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1.
Clin Nucl Med ; 45(3): 195-199, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977481

RESUMO

PURPOSE: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and is exploited for imaging and treatment of patients with prostate cancer. Prostate-specific membrane antigen expression is also demonstrated in the tumor-associated neovasculature endothelium. Juvenile nasal angiofibroma (JNA), being a similar highly vascular tumor, may also demonstrate significant PSMA expression, which may be utilized for its imaging and treatment. METHODS: In this prospective study, 25 clinicoradiologically diagnosed primary JNA patients underwent PSMA PET/CT scan. The scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi (74-111 MBq) of Ga-PSMA-HBED-CC on a dedicated PET/CT scanner. Low-dose CT scan was acquired from vertex to sternoclavicular joint (100 mA, 20 kVp, 3-mm slice thickness, 0.8 pitch). Images were reconstructed with iterative reconstruction technique (4 iterations, 24 subsets). The objective was to assess the intensity and pattern of PSMA uptake in primary JNA patients. RESULTS: All cases (n = 25) of primary JNA showed PSMA expression in the tumor (100%). The median PSMA SUVmax ratio of tumor to background was 4.57 (range, 2.08-7.27). Intracranial extension in 14 of 25 patients was prominently visualized because of absence of background uptake in the brain. Advanced stage tumors demonstrated greater uptake than early tumors (P = 0.011). A statistically nonsignificant trend was noted for decreasing uptake with increasing age after normalizing for stage (Spearman correlation coefficient r = -0.08). CONCLUSIONS: Assessment of PSMA expression in JNA by PSMA PET/CT opens up a new window of opportunity with respect to its radiological staging, vascularity assessment, and molecular characterization. A potential role in identification of the difficult residual-recurrent disease is anticipated and perhaps also in radioligand therapy for residual/recurrent JNA.Clinical Trials Registry of India (CTRI/2018/08/015479).


Assuntos
Angiofibroma/diagnóstico por imagem , Antígenos de Superfície/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Neoplasias Nasais/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Angiofibroma/metabolismo , Antígenos de Superfície/genética , Criança , Ácido Edético/análogos & derivados , Ácido Edético/farmacocinética , Glutamato Carboxipeptidase II/genética , Humanos , Neoplasias Nasais/metabolismo , Oligopeptídeos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Adulto Jovem
2.
Cardiovasc Intervent Radiol ; 43(1): 147-154, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31444628

RESUMO

INTRODUCTION: Precision medicine expands the treatment options for metastatic castration-resistant prostate cancer (mCRPC) by targeting druggable genetic aberrations. Aberrations can be identified following molecular analysis of metastatic tissue. Bone metastases, commonly present in mCRPC, hinder precision medicine due to a high proportion of biopsies with insufficient tumor cells for next-generation DNA sequencing. We aimed to investigate the feasibility of incorporating advanced target planning and needle guidance in bone biopsies and whether this procedure increases biopsy tumor yield and success rate of molecular analysis as compared to the current standards, utilizing only CT guidance. MATERIALS AND METHODS: In a pilot study, ten mCRPC patients received 68Ga-prostate-specific membrane antigen (PSMA)-PET/CT and diffusion-weighted MRI as biopsy planning images. These datasets were fused for targeting metastatic lesions with high tumor densities. Biopsies were performed under cone-beam CT (CBCT) guidance. Feasibility of target planning and needle guidance was assessed, and success of molecular analysis and tumor yield were reported. RESULTS: Fusion target planning and CBCT needle guidance were feasible. Nine out of ten biopsies contained prostate cancer cells, with a median of 39% and 40% tumor cells by two different sequencing techniques. Molecular analysis was successful in eight of ten patients (80%). This exceeds previous reports on CT-guided biopsies that ranged from 33 to 44%. In two patients, important druggable aberrations were found. DISCUSSION: A biopsy procedure using advanced target planning and needle guidance is feasible and can increase the success rate of molecular analysis in bone metastases, thereby having the potential of improving treatment outcome for patients with mCRPC. LEVEL OF EVIDENCE: Level 4, case series.


