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1.
G Ital Nefrol ; 37(2)2020 Apr 09.
Artigo em Italiano | MEDLINE | ID: mdl-32281763

RESUMO

In recent years imaging techniques that use radionuclides have become more and more clinically relevant as they can provide functional information for specific anatomical districts. This has also involved nephrology, where radionuclides are used to study patients with different degrees of renal function failure up to terminal uremia. Although chronic kidney disease, and dialysis in particular, may affect the distribution and the elimination of radiopharmaceuticals, to date there are no consistent data on the risks associated with their use in this clinical context. In addition to the lack of data on the safety of radio-exposure in dialysis patients, there is also a shortage of information concerning the risk for healthcare staff involved in conducting the dialysis sessions performed after a nuclear test. This study, performed on 29 uremic patients who underwent hemodialysis immediately after a scintigraphic examination, assessed the extent of radio-contamination of the staff and of hemodialysis devices such as monitor, kits and dialysate. The data collected has been used to quantify the radiological risk in dialysis after the exposure to the most common radionuclides.


Assuntos
Falência Renal Crônica/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , Diálise Renal , Soluções para Diálise/química , Soluções para Diálise/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Cintilografia/efeitos adversos , Cintilografia/métodos , Compostos Radiofarmacêuticos/efeitos adversos , Medição de Risco , Uremia/metabolismo
3.
Semin Radiat Oncol ; 30(1): 68-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31727302

RESUMO

Transarterial radioembolization (TARE) with Yttrium-90 (90Y) microspheres is a liver-directed therapy for primary and metastatic disease. This manuscript provides a review of the clinical literature on TARE indications and efficacy with overviews of patient-selection and toxicity. Current dosimetry models used in practice are safe, relatively simple, and easy for clinicians to use. Planning currently relies on the imperfect surrogate, 99mTc macroaggregated albumin. Post-therapy quantitative imaging (90Y SPECT/CT or 90Y PET/CT) of microspheres can be used to calculate the macroscopic in vivo absorbed dose distribution. Similar to the evolution of other brachytherapy dose calculations, TARE is moving toward more patient-specific dosimetry that includes calculating and reporting nonuniform dose distributions throughout tumors and normal uninvolved liver.


Assuntos
Carcinoma Hepatocelular/radioterapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Humanos , Microesferas , Modelos Biológicos , Radiometria , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/uso terapêutico
4.
Expert Rev Gastroenterol Hepatol ; 13(11): 1023-1031, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31652074

RESUMO

Introduction: 177Lutetium-[DOTA°,Tyr3]octreotate (177Lu-DOTATATE) is a type of peptide receptor radionuclide therapy that garnered FDA approval in January 2018 for the treatment of somatostatin receptor-positive gastroenteropancreatic (GEP) neuroendocrine tumor (NET) patients. The therapy approval was based on findings from the randomized international phase III NETTER-1 trial as well as outcome data from a large European registry. The mechanism of the drug stems directly from its structure: a somatostatin analog (octreotate) selectively binding to somatostatin receptor expressing cells and being internalized, along with a chelated beta-emitting isotope 177Lu.Areas Covered: Herein we describe the pharmacology, clinical efficacy and adverse event data from prospective and retrospective studies with 177Lu-DOTATATE. We discuss the role of 177Lu-DOTATATE within the current treatment landscape for GEP NET patients.Expert Opinion: 177Lu-DOTATATE represents a unique addition to the treatment armamentarium for GEP NETs because of its potential to elicit tumor cytoreduction, which is rare among other existing treatment options, and prolonged disease control. Where 177Lu-DOTATATE fits into the treatment sequence for GEP NET patients remains an area of active investigation.


Assuntos
Neoplasias Gastrointestinais/radioterapia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Humanos , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Compostos Organometálicos/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Compostos Radiofarmacêuticos/efeitos adversos , Resultado do Tratamento
5.
Kaku Igaku ; 56(1): 127-134, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31554771

RESUMO

OBJECTIVE: Obtaining the information on safety and effectiveness of radiopharmaceutical synthesizer NEPTIS plug - 01 and florbetapir (18F) injection solution synthesized by NEPTIS plug - 01 from the post marketing surveillance study. METHODS: Regarding the safety evaluation, failure of device and adverse events were recorded. Regarding the effectiveness evaluation, we assessed the quality of PET images and the impact on the clinical diagnosis. RESULT: During the study period, 12 patients were enrolled. No adverse event was reported from those 12 patients. Two events in 2 patients were reported as a failure of device (In a subsequent investigation, those failures were thought to be caused by inadequacy of procedure manual, which has been revised now). For the quality of PET images, all 12 cases were "good" or "excellent", regardless of the positive or negative of amyloid plaque. The attending physician's diagnosis was changed in 9 patients following the PET imaging. CONCLUSION: NEPTIS plug-01 and florbetapir (18F) were safe and has a favorable effectiveness profile in 12 patients under daily clinical setting.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina/síntese química , Composição de Medicamentos/instrumentação , Etilenoglicóis/síntese química , Vigilância de Produtos Comercializados , Compostos Radiofarmacêuticos/síntese química , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Etilenoglicóis/administração & dosagem , Etilenoglicóis/efeitos adversos , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Placa Amiloide , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Segurança
6.
Appl Radiat Isot ; 154: 108890, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31525597

RESUMO

DNA double-strand breaks (DSBs) of peripheral blood lymphocyte were prospectively assessed in 9 patients who were injected with 201Tl-chloride and 123I-beta-methyl-p-iodophenyl-pentadecanoic acid in dual-isotope imaging. Phosphorylated H2AX (γH2AX) was used as a biomarker for detecting DSBs, and the mean number of γH2AX foci per cell was measured microscopically. Mean γH2AX foci before administration of radiopharmaceuticals and at 3, 6, and 24 h following administration were 0.22 ±â€¯0.34, 0.10 ±â€¯0.14, 0.59 ±â€¯0.46, and 0.52 ±â€¯0.40, respectively (p = n.s. for all combinations).


Assuntos
Dano ao DNA , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Imagem de Perfusão do Miocárdio/efeitos adversos , Tomografia Computadorizada de Emissão de Fóton Único/efeitos adversos , Idoso , Biomarcadores/sangue , Quebras de DNA de Cadeia Dupla , Ácidos Graxos , Feminino , Histonas/sangue , Humanos , Radioisótopos do Iodo/efeitos adversos , Iodobenzenos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos/efeitos adversos , Radioisótopos de Tálio/efeitos adversos , Tomografia Computadorizada de Emissão de Fóton Único/métodos
7.
Semin Nucl Med ; 49(5): 382-410, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31470933

RESUMO

Diagnostic radiopharmaceuticals used in nuclear medicine can cause adverse events. Information on these adverse events is available in case reports and databases but may not be readily accessible to healthcare professionals. This systematic review provides an overview of adverse events of diagnostical radiopharmaceuticals and their characteristics. A median frequency for adverse events in diagnostical radiopharmaceuticals of 1.63 (interquartile range: 1.09-2.29) per 100,000 is reported. Most common are skin and subcutaneous tissue disorders, and general disorders and administration site conditions. Many adverse events reported are minor in severity, although 6.7% can be classified as important. In rare cases, adverse events are serious and potentially life-threatening. With the introduction of new radiopharmaceuticals and the increasing use of positron emission tomography-computed tomography, previously unknown adverse events may be detected in daily practice. Future work should cover the experience of the patient with adverse events from diagnostic radiopharmaceuticals.


