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3.
Mol Pharm ; 21(5): 2425-2434, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38554143

RESUMO

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/farmacocinética
4.
J Vasc Interv Radiol ; 35(5): 712-721.e3, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38336031

RESUMO

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 Tratamento
5.
J Vasc Interv Radiol ; 35(5): 722-730.e1, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38342221

RESUMO

PURPOSE: To investigate if combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization results in superior outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC). METHODS: A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included. Propensity score matching was conducted to account for baseline demographic differences. Kaplan-Meier analysis was used to compare median progression-free survival (PFS) and overall survival (OS), and univariate statistics identified disease response and control rate differences. Duration of imaging response was defined as number of months between the first scan after therapy and the first scan showing progression as defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or immune Response Evaluation Criteria in Solid Tumors (iRECIST). Adverse events were analyzed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Patients in the 90Y+ICI therapy group had better objective response rates (ORRs) (89.5% vs 36.8%; P < .001) and disease control rates (DCRs) (94.7% vs 63.2%; P < .001) by mRECIST and iRECIST (ORR: 78.9% vs 36.8%; P < .001; DCR: 94.7% vs 63.2%; P < .001). Median PFS (8.3 vs 4.1 months; P = .37) and OS (15.8 vs 14.3 months; P = .52) were not statistically different. Twelve patients (63.1%) in the 90Y+TKI group did not complete systemic therapy owing to adverse effects compared with 1 patient (5.3%) in the 90Y+ICI group (P < .001). Grade 3/4 adverse events were not statistically different (90Y+TKI: 21.1%; 90Y+ICI: 5.3%; P = .150). CONCLUSIONS: Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Inibidores de Proteínas Quinases , Compostos Radiofarmacêuticos , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/administração & dosagem , Idoso , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Embolização Terapêutica/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Fatores de Tempo , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/administração & dosagem , Intervalo Livre de Progressão , Fatores de Risco , Adulto , Idoso de 80 Anos ou mais
6.
J Vasc Interv Radiol ; 35(5): 689-698.e3, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38246416

RESUMO

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 , Adulto
7.
Int J Cardiovasc Imaging ; 40(4): 887-895, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265540

RESUMO

PURPOSE: Study aims to investigate the consistency of delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18F-FDG PET myocardial imaging in evaluating myocardial viability before CABG. METHODS: The study analyzed data from 100 patients who were examined with DE-CMR, PET imaging, and echocardiography before and after CABG. All subjects were followed up for 6-12 month post- CABG. RESULTS: DE-CMR and PET imaging have high consistency (90.1%; Kappa value = 0.71, p < 0.01) in determining myocardial viability. The degree of delayed enhancement was negatively correlated with the improvement in myocardial contractile function in this segment after revascularization (P < 0.001). The ratio of scarred myocardial segments and total DE score was significantly lower in the improvement group than non-improvement group. Multivariate regression identified that hibernating myocardium (OR = 1.229, 95%CI: 1.053-1.433, p = 0.009) was influencing factor of LVEF improvement after CABG. CONCLUSION: Both imaging techniques are consistent in evaluating myocardial viability. Detecting the number of hibernating myocardium by PET is also important to predict the left heart function improvement after CABG.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana , Fluordesoxiglucose F18 , Imagem de Perfusão do Miocárdio , Miocárdio , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Sobrevivência de Tecidos , Função Ventricular Esquerda , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fluordesoxiglucose F18/administração & dosagem , Miocárdio/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Imagem de Perfusão do Miocárdio/métodos , Fatores de Tempo , Resultado do Tratamento , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Recuperação de Função Fisiológica , Volume Sistólico , Reprodutibilidade dos Testes , Miocárdio Atordoado/diagnóstico por imagem , Miocárdio Atordoado/fisiopatologia , Miocárdio Atordoado/etiologia , Imagem Multimodal , Imageamento por Ressonância Magnética , Contração Miocárdica , Circulação Coronária , Estudos Retrospectivos
8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(5): 982-988, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37879928

RESUMO

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 & dosagem
9.
Opt Express ; 30(2): 1422-1441, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209303

RESUMO

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/metabolismo
10.
Drug Deliv ; 29(1): 186-191, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35191342

RESUMO

The treatment of bone metastatsis as primary bone cancer itself is still a challenge. The use od radium dichloride ([223Ra] RaCl2) has emerged in the last few years as one of the best treatment choice for bone cancer, with especial focus in bone metastasis. The alpha-emitter radiopharmaceutical has showed potent and efficient results in several clinical trials. In this study we have formulated radium dichloride ([223Ra] RaCl2) nanomicelles in order to evaluate and compare with pure radium dichloride ([223Ra] RaCl2). The results showed that nanomicelles at the same dose had a superior effect (20% higher efficient) when compared with pure radium dichloride ([223Ra] RaCl2). The results corroborated the effectiveness of the nanosystem validating the application of nanotechnology in alpha-radiotherapy with radium dichloride ([223Ra] RaCl2).


Assuntos
Neoplasias Ósseas/patologia , Nanopartículas/química , Osteossarcoma/patologia , Compostos Radiofarmacêuticos/farmacologia , Rádio (Elemento)/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Humanos , Micelas , Tamanho da Partícula , Poloxâmero/química , Radioisótopos/administração & dosagem , Radioisótopos/farmacologia , Compostos Radiofarmacêuticos/administração & dosagem , Rádio (Elemento)/administração & dosagem
11.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 41(1): 3-10, ene-feb. 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-205137

RESUMO

Objetivo: En este estudio, se tuvo como objetivo determinar el papel pronóstico del valor de captación máximo estandarizado (SUVmáx) basal obtenido por PET/TC antes del tratamiento, y el cambio en el SUVmáx (ΔSUVmáx [%]) en pacientes con cáncer de mama con ganglios linfáticos axilares positivos en tratamiento con quimioterapia neoadyuvante (NAC).Métodos: Se evaluaron en el estudio 180 pacientes con SUVmáx basal y 121 pacientes con medición de SUVmáx después del tratamiento. Se midieron el valor de SUVmáx inicial de la mama (SUVmáxBI) y axila (SUVmáxAI), y el cambio en el SUVmáx de la mama (ΔSUVmáxB) y axila (ΔSUVmáxA). El valor de corte óptimo de SUVmáx y ΔSUVmáx se determinó mediante el análisis de la curva ROC. La supervivencia libre de enfermedad (SSE) y la supervivencia global (SG) se calcularon mediante curvas de Kaplan-Meier.Resultados: Se encontró que los parámetros ΔSUVmáxB, pCRB, pCRA y pCR se asociaron con la recaída (p <0.001, p =0.033, p =0.016 y p =0.013, respectivamente). ΔSUVmáxB y SUVmáxAI se asociaron con la mortalidad (p=0,001 y p=0,006, respectivamente). El análisis de regresión de Cox múltiple reveló que el valor de ΔSUVmáxB era un factor pronóstico independiente para la recaída y la mortalidad (p = 0,013 y p = 0,010, respectivamente).Conclusión: Los resultados muestran que ΔSUVmáxB es un factor pronóstico independiente de recaída y mortalidad en pacientes con cáncer de mama con ganglios linfáticos axilares positivos que recibieron NAC (AU)


Objective: This study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC).Methods: One hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves.Results: ΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively).Conclusion: The results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC (AU)


Assuntos
Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Fluordesoxiglucose F18/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico
12.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055005

RESUMO

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.


Assuntos
Compostos Radiofarmacêuticos/administração & dosagem , Biomarcadores , Tomada de Decisão Clínica , Gerenciamento Clínico , Monitoramento de Medicamentos , Humanos , Terapia de Alvo Molecular , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Obesidade/etiologia , Especificidade de Órgãos/efeitos dos fármacos , Prognóstico , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacologia , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do Tratamento
13.
BMC Cancer ; 22(1): 79, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042456

RESUMO

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.


Assuntos
Glioma/diagnóstico por imagem , Oligonucleotídeos Antissenso/administração & dosagem , Compostos de Organotecnécio/administração & dosagem , RNA Longo não Codificante/análise , Compostos Radiofarmacêuticos/administração & dosagem , Animais , Modelos Animais de Doenças , Xenoenxertos/metabolismo , Lipossomos , Camundongos , Distribuição Tecidual
14.
Sci Rep ; 12(1): 1144, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35064184

RESUMO

The classification according to uptake patterns and metabolic parameters on ring-type dedicated breast positron emission tomography (dbPET) is useful for detecting breast cancer. This study investigated the performance of dbPET for incidental findings that were not detected by mammography and ultrasonography. In 1,076 patients with breast cancer who underwent dbPET, 276 findings were incidentally diagnosed before treatment. Each finding was categorized as focus (uptake size ≤ 5 mm), mass (> 5 mm), or non-mass (multiple uptake) according to uptake patterns. Non-mass uptakes were additionally classified based on their distributions as-linear, focal, segmental, regional, or diffuse. Thirty-two findings (11.6%) were malignant and 244 (88.4%) were benign. Visually, 227 (82.3%) findings were foci, 7 (2.5%) were masses, and 42 (15.2%) were non-masses. Malignant rates of focus, mass, and non-mass were 9.7%, 28.6%, and 19.0%, respectively. In the non-mass findings, 23 were regional and diffuse distributions, and presented as benign lesions. Focus uptake with low lesion-to-background ratio (LBR) and no hereditary risk were relatively low (2.7%) in breast cancer. In multivariate analysis, LBR and hereditary risk were significantly associated with breast cancer (p = 0.006 and p = 0.013, respectively). Uptake patterns, LBR, and hereditary risk are useful for predicting breast cancer risk in incidental dbPET findings.


Assuntos
Neoplasias da Mama/epidemiologia , Mama/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Achados Incidentais , Compostos Radiofarmacêuticos/administração & dosagem , Medição de Risco/métodos
15.
Theranostics ; 12(1): 232-259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987643

RESUMO

Theranostics is an emerging paradigm that combines imaging and therapy in order to personalize patient treatment. In nuclear medicine, this is achieved by using radiopharmaceuticals that target identical molecular targets for both imaging (using emitted gamma rays) and radiopharmaceutical therapy (using emitted beta, alpha or Auger-electron particles) for the treatment of various diseases, such as cancer. If the therapeutic radiopharmaceutical cannot be imaged quantitatively, a "theranostic pair" imaging surrogate can be used to predict the absorbed radiation doses from the therapeutic radiopharmaceutical. However, theranostic dosimetry assumes that the pharmacokinetics and biodistributions of both radiopharmaceuticals in the pair are identical or very similar, an assumption that still requires further validation for many theranostic pairs. In this review, we consider both same-element and different-element theranostic pairs and attempt to determine if factors exist which may cause inaccurate dose extrapolations in theranostic dosimetry, either intrinsic (e.g. chemical differences) or extrinsic (e.g. injecting different amounts of each radiopharmaceutical) to the radiopharmaceuticals. We discuss the basis behind theranostic dosimetry and present common theranostic pairs and their therapeutic applications in oncology. We investigate general factors that could create alterations in the behavior of the radiopharmaceuticals or the quantitative accuracy of imaging them. Finally, we attempt to determine if there is evidence showing some specific pairs as suitable for theranostic dosimetry. We show that there are a variety of intrinsic and extrinsic factors which can significantly alter the behavior among pairs of radiopharmaceuticals, even if they belong to the same chemical element. More research is needed to determine the impact of these factors on theranostic dosimetry estimates and on patient outcomes, and how to correctly account for them.


Assuntos
Neoplasias/terapia , Medicina Nuclear/métodos , Cintilografia/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Humanos
16.
Surgery ; 171(1): 55-62, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34340823

RESUMO

BACKGROUND: Primary hyperparathyroidism historically necessitated bilateral neck exploration to remove abnormal parathyroid tissue. Improved localization allows for focused parathyroidectomy with lower complication risks. Recently, positron emission tomography using radiolabeled 18F-fluorocholine demonstrated high accuracy in detecting these lesions, but its cost-effectiveness has not been studied in the United States. METHODS: A decision tree modeled patients who underwent parathyroidectomy for primary hyperparathyroidism using single preoperative localization modalities: (1) positron emission tomography using radiolabeled 18F-fluorocholine, (2) 4-dimensional computed tomography, (3) ultrasound, and (4) sestamibi single photon emission computed tomography (SPECT). All patients underwent either focused parathyroidectomy versus bilateral neck exploration, with associated cost ($) and clinical outcomes measured in quality-adjusted life-years gained. Model parameters were informed by literature review and Medicare costs. Incremental cost-utility ratios were calculated in US dollars/quality-adjusted life-years gained, with a willingness-to-pay threshold set at $100,000/quality-adjusted life-year. One-way, 2-way, and threshold sensitivity analyses were performed. RESULTS: Positron emission tomography using radiolabeled 18F-fluorocholine gained the most quality-adjusted life-years (23.9) and was the costliest ($2,096), with a total treatment cost of $11,245 or $470/quality-adjusted life-year gained. Sestamibi single photon emission computed tomography and ultrasound were dominated strategies. Compared with 4-dimentional computed tomography, the incremental cost-utility ratio for positron emission tomography using radiolabeled 18F-fluorocholine was $91,066/quality-adjusted life-year gained in our base case analysis, which was below the willingness-to-pay threshold. In 1-way sensitivity analysis, the incremental cost-utility ratio was sensitive to test accuracy, positron emission tomography using radiolabeled 18F-fluorocholine price, postoperative complication probabilities, proportion of bilateral neck exploration patients needing overnight hospitalization, and life expectancy. CONCLUSION: Our model elucidates scenarios in which positron emission tomography using radiolabeled 18F-fluorocholine can potentially be a cost-effective imaging option for primary hyperparathyroidism in the United States. Further investigation is needed to determine the maximal cost-effectiveness for positron emission tomography using radiolabeled 18F-fluorocholine in selected populations.


Assuntos
Análise Custo-Benefício/estatística & dados numéricos , Hiperparatireoidismo Primário/diagnóstico , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico , Tomografia por Emissão de Pósitrons/economia , Colina/administração & dosagem , Colina/análogos & derivados , Colina/economia , Radioisótopos de Flúor/administração & dosagem , Radioisótopos de Flúor/economia , Tomografia Computadorizada Quadridimensional/economia , Humanos , Hiperparatireoidismo Primário/economia , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/cirurgia , Medicare/economia , Medicare/estatística & dados numéricos , Modelos Econômicos , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/economia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/economia , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios/economia , Cuidados Pré-Operatórios/métodos , Anos de Vida Ajustados por Qualidade de Vida , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/economia , Sensibilidade e Especificidade , Tecnécio Tc 99m Sestamibi/administração & dosagem , Tecnécio Tc 99m Sestamibi/economia , Ultrassonografia/economia , Estados Unidos
18.
Bioorg Med Chem ; 53: 116525, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34871844

RESUMO

Mutations in isocitrate dehydrogenase 1 (IDH1) are commonly found in various human malignancies. Inhibitors of several mutant IDH1 enzymes have entered clinical trials as target therapeutic drugs for the treatment of patients with IDH1 mutations. Herein, we report the synthesis and evaluation of two 18F-labeled tracers, [18F]AG120 and [18F]AG135 for imaging expression of mutated IDH1 in positron emission tomography (PET). [18F]AG120 and [18F]AG135 were synthesized in decay-corrected radiochemical yield of 1 % and 3 %, respectively, high molar activity (52-66 MBq/nmol and 216-339 MBq/nmol, respectively) and high radiochemical purity (>99%). Both tracers showed good in vitro stability, selective uptake into mutated IDH1-expressing cells and good pharmacokinetic profiles with low uptake in most organs/tissues. Furthermore, [18F]AG120 micro-PET/CT imaging displayed significantly greater uptake in IDH1-mutant than in wild-type tumors, Relatively, uptake of [18F]AG135 was observed neither in IDH1-mutant tumor xenografts nor in wild-type tumors. This study suggests that [18F]AG120 is a promising radiotracer for PET imaging of IDH1 mutation, However, further optimization and investigation are necessary for [18F]AG135 due to the limited uptake in mutated IDH1-expressing tumors.


Assuntos
Inibidores Enzimáticos , Isocitrato Desidrogenase , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Radioisótopos de Flúor , Injeções Subcutâneas , Isocitrato Desidrogenase/antagonistas & inibidores , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacologia , Relação Estrutura-Atividade , Distribuição Tecidual
19.
Biochem Biophys Res Commun ; 587: 58-62, 2022 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-34864547

RESUMO

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/química
20.
J Clin Endocrinol Metab ; 107(3): e1242-e1248, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34643707

RESUMO

CONTEXT: Preoperative localization studies are standard practice in patients undergoing parathyroidectomy for primary hyperparathyroidism (pHPT). The most common modalities are neck ultrasound (US) and sestamibi scanning. However, the nature of pHPT is changing, with imaging increasingly yielding negative results. Numerous studies suggest unlocalized disease is associated with poor outcomes, calling into question whether such patients are best treated conservatively. OBJECTIVE: This study aims to correlate parathyroidectomy outcomes with preoperative imaging in a single, high-volume institution. METHODS: Data from a prospectively maintained departmental database of operations performed from 2017 to 2019 were analyzed. All patients undergoing first-time surgery for sporadic pHPT were included. Data collected included patient demographics, preoperative imaging, surgical strategy, and postoperative outcomes. RESULTS: A total of 609 consecutive parathyroidectomies were included, with a median age of 59 years (range 20-87 years). The all-comer cure rate was 97.5%; this was 97.9% in dual localized patients (those with positive US and sestamibi), compared to 95.8% in the dual unlocalized group (those with negative US and sestamibi) (P = 0.33). Unilateral neck exploration was the chosen approach in 59.9% of patients with double-positive imaging and 5.7% of patients with double-negative imaging (otherwise, bilateral parathyroid visualization was performed). There was no significant difference in postoperative complications between patients undergoing unilateral or bilateral neck exploration. CONCLUSIONS: Patients with negative preoperative imaging who undergo parathyroidectomy are cured in almost 96% of cases, compared to 98% when the disease is localized. This difference does not reach statistical or clinical significance. These findings therefore support current recommendations that all patients with pHPT who are likely to benefit from operative intervention should be considered for parathyroidectomy, irrespective of preoperative imaging findings.


Assuntos
Hiperparatireoidismo Primário/diagnóstico , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico , Paratireoidectomia/estatística & dados numéricos , Tomografia Computadorizada de Emissão de Fóton Único/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisão Clínica , Feminino , Humanos , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/normas , Guias de Prática Clínica como Assunto , Período Pré-Operatório , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Tecnécio Tc 99m Sestamibi/administração & dosagem , Resultado do Tratamento , Ultrassonografia/estatística & dados numéricos , Adulto Jovem
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