Assuntos
Neoplasias Ósseas/patologia , Tomografia Computadorizada de Feixe Cônico/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Ácido Edético/análogos & derivados , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Radiografia Intervencionista/métodos , Reprodutibilidade dos Testes
3.
Clin Nucl Med ; 45(1): 11-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31663868

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. After initial therapy and total resection of GBM, 80% to 90% of recurrences occur at the surgical margins. Currently, limited data are available in the literature on the possible use of Ga-prostate-specific membrane antigen (PSMA-11) for diagnosis of recurrence in GBM patients. The aim was to assess the feasibility and potential of Ga-PSMA-11 PET/CT as a diagnostic procedure in patients with histologically confirmed of GBM and suspected recurrent disease on MRI. RESULTS: No radiopharmaceutical-related adverse events were noted. Characterization of recurrent disease with MRI included T2-weighted fast spin-echo images, fluid-attenuated inversion recovery and diffusion-weighted imaging sequences, and gadolinium enhanced T1-weighted images. Visual interpretation of PET showed increased accumulation of Ga-PSMA-11 in recurrent lesion detected by T1 contrast enhanced and diffusion-weighted imaging images in all patients with a median SUVmax of the tumor of 6.5 and an SUVmean of 3.5. The median tumor-to-background brain ratio and tumor-to-liver ratio obtained from Ga-PSMA-11 PET/CT were 96.7 and 0.8, respectively. CONCLUSIONS: The extremely low background uptake in normal brain tissue and consequently high tumor-to-brain ratio make Ga-PSMA-11 PET/CT highly promising for diagnosis of recurrent disease in GBM patients. Although PSMA expression in recurrent GBM also opens a potential way for targeted peptide therapy with α/ß-emitters as well as for prediction of treatment with antiangiogenic agents, the low tumor-to-liver ratio observed in the majority of patients in this study suggests a limited role of radiolabeled PSMA ligands for targeted radionuclide therapy of recurrent GBM.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Ácido Edético/análogos & derivados , Glioblastoma/diagnóstico por imagem , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva
4.
Prostate ; 80(1): 74-82, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31614001

RESUMO

BACKGROUND: To assess which parameters of [68 Ga]Ga-PSMA-11 positron emission tomography (PSMA-PET) predict response to systemic therapies in metastatic (m) castration-resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS). METHODS: We retrospectively assessed the following PSMA-PET parameters in 43 patients before and after systemic therapies for mCRPC: PSMA total tumor volume (TTV), mean standardized uptake value (SUVmean), SUVmax, and SUVpeak. prostate-specific antigen (PSA) levels and PSMA-PET/CT(magnetic resonance imaging [MRI]) imaging were both performed within 8 weeks before and 6 weeks after systemic therapy. PSMA-PET and CT (MRI) images were reviewed according to the modified PET Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results were compared to PSA response. Univariable survival analyses were performed. RESULTS: Overall, 43 patients undergoing 67 systemic therapies were included (9 patients radium-223, 12 cabazitaxel, 22 docetaxel, 6 abiraterone, and 18 enzalutamide). Median serum PSA level before any therapy was 11.3 ng/mL (interquartile range [IQR] = 3.3, 30.1). Delta (d) PSA after systemic therapies was -41%, dTTV 10.5%, dSUVmean -7.5%, dSUVmax -13.3%, dSUVpeak -12%, and dRECIST -13.3%. Overall, 31 patients had dPSA response (46.3%), 12 stable disease (17.9%), and 24 progressive disease (35.8%). All observed PET parameters, as well as the RECIST evaluation, were significantly associated with PSA response (dTTV P = .003, dSUVmean P = .003, dSUVmax P = .011, dSUVpeak P < 0001, dRECIST P = .012), while RECIST assessment was applicable in 37 out of 67 patients (55.2%). Within a median follow-up of 33 months (IQR = 26, 38), 10 patients (23.3%) died of PC. On univariable survival analyses, neither the investigated PET parameters nor PSA level or RECIST criteria were associated with OS. CONCLUSION: PSMA-PET provides reliable parameters for prediction of response to systemic therapies for mCRPC. These parameters, if confirmed, could enhance RECIST criteria, specifically concerning its limitations for sclerotic bone lesions.