Assuntos
Técnicas e Procedimentos Diagnósticos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Humanos , Controle de Qualidade
8.
BMC Cancer ; 19(1): 788, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395036

RESUMO

BACKGROUND: NETTER-1 trial demonstrated high efficacy and low toxicity of four cycles of Peptide Receptor Radionuclide Therapy (PRRT) in patients with metastasized NET. The present study evaluates the outcome of further PRRT cycles in the so called salvage setting in patients after initial response to four therapy cycles and later progression. METHODS: Thirty five patients (pat.) (25 male, 10 female, 63 ± 9 years) with progressive, metastasized NET (23 small intestinal, 5 lung, 4 CUP, 1 rectal, 1 gastric and 1 paraganglioma) were included. All patients previously received 4 PRRT cycles with 177Lu-DOTATATE and showed initial response. SPECT based dosimetry was applied to determine kidney and tumor doses. Therapy response was evaluated using 68Ga-DOTATATE PET/CT (with high dose CT), CT alone or MRI (RECIST 1.1), toxicity was defined using CTCAE 5.0 criteria. 99mTc99-MAG3 scintigraphy was used to assess potential renal tubular damage. Progression free survival (PFS) and Overall survival (OS) analysis was performed with the Kaplan-Meier-method. RESULTS: The median PFS after initial PRRT was 33 months (95% CI: 30-36). The mean cumulative dose for including salvage PRRT was 44 GBq (range 33.5-47). One pat. (2.9%) showed grade 3 hematotoxicity. Kidney dosimetry revealed a mean cumulative kidney dose after a median of 6 PRRT cycles of 23.8 Gy. No grade 3 / 4 nephrotoxicity or relevant decrease in renal function was observed. Follow-up imaging was available in 32 patients after salvage therapy. Best response according to RECIST 1.1. was PR in one patient (3.1%), SD in 26 patients (81.3%) and PD in 5 patients (15.6%). PFS after salvage therapy was 6 months (95% CI: 0-16; 8 patients censored). Mean OS after initial PRRT was 105 months (95% CI: 92-119) and 51 months (95% CI: 41-61) after start of salvage therapy. Median OS was not reached within a follow-up of 71 months after initial PRRT and 25 months after start of salvage PRRT, respectively. CONCLUSIONS: Salvage therapy with 177Lu-DOTATATE is safe and effective even in patients with extensive previous multimodal therapies during disease progression and represents a feasible and valuable therapy option for progressive NET.


Assuntos
Complexos de Coordenação/uso terapêutico , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Radiofarmacêuticos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Complexos de Coordenação/administração & dosagem , Complexos de Coordenação/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Doses de Radiação , Radiometria , Compostos Radiofarmacêuticos/efeitos adversos , Receptores de Peptídeos/metabolismo , Retratamento , Terapia de Salvação , Resultado do Tratamento
9.
J Vasc Interv Radiol ; 30(9): 1317-1324, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31375450

RESUMO

PURPOSE: To compare outcomes of unresectable hepatocellular-cholangiocarcinoma (HCC-CC) with hepatocellular carcinoma (HCC) after locoregional therapy (LRT). MATERIALS AND METHODS: Consecutive patients with histologically confirmed HCC-CC or HCC treated with LRT between 2007 and 2017 were retrospectively reviewed. Ten patients (8 men; median age, 60 y) with 12 HCC-CCs (mean diameter, 4.2 cm ± 1.9; mean number, 3.7 ± 3.3) treated with chemoembolization (n = 6), yttrium-90 radioembolization (n = 2), RF ablation (n = 1), or chemoembolization/RF ablation (n = 1) were compared with 124 patients (92 men; median age, 59 y) with 134 HCCs (mean diameter, 4.8 cm ± 4.0; mean number, 2.6 ± 2.2) treated with chemoembolization (n = 51), yttrium-90 radioembolization (n = 17), RF ablation (n = 41), or chemoembolization/RF ablation (n = 15). Propensity score-matched analysis with conditional logistic regression adjusted for age, sex, LRT modality, tumor-specific features, and Child-Pugh class. Tumor-volume doubling time (TVDT) before LRT and objective response rates were compared by Kruskal-Wallis and Fisher exact test; progression-free survival (PFS) and transplant-free survival (TFS) were compared by Cox proportional hazards model. RESULTS: On univariate analysis, HCC-CC was associated with lower median TVDT (2.4 months vs 5.2 months, P = .03), objective response (30% vs 71%, P = .01), and median PFS (2.4 months vs 7.4 months, HR 4.3, 95% CI 2.2-8.4, P < .0001). Propensity score-matched analysis demonstrated greater distant progression (60% vs 30%, P = .003) and significantly shorter median PFS (2.4 months vs 6.0 months, HR 3.3, 95% CI 1.3-8.9, P = .017) for HCC-CC. No significant difference was observed in TFS (7.5 months vs 13.8 months, HR 1.5, 95% CI 0.4-6.1). CONCLUSIONS: HCC-CC was associated with reduced PFS and greater distant progression after LRT compared with HCC, indicating a need for adjunctive treatment strategies to improve outcomes.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Colangiocarcinoma/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Ablação por Radiofrequência , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Terapia Combinada , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/mortalidade , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Radioisótopos de Ítrio/efeitos adversos
10.
J Vasc Interv Radiol ; 30(8): 1185-1192, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31255499

RESUMO

PURPOSE: To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). METHODS: A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). RESULTS: Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6-18.1). Overall survival was 8.7 months (95% CI, 5.3-12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6-3.1), and LPFS was 3.1 months (95% CI, 1.3-4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1-2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. CONCLUSIONS: Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.


Assuntos
Neoplasias dos Ductos Biliares/radioterapia , Colangiocarcinoma/radioterapia , Resistencia a Medicamentos Antineoplásicos , Embolização Terapêutica/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Risco , Fatores de Tempo , Radioisótopos de Ítrio/efeitos adversos
11.
Hell J Nucl Med ; 22(2): 103-110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273351

RESUMO

OBJECTIVE: Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy. ANIMALS AND METHODS: Given the synthetic versatility of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand as a metal chelator and high demand of sugar molecules such as deoxyglucose (DG) in cancer cells, we carried out the radiosynthesis of a novel radiopharmaceutical agent, namely, 177Lu-DOTA-DG, and utilized it for imaging of cancer and also for the targeted radiation therapy of cancer tissues. RESULTS: In this study, we developed an efficient radiochemical synthesis of 177Lu-DOTA-DG and evaluated its pharmacological properties in vitro/in vivo. Our results showed DOTA-DG can be labeled with 177Lu with excellent radiochemical yield at 90oC in 30min. The resulting 177Lu-DOTA-DG exhibited high degree of stability without significant radiolysis up to 120h in human serum and phosphate buffer. Favorable pharmacokinetics profile was demonstrated by rapid blood clearance in 4T1 murine tumor mice and heterogeneous whole body biodistribution of 177Lu-DOTA-DG. Further, Comet assay experiments indicated that cancer cells treated with 177Lu-DOTA-DG showed significant higher degree of DNA damage compared to cells treated with 177Lu3+ or non-treated cells. CONCLUSION: This study showed that there is a great potential of using 177Lu-DOTA-DG as an imaging and therapeutic agent for cancer diagnosis and treatment. Furthermore, this study provides valuable information for developing novel 177Lu-labeled radiopharmaceuticals.


Assuntos
Desoxiglucose/química , Compostos Heterocíclicos com 1 Anel/química , Lutécio/uso terapêutico , Imagem Molecular/métodos , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/uso terapêutico , Animais , Transporte Biológico , Linhagem Celular Tumoral , Dano ao DNA , Estabilidade de Medicamentos , Marcação por Isótopo , Lutécio/efeitos adversos , Camundongos , Radioquímica , Radioisótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
12.
Vet Radiol Ultrasound ; 60(5): 567-574, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31155782

RESUMO

This longitudinal prospective exploratory study used serial measurements in five dogs to evaluate safety and retention of a tin-117 m (117m Sn) colloid after intra-articular injection in normal elbow joints. Each dog was deemed healthy based on physical examination, laboratory results, and radiographic evaluation of both elbows. While anesthetized, each received an MRI of both elbows, followed by fluorine-18 fluorodeoxyglucose positron emission tomography scans of both elbow joints and associated lymph nodes. Joint fluid (0.5-1.0 mL) was withdrawn aseptically from the left elbow joint, followed by intra-articular injection of 117m Sn colloid (92.5 MBq; 1-1.5 ml). Post-injection assessments included blood counts, serum chemistry panels, urinalyses, radiographs, joint fluid analyses, MRI/positron emission tomography scans, scintigraphy, and biodistribution scans. On day 45-47, each dog was euthanized and a complete postmortem examination was performed. Tissue samples were submitted for histopathology and radioisotope retention studies. Left elbow joints were decalcified and sectioned for future autoradiography. Scintigraphy, 1 day after injection, indicated slight radioisotope escape from the joint to regional lymph nodes. Serial blood, urine, feces, and organ counts indicated >99.1% of the 117m Sn activity was retained in the joint for 45-47 days. Radiation output levels were below patient release levels the day following injection. Maximum standard uptake value for the injected joint decreased. Joint fluid cytology was unchanged. No dog exhibited lameness during the study. Absence of joint damage and lack of systemic effects after injection of the 117m Sn colloid in normal canine elbow joints indicate that this agent may be safely used for radiosynoviorthesis in dogs with osteoarthritis.


Assuntos
Isótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Estanho/efeitos adversos , Animais , Cães , Injeções Intra-Articulares/veterinária , Isótopos/administração & dosagem , Estudos Longitudinais , Imagem por Ressonância Magnética/veterinária , Tomografia por Emissão de Pósitrons/veterinária , Estudos Prospectivos , Valores de Referência , Estanho/administração & dosagem
13.
Anticancer Res ; 39(6): 3071-3077, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177151

RESUMO

BACKGROUND: To compare outcomes for patients with colorectal cancer liver metastases (CRCLM) treated by drug-eluting bead chemoembolization (DEB-TACE) or radioembolization (TARE). PATIENTS AND METHODS: A single-center retrospective review was carried out on 202 patients with CRCLM, treated by DEB-TACE (n=47) or TARE (n=155) patients. Propensity-matching yielded 44 pairs. Paired statistical analysis was performed on matched pair demographics, treatment response, and survival. RESULTS: Patients treated with DEB-TACE had worse extra-hepatic metastasis (68.1 vs. 47.7%, p=0.014) and ≥10 liver lesions (42.2 vs. 68.8%, p=0.001). Matched patients treated with DEB-TACE had a trend towards worse toxicity (27% vs. 9.1% (p=0.057). Index DEB-TACE treatment was not a prognostic factor for overall survival (hazard ratio=0.94, 95% confidence intervaI=0.54-1.65; p=0.83). CONCLUSION: In the matched CRCLM cohort, there was a trend towards worse toxicity post-DEB-TACE treatment, but it was not an independent prognostic factor for survival.


Assuntos
Antineoplásicos/administração & dosagem , Quimioembolização Terapêutica/métodos , Neoplasias Colorretais/patologia , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Irinotecano/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Antineoplásicos/efeitos adversos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Neoplasias Colorretais/mortalidade , Progressão da Doença , Doxorrubicina/efeitos adversos , Feminino , Humanos , Irinotecano/efeitos adversos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
14.
J Vasc Interv Radiol ; 30(8): 1194-1200.e1, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31235408

RESUMO

PURPOSE: To evaluate the prognostic role of alpha-fetoprotein (AFP), des-gamma-carboxy protein (DCP), and modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with hepatocellular carcinoma after transarterial radioembolization (TARE). MATERIALS AND METHODS: During 2009-2016, 63 patients with AFP >20 ng/mL, DCP >20 mAU/mL, and Child-Pugh class A who were treated with TARE were evaluated using landmark and risk-of-death method after TARE. Both resin microspheres (n = 46) and glass microspheres (n = 17) were used. AFP or DCP response was defined as more than 50% decrease from baseline. mRECIST response was defined as complete or partial response. Median age was 60 years, and the proportion of male sex was 77.8% (n = 49). The proportions of patients with Barcelona Clinic Liver Cancer stages A, B, and C were 7.9% (n = 5), 46.0% (n = 29), and 46.0% (n = 29), respectively. RESULTS: At the 3-month landmark, AFP, DCP, and mRECIST responders lived longer than nonresponders (median overall survival, 75.8 vs 7.6 months for AFP; 75.8 vs 7.1 months for DCP; and 75.8 vs 10.0 months for mRECIST; all P < .05). The 6-month risk of death at the 3-month landmark was statistically different only between DCP responders and nonresponders (P = .002). In multivariate analysis, age less than 70 years (P = .024), absence of distant metastasis (P = .049), DCP response (P = .003), and mRECIST response (P = .003) were independent predictors for overall survival at the 3-month landmark after TARE. CONCLUSIONS: AFP, DCP, and mRECIST responders showed better prognosis than nonresponders after TARE, and DCP response was a more potent predictor than AFP response. Tumor marker response, as well as radiologic response, may be useful to predict post-TARE survival.


Assuntos
Biomarcadores/sangue , Carcinoma Hepatocelular/radioterapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Precursores de Proteínas/sangue , Compostos Radiofarmacêuticos/administração & dosagem , Critérios de Avaliação de Resposta em Tumores Sólidos , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Protrombina , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
15.
J Vasc Interv Radiol ; 30(8): 1201-1206, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31155499

RESUMO

This case series describes an approach for radiation segmentectomy-style treatment of hepatic tumors fed by arteries unsuitable for catheterization. The 15-patient cohort (17 cases from 2015 to 2018) included those diagnosed with liver tumors (14 hepatocellular carcinoma, 1 cholangiocarcinoma, 1 renal-cell carcinoma, and 1 metastatic colorectal carcinoma) and chosen for radioembolization via a multimodal approach. In each case, a balloon microcatheter was used to temporarily redistribute intrahepatic flow during infusion for enhanced radioembolic agent delivery to the tumor. A median of 199 Gy was delivered to a median of 3% of total liver volume. Based on modified Response Evaluation Criteria In Solid Tumors, 11 cases had complete responses and 6 had partial responses.


Assuntos
Oclusão com Balão , Embolização Terapêutica/métodos , Artéria Hepática/fisiopatologia , Circulação Hepática , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/radioterapia , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Oclusão com Balão/efeitos adversos , Embolização Terapêutica/efeitos adversos , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos
16.
Mutagenesis ; 34(3): 239-244, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31107537

RESUMO

Radiopharmaceuticals used for diagnosis or therapy induce DNA strand breaks, which may be detectable by single-cell gel electrophoresis (called comet assay). Blood was taken from patients before and at different time points after treatment with radiopharmaceuticals; blood cells were investigated by the comet assay using the percentage of DNA in the tail as the critical parameter. Whereas [225Ac]Ac-prostate-specific membrane antigen (PSMA)-617 alpha therapy showed no difference relative to the blood sample taken before treatment, beta therapy with [177Lu]Lu-PSMA-617 3 h post-injection revealed a small but significant increase in DNA strand breaks. In blood of patients who underwent positron emission tomography (PET) with either [18F]2-fluor-2-deoxy-D-glucose (FDG) or [68Ga]Ga-PSMA-11, an increase of DNA migration determined by the comet assay was not found when analysed at different time points (2-70 min) after intravenous tracer injection. Human whole blood was incubated with the targeted clinically relevant therapeutic radiopharmaceuticals [225Ac]Ac-PSMA-617, [177Lu]Lu-PSMA-617 and [90Y]Y-DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) at different activity concentrations (kBq/ml) for 5 days and then analysed by the comet assay. DNA damage increased with higher concentrations of all radiolabeled compounds tested. [177Lu]Lu-PSMA-617 caused higher blood cell radiotoxicity than equal activity concentrations of [90Y]Y-DOTA-TOC. Likewise, whole human blood was exposed to the positron emitters [18F]FDG and [68Ga]Ga-PSMA-11 in vitro for 24 h with activity concentrations ranging between 5 and 40 MBq/ml. The same activity concentration dependent elevated DNA migration was observed for both compounds although decay energies are different. This study demonstrated that the amount of DNA damage detected by the comet assay in whole human blood is similar among different positron emitters and divergent by a factor of 200 between alpha particles and beta radiation.


Assuntos
Ácidos Nucleicos Livres , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Compostos Radiofarmacêuticos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ensaio Cometa/métodos , Relação Dose-Resposta a Droga , Fluordesoxiglucose F18/efeitos adversos , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Fatores de Tempo , Adulto Jovem
18.
Int J Mol Sci ; 20(10)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137758

RESUMO

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr's tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Radioisótopos de Cobre/farmacocinética , Mieloma Múltiplo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Sindecana-1/imunologia , Zircônio/farmacocinética , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Neoplasias Ósseas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Radioisótopos de Cobre/efeitos adversos , Radioisótopos de Cobre/química , Feminino , Fluordesoxiglucose F18/farmacocinética , Camundongos , Camundongos Endogâmicos C57BL , Mieloma Múltiplo/patologia , Radioisótopos/efeitos adversos , Radioisótopos/química , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/química , Sindecana-1/química , Distribuição Tecidual , Zircônio/efeitos adversos , Zircônio/química
20.
Clin Nucl Med ; 44(6): 452-458, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30985413

RESUMO

OBJECTIVES: The study is to evaluate biodistribution, dosimetry, safety, and clinical usefulness of F-AlF-NOTA-octreotide (F-OC) PET/CT in combination with F-FDG PET/CT for detection of neuroendocrine neoplasms (NENs). METHODS: The biodistribution, dosimetry, and safety of F-OC were evaluated in 3 healthy volunteers. Twenty-two NEN patients underwent PET/CT at 60 minutes after intravenous injection of 3.7 to 4.44 MBq (0.1-0.12 mCi) per kilogram of body weight of F-OC. This was followed by F-FDG PET/CT within a 2-week period. RESULTS: F-OC was well tolerated by all healthy volunteers and NEN patients. The calculated effective dose of F-OC was 0.023 ± 0.002 mSv/MBq. In NEN patients, we observed prominent F-OC tumor uptake and high tumor-to-background ratios. Tumor uptake of F-OC was greater than that of F-FDG, and this was particularly evident in G2 NENs (median SUVmax, 45.6 vs 4.3; P < 0.015). Tumor uptake of F-OC or F-FDG was significantly correlated with tumor differentiation (P < 0.05). Dual tracer PET/CT detected more lesions and also yielded information on the biological status of tumors. CONCLUSIONS: The tracer F-OC exhibited favorable safety and dosimetry profiles. F-OC provided superior imaging of well-differentiated NENs and significantly higher tumor-to-background ratio compared with F-FDG. Combining F-FDG with F-OC PET/CT has the potential to improve NEN staging and management of patient treatment.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Radioisótopos de Gálio/efeitos adversos , Voluntários Saudáveis , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/efeitos adversos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Radiometria , Compostos Radiofarmacêuticos/efeitos adversos , Distribuição Tecidual
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