and some targeted therapies (eg, vascular endothelial growth factor inhibitors and antiangiogenic tyrosine kinase inhibitors) should be avoided for at least 4 weeks before 90Y TARE. In patients with HCC, the feasibility of 90Y TARE and immunotherapy has been demonstrated with Level 4 evidence. Data are more limited for other primary and secondary liver malignancies, and consensus statements were driven by expert opinion (Level 5). CONCLUSIONS: Given the absence of evidence-based guidelines on the safety of 90Y TARE in combination with systemic anticancer therapy, these consensus statements provide expert guidance on the potential risks when considering specific combinations.
Assuntos
Consenso , Técnica Delphi , Embolização Terapêutica , Neoplasias Hepáticas , Microesferas , Compostos Radiofarmacêuticos , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Embolização Terapêutica/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/administração & dosagem , Resultado do Tratamento , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Fatores de Risco , Medição de RiscoRESUMO
PURPOSE: To compare the outcomes of yttrium-90 transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC) with and without macrotrabecular-massive (MTM) subtypes. MATERIALS AND METHODS: Forty-one consecutive patients with HCC (male, 90.3%; mean age, 65.3 years [SD ± 10.7]) who underwent yttrium-90 TARE between September 2014 and January 2022 were grouped into the MTM-HCC (n = 17, 41.5%) and non-MTM-HCC (n = 24, 58.5%) groups based on their histopathological subtypes. Demographic, clinical, and radiological characteristics were compared. Survival, univariate, and multivariate analyses were performed, and prognostic factors were evaluated. RESULTS: In MTM-HCC group, the rates of moderately to poorly differentiated tumors were significantly higher (13/17 vs 8/16, P = .007), and new intrahepatic/extrahepatic metastases were detected more frequently (12/17 vs 15/24, P = .038). Median overall survival (OS) in the cohort was 29 months (range, 17.1-40.9 months), whereas patients with MTM-HCC had a significantly shorter median OS (20 vs 44 months, P = .014). In univariate analysis, MTM-HCC subtype (hazard ratio [HR], 2.690; P = .021), the presence of satellite nodules (HR, 3.810; P = .004), and macrovascular invasion (HR, 3.321; P = .012) were identified as significant prognostic factors. In multivariate analysis, MTM-HCC subtype and macrovascular invasion were determined as independent poor prognostic factors (P = .038 and P = .012, respectively). CONCLUSIONS: In patients with HCC treated with yttrium-90 TARE, both the rates of moderately to poorly differentiated histopathological classes and the development of intrahepatic or extrahepatic metastases were significantly higher in the MTM-HCC subtype. OS was worse in patients with MTM-HCC, and macrovascular invasion and MTM-HCC subtype were identified as independent poor prognostic factors.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Compostos Radiofarmacêuticos , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Radioisótopos de Ítrio/administração & dosagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Idoso , Embolização Terapêutica/mortalidade , Embolização Terapêutica/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Carga TumoralRESUMO
PURPOSE: To evaluate the histopathologic changes and potential correlations of tumor absorbed dose (TAD) after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CLMs). MATERIALS AND METHODS: This prospective pilot study assessed 12 patients with 13 CLMs through positron emission tomography (PET)/computed tomography (CT)-guided biopsies before, immediately after TARE (T0), and 3 weeks after TARE (T3). Subsequent sampling from the same location was enabled by fiducial placement. Biopsy samples were evaluated with hematoxylin and eosin, TUNEL, Ki67, OxPhos, caspase-3 (CC3), and pH2AX antibodies. Proliferation changes (Ki67) and double-strand DNA breaks (DSBs) were evaluated quantitatively. TAD was calculated on post-TARE PET/CT scan of the biopsy needle location at T0 and T3. RESULTS: Median TAD at 3 weeks after TARE was 162 Gy (interquartile range (IQR), 92-211 Gy). DSBs decreased significantly from T0 (median, 77%; IQR, 75%-100%) to T3 (median, 14%; IQR, 0%-54%; P = .028). A decrease in Ki67 was also documented (median, 73%; IQR, 70%-80% at T0 vs median, 41%; IQR, 0%-66% at T3; P = .046). There was a strong positive correlation between TAD and DSBs at T0 (r[9] = 0.68) and a strong negative correlation at T3 (r[10] = -0.855; P = .042 and P = .002, respectively). There was a strong negative correlation between TAD and Ki67 at both T0 (r[9] = -0.733; P = .025) and T3 (r[10] = -0.681; P = .030). Tumors that exhibited caspase-3 activation (8/13, 62%) at either T0 or T3 time point were more likely to develop progression (7/8 [88%] vs 1/5 [20%]; P = .015). CONCLUSIONS: Post-TARE biopsy can be used to assess TAD and histopathologic changes. Significant decreases in DSBs and proliferation index were noted after TARE. Post-TARE CC3 activation deserves further exploration.
Assuntos
Neoplasias Colorretais , Embolização Terapêutica , Estudos de Viabilidade , Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Radioisótopos de Ítrio , Humanos , Radioisótopos de Ítrio/administração & dosagem , Projetos Piloto , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Feminino , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Compostos Radiofarmacêuticos/administração & dosagem , Resultado do Tratamento , Fatores de Tempo , Biópsia Guiada por Imagem , Proliferação de Células , Antígeno Ki-67/metabolismo , Quebras de DNA de Cadeia Dupla , Biomarcadores Tumorais/metabolismoRESUMO
PURPOSE: To characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2-3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. RESULTS: The median follow-up period was 148 days (interquartile range [IQR], 92-273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4-215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0-135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44-5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%-98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%-100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). CONCLUSIONS: For HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Microesferas , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Agregado de Albumina Marcado com Tecnécio Tc 99m , Radioisótopos de Ítrio , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Estudos Retrospectivos , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Idoso , Embolização Terapêutica/efeitos adversos , Agregado de Albumina Marcado com Tecnécio Tc 99m/administração & dosagem , Resultado do Tratamento , Fatores de Tempo , Planejamento da Radioterapia Assistida por Computador , Idoso de 80 Anos ou mais , Software , Dosagem Radioterapêutica , AdultoRESUMO
PURPOSE: To identify factors of incomplete treatment after segmental transarterial radioembolization (TARE) for treatment-naive and solitary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 75 consecutive patients (age, 68.5 years [SD ± 8.0]; 25/75 [33.3%] women) with treatment-naive, solitary HCC underwent segmental or subsegmental TARE with glass microspheres (tumor size, 3.8 cm [SD ± 2.2]; administered dose, 222.6 Gy [SD ± 123.9]) at a single institution from November 2015 to June 2022. Radiologic response and progression-free survival (PFS) were assessed as per modified Response Evaluation Criteria in Solid Tumors. RESULTS: Complete treatment was achieved in 48 of 75 (64.0%) patients (mean follow-up, 33.2 months [SD ± 27.4]). Patients with incomplete treatment (27/75, 36%) presented with larger tumor size (5.0 [SD ± 2.5] vs 3.1 [SD ± 1.6] cm; P = .0001), with more tumors located in the watershed zone (81.5% vs 41.7%; P = .001). These patients were less likely to be bridged to transplant or resection (22.2% vs 52.1%; P = .015). Watershed tumors demonstrated worse target tumor PFS (median PFS, 19 months vs not reached; P = .0104) and overall PFS (9.1 months vs not reached; P = .0077). Watershed location was associated with worse PFS among tumors >3 cm in size (8.4 months vs not reached; P = .035) but not in tumors ≤3 cm in size (52.2 months vs not reached; P = .915). CONCLUSIONS: Tumor size and watershed location were associated with incomplete treatment after segmental TARE for HCC. Watershed tumors were associated with worse PFS, particularly tumors larger than 3 cm. These tumors may require careful treatment planning and repeated treatments to ensure a durable response.
Assuntos
Carcinoma Hepatocelular , Progressão da Doença , Embolização Terapêutica , Neoplasias Hepáticas , Microesferas , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos , Carga Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Fatores de Tempo , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Estudos Retrospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Risco , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Resultado do TratamentoRESUMO
PURPOSE: To assess the safety and effectiveness of using modified radiation lobectomy (mRL) to treat primary hepatic tumors located in the right hepatic lobe (Segments V-VIII) and to determine future liver remnant (FLR) hypertrophy. MATERIALS AND METHODS: A retrospective review was performed at a single institution to include 19 consecutive patients (7 females, 12 males) who underwent single-session mRL for right-sided primary hepatic tumors: 15 received segmentectomy plus lobectomy (segmental dose of >190 Gy and lobar dose of >80 Gy); 4 were treated with the double-segmental approach (dominant segments of >190 Gy and nondominant segments of >80 Gy). Treated tumors included 13 hepatocellular carcinoma (HCC), 4 cholangiocarcinoma (CCA), and 2 mixed-type HCC-CCA with a median dominant tumor size of 5.3 cm (interquartile range [IQR], 3.7-7.3 cm). FLR of the left hepatic lobe was measured at baseline, T1 (4-8 weeks), T2 (2-4 months), T3 (4-6 months), and T4 (9-12 months). RESULTS: Objective tumor response and tumor control were achieved in 17 of the 19 (89.5%) and 18 of the 19 (94.7%) patients, respectively. FLR hypertrophy was observed at T1 (median, 47.8%; P = .025), T2 (median, 48.4%; P = .012), T3 (median, 50.4%; P = .015), and T4 (median, 59.1%; P < .001). Patients without cirrhosis demonstrated greater hypertrophy by 6 months (median, 55.8% vs 47.2%; P = .031). One patient developed a Grade 3 adverse event (ascites requiring paracentesis) at 1-month follow-up. Grade ≥2 serum toxicities were associated with worse baseline Child-Pugh Score, serum albumin, and total bilirubin (P < .05). Among 7 patients who underwent neoadjuvant mRL, 2 underwent resection and 1 received liver transplant. CONCLUSIONS: mRL appears safe and effective for treatment of right-sided primary hepatic tumors with the benefit of promoting FLR hypertrophy.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Embolização Terapêutica/efeitos adversos , Colangiocarcinoma/radioterapia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Tempo , Carga Tumoral , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Hipertrofia , Adulto , Regeneração HepáticaRESUMO
BACKGROUND: Children with neuroblastoma receiving I-131 metaiodobenzylguanidine (MIBG) therapy require sedation-analgesia for strict radiation safety precautions during MIBG infusion and clearance. We evaluated the sedation-analgesia trends of patients undergoing MIBG therapy using the Pediatric Health Information System (PHIS) database. MATERIALS AND METHODS: Retrospective data from 476 patient encounters from the PHIS from 2010 to 2019. RESULTS: Total 240/476 (50.45%) children evaluated were under 6 years of age. Compared to 2010, in 2018 there was a decrease in benzodiazepine infusion use (60% vs. 40%, p < .04), as well as a decrease in use of opiate infusion (35% vs. 25%, p < .001). Compared to 2010, in 2018 we report an increase in the use of ketamine (from 5% to 10%, p < .002), as well as an increase in dexmedetomidine use (0% vs. 30%, p < .001). Dexmedetomidine was the most used medication in the 0-3 years age group compared to children older than 3 years of age (14.19% vs. 5.80%, p < .001). Opiate was the most used medication in children greater than 3 years compared to the 0-3-year age group (36.23 vs. 23.87, p < .05). CONCLUSION: Using PHIS data, we discovered considerable variability in the medications used for sedation in patients undergoing MIBG therapy. Although benzodiazepines and opioids were the most used agents, there was a trend toward decreasing use of benzodiazepines and opioids in these patients. Furthermore, there has been an increasing trend in the use of dexmedetomidine and ketamine.
Assuntos
3-Iodobenzilguanidina , Bases de Dados Factuais , Unidades de Terapia Intensiva Pediátrica , Neuroblastoma , Humanos , Pré-Escolar , Lactente , Criança , Masculino , Feminino , Estudos Retrospectivos , Neuroblastoma/radioterapia , 3-Iodobenzilguanidina/uso terapêutico , 3-Iodobenzilguanidina/administração & dosagem , Adolescente , Recém-Nascido , Analgesia/métodos , Analgesia/estatística & dados numéricos , Radioisótopos do Iodo/uso terapêutico , Radioisótopos do Iodo/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Seguimentos , Prognóstico , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/administração & dosagemRESUMO
BACKGROUND: PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC. METHODS: Eligible adult patients received 37 MBq (± 10%; 10 mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72 h and Day 5 ± 2 d after administration. RESULTS: [89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean ± standard deviation) (1.365 ± 0.245 mGy/MBq), kidney (1.126 ± 0.190 mGy/MBq), heart wall (1.096 ± 0.232 mGy/MBq), and spleen (1.072 ± 0.466 mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470 mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported. CONCLUSIONS: This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos , Zircônio , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Masculino , Neoplasias Renais/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Idoso , Zircônio/farmacocinética , Radioisótopos/administração & dosagem , Radioisótopos/farmacocinética , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/administração & dosagem , Distribuição Tecidual , Adulto , Japão , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/administração & dosagem , População do Leste AsiáticoRESUMO
OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.
Assuntos
Neoplasias do Endométrio , Preservação da Fertilidade , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18/administração & dosagem , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/terapia , Estudos Retrospectivos , Adulto , Preservação da Fertilidade/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do Tratamento , Recidiva Local de Neoplasia/diagnóstico por imagemRESUMO
There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.
Assuntos
Neoplasias Encefálicas , Glioma , Imagem Molecular , Neovascularização Patológica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Angiogênese , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Ácido Edético/análogos & derivados , Radioisótopos de Gálio/administração & dosagem , Glioma/diagnóstico por imagem , Glioma/patologia , Imagem Molecular/métodos , Gradação de Tumores , Neovascularização Patológica/diagnóstico por imagem , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/administração & dosagemRESUMO
Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the 18F-labeled pyridine-based benzamide derivatives N-(2-(dimethylamino)ethyl)-5-[18F]fluoropicolinamide ([18F]DMPY2) and N-(2-(dimethylamino)ethyl)-6-[18F]fluoronicotinamide ([18F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task. [18F]DMPY2 and [18F]DMPY3 were synthesized by direct radiofluorination of the bromo precursor, and radiochemical yields were â¼15-20%. Cell uptakes of [18F]DMPY2 and [18F]DMPY3 were >103-fold and 18-fold higher, respectively, in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [18F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) and [18F]DMPY3 (11.7%ID/g at 60 min) in B16F10 xenografts. MicroPET imaging of both agents demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. In particular, [18F]DMPY2 clearly visualized almost all metastatic lesions in lung and lymph nodes, with excellent image quality. [18F]DMPY2 demonstrated a significantly higher tumor-to-liver ratio than [18F]fluorodeoxyglucose ([18F]FDG) and the previously reported benzamide tracers N-[2-(diethylamino)-ethyl]-5-[18F]fluoropicolinamide ([18F]P3BZA) and N-[2-(diethylamino)-ethyl]-4-[18F]fluorobenzamide ([18F]FBZA) in B16F10-bearing or SK-MEL-3 (human melanoma)-bearing mice. In conclusion, [18F]DMPY2 might have strong potential for the diagnosis of early stage primary and metastatic melanoma using positron emission tomography (PET).
Assuntos
Melanoma/diagnóstico por imagem , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Cutâneas/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Radioisótopos de Flúor/administração & dosagem , Humanos , Camundongos , Ácidos Picolínicos/administração & dosagem , Compostos Radiofarmacêuticos/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 µL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 µL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 µL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.
Assuntos
Compostos Radiofarmacêuticos , Animais , Ratos , Compostos Radiofarmacêuticos/administração & dosagemRESUMO
Advancements in brain imaging techniques have emerged as a significant tool in detecting Alzheimer's disease (AD) progression. The complicated cascade of AD progression can be detected using radio imaging, especially with Positron emission tomography (PET). The review focus on recently introduced investigational PET tracers targeting neurofibrillary tau aggregates found typically in AD. Herein, we also address the use of different PET tracers and the clinical implementation of established and newer generation tracers. This review also intends to discuss the importance of several PET radiotracers and challenges in PET imaging.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Radioisótopos/química , Compostos Radiofarmacêuticos/química , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/química , Progressão da Doença , Hipocampo/patologia , Humanos , Emaranhados Neurofibrilares/patologia , Emaranhados Neurofibrilares/ultraestrutura , Tomografia por Emissão de Pósitrons/métodos , Córtex Pré-Frontal/patologia , Agregados Proteicos , Radioisótopos/administração & dosagem , Radioisótopos/classificação , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/classificação , Proteínas tau/análise , Proteínas tau/químicaRESUMO
Harnessing the power and flexibility of radiolabeled molecules, Cerenkov luminescence tomography (CLT) provides a novel technique for non-invasive visualisation and quantification of viable tumour cells in a living organism. However, owing to the photon scattering effect and the ill-posed inverse problem, CLT still suffers from insufficient spatial resolution and shape recovery in various preclinical applications. In this study, we proposed a total variation constrained graph manifold learning (TV-GML) strategy for achieving accurate spatial location, dual-source resolution, and tumour morphology. TV-GML integrates the isotropic total variation term and dynamic graph Laplacian constraint to make a trade-off between edge preservation and piecewise smooth region reconstruction. Meanwhile, the tetrahedral mesh-Cartesian grid pair method based on the k-nearest neighbour, and the adaptive and composite Barzilai-Borwein method, were proposed to ensure global super linear convergence of the solution of TV-GML. The comparison results of both simulation experiments and in vivo experiments further indicated that TV-GML achieved superior reconstruction performance in terms of location accuracy, dual-source resolution, shape recovery capability, robustness, and in vivo practicability. Significance: We believe that this novel method will be beneficial to the application of CLT for quantitative analysis and morphological observation of various preclinical applications and facilitate the development of the theory of solving inverse problem.
Assuntos
Processamento de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Medições Luminescentes/métodos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem , Algoritmos , Animais , Simulação por Computador , Fluordesoxiglucose F18/administração & dosagem , Imageamento Tridimensional/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Compostos Radiofarmacêuticos/administração & dosagem , Tomografia Óptica/métodos , Bexiga Urinária/metabolismoRESUMO
BACKGROUND: Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe 99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts. METHODS: The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated 99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software. RESULTS: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated 99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group. CONCLUSION: The liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.