Assuntos
Ácido Edético/análogos & derivados , Oligopeptídeos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/terapia , Idoso , Radioisótopos de Gálio , Humanos , Masculino , Metástase Neoplásica , Tomografia por Emissão de Pósitrons/métodos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos , Estudos Retrospectivos
5.
Clin Nucl Med ; 45(1): e51-e52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31246688

RESUMO

A 63-year-old man with elevated prostate-specific antigen serum levels and enlarged prostate gland underwent ultrasound-guided transrectal biopsy, which did not reveal any evidence of malignancy. In order to help guidance of repeat biopsy, Ga-prostate-specific membrane antigen-targeted ligand PET (PSMA PET/CT) was ordered. PET/CT scan showed no abnormal PSMA expression within the prostate gland. There were, however, multiple PSMA-expressing osteolytic lesions throughout the axial skeleton. Bone lesion biopsy obtained for final workup revealed multiple solitary plasmacytomas with multifocal bone involvement. This rare case highlights the utility of PSMA PET/CT in diagnosing nonprostate malignancies.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Ácido Edético/análogos & derivados , Mieloma Múltiplo/diagnóstico por imagem , Oligopeptídeos , Plasmocitoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Biópsia , Neoplasias Ósseas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Plasmocitoma/patologia
6.
Clin Nucl Med ; 45(1): e57-e58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524682

RESUMO

We present a case of a 19-year-old woman with Ewing sarcoma of the iliac bone in whom Ga-PSMA-HBED-CC PET/CT showed high radiotracer activity in the primary tumor. The present case documents the in vivo expression of PSMA in Ewing sarcoma family of tumors and adds on to the list of nonprostatic malignancies showing PSMA expression.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Ácido Edético/análogos & derivados , Fluordesoxiglucose F18 , Radioisótopos de Gálio , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Sarcoma de Ewing/diagnóstico por imagem , Humanos , Masculino , Adulto Jovem
7.
Clin Nucl Med ; 45(1): e39-e40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31693611

RESUMO

The use of PET/CT with prostate-specific membrane antigen radioligands for staging prostate cancer patients presenting a biochemical recurrence is increasing. As a consequence, the number of reports of diagnostic pitfall of this imaging modality is also increasing. A 75-year-old man referred for a second episode of biochemical recurrence of prostate cancer presented an isolated intense prostate-specific membrane antigen-11 uptake from a right lung abnormality. This abnormality was suggestive of pulmonary vein varix on contrast-enhanced lung CT. The uptake remained stable 1 month after starting androgen deprivation therapy, which confirmed the diagnostic of pulmonary vein varix.


Assuntos
Ácido Edético/análogos & derivados , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Veias Pulmonares/diagnóstico por imagem , Varizes/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Metástase Neoplásica
8.
Clin Nucl Med ; 45(1): 19-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789908

RESUMO

PURPOSE: The aim of this study was to evaluate the efficacy and safety of Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). METHODS: In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients. RESULTS: The median age of patients was 66.5 years (range, 30-88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects. CONCLUSIONS: Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.


Assuntos
Dipeptídeos/efeitos adversos , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Dipeptídeos/metabolismo , Ácido Edético/análogos & derivados , Compostos Heterocíclicos com 1 Anel/metabolismo , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
9.
Clin Nucl Med ; 45(1): 81-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31693605

RESUMO

Prostate cancer (PCa) treatment monitoring usually relies on prostate-specific antigen to detect disease progression or relapse. PET/CT with prostate-specific membrane antigen (PSMA) ligands has shown high accuracy in detecting metastatic PCa lesions and could help assess response to therapy. We describe herein the early relapse detection of a hormone-sensitive metastatic upfront PCa treated with docetaxel on Ga-PSMA-11 PET/CT before biochemical progression. PSMA PET/CT should be considered to monitor PCa response to chemotherapy to detect early relapse, regardless of prostate-specific antigen levels, increasing the chances of finding low-volume oligoprogressive disease.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Diagnóstico Precoce , Ácido Edético/análogos & derivados , Humanos , Masculino , Metástase Neoplásica , Oligopeptídeos , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos
10.
Clin Nucl Med ; 45(3): e151-e153, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31876821

RESUMO

Prostate-specific membrane antigen (PSMA) is a transmembrane enzyme also known as folate hydrolase 1 highly expressed by prostate cancer (PCa) cells. However, PSMA overexpression by tumor-associated neovasculature of a variety of solid tumors, including glioblastoma (GBM), has also been proven. This clinical case reports about a 67-year-old man with a history of PCa who underwent radical surgery for GBM and performed a Ga-PSMA-11 PET/CT to restage PCa. PET imaging showed PSMA uptake in GBM residual disease after surgery. This finding suggests a possible role of PSMA inhibitors as diagnostic and therapeutic agents in patients affected by GBM.


Assuntos
Ácido Edético/análogos & derivados , Glioblastoma/diagnóstico por imagem , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Idoso , Progressão da Doença , Humanos , Masculino , Neoplasia Residual , Recidiva
11.
Nucl Med Commun ; 41(1): 11-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31764593

RESUMO

OBJECTIVE: Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [Tc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [Ga]Ga-DOTA-TOC (Somakit-TOC). METHODS: Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (<25 ml). Sorption tests were performed according to the literature. RESULTS: After 2 h storage in a syringe, drug sorption of Tektrotyd and Somakit-TOC was of less than 2.5% and similar to other Tc-radiopharmaceuticals (range: from 1.1 ± 0.5% to 4.2 ± 0.6%). For Tektrotyd, this sorption phenomenon was positively influenced by the drug concentration and a short contact with the medical device (4.8 ± 0.2% up to 5 s vs. 2.3 ± 0.2%, n = 4; P < 0.001). For Somakit-TOC, the duration of contact with syringe had no impact (1.6 ± 0.2% up to 5 s vs. 1.7 ± 0.6%; P = 1.000). No drug radiolysis or alteration of microbiological aspects were observed. No impurity from a 3-piece-syringe was observed according to drug aspect, pH, and subvisible and visible particles, which remained within specification of the current European Pharmacopoeia. CONCLUSION: This study found that drug sorption to packaging was compatible with clinical use and absence of drug alteration of Tektrotyd and Somakit-TOC after repackaging in a syringe in polypropylene and prolonged storage during 2 h.


Assuntos
Administração Intravenosa/instrumentação , Ácido Edético/análogos & derivados , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/química , Contaminação de Medicamentos , Ácido Edético/administração & dosagem , Ácido Edético/química , Ácidos Nicotínicos/química , Octreotida/administração & dosagem , Controle de Qualidade , Seringas/microbiologia
12.
Nuklearmedizin ; 58(6): 443-450, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31724145

RESUMO

AIM: In patients with metastasized castration-resistant prostate cancer a reliable imaging-based therapy response assessment in addition to PSA kinetics is desirable. Recently, measurements of whole-body tumour burden by [68Ga]PSMA-11 PET/CT have been reported for response assessment in oligometastasic patients. The present study investigated the association of PSMA PET derived parameters and serum PSA level before and after [177Lu]PSMA-617 radioligand therapy (RLT). METHODS: This retrospective study assessed whole-body PSMA tumour volume (PSMA-TV) in 10 patients with multifocal to diffuse metastases before and after 2 cycles of RLT using volume of interest (VOI) analysis. A standardized uptake value (SUV) threshold-based approach was used to semi-automatically delineate all voxels with a SUV ≥ 2.0 g/ml using the software ROVER® (ABX Radeberg, Germany). Voxels with physiological tracer uptake (e. g. kidneys) were excluded manually. Correlations between PSMA-TV and serum PSA level before and after two cycles of RLT as well as changes thereof (ΔPSMA-TV and ΔPSA, respectively) were calculated. RESULTS: Changes of ΔPSMA-TV and ΔPSA were concordant in 7 of 10 patients. Whereas a good correlation was found between PSMA-TV and PSA before RLT (ρ = 0.81, p = 0.0049), this correlation was attenuated after RLT (ρ = 0.64, p = 0.0479). Consequently, no association was found between ΔPSMA-TV and ΔPSA (ρ = 0.39, p = 0.26). CONCLUSION: The attenuation of the correlation of PSA and PSMA-TV after RLT suggests that in patients with advanced disease the comparison of imaging based parameters such as PSMA-TV and PSA level might be useful for an adequate monitoring of treatment response.


Assuntos
Dipeptídeos/uso terapêutico , Ácido Edético/análogos & derivados , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Oligopeptídeos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Carga Tumoral , Idoso , Idoso de 80 Anos ou mais , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento
13.
Breast Cancer Res ; 21(1): 116, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640747

RESUMO

BACKGROUND: Triple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT). METHODS: Tube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy. A binding study with 68Ga-labeled PSMA-addressing ligand was used to indicate targeting potential of PSMA on tumor-conditioned HUVEC cells. For mimicking of the therapeutic application, tube formation potential and vitality of tumor-conditioned HUVEC cells were assessed following an incubation with radiolabeled PSMA-addressing ligand [177Lu]-PSMA-617. For in vivo experiments, NUDE mice were xenografted with triple-negative breast cancer cells MDA-MB231 or estrogen receptor expressing breast cancer cells MCF-7. Biodistribution and binding behavior of [68Ga]-PSMA-11 was investigated in both tumor models at 30 min post injection using µPET. PSMA- and CD31-specific staining was conducted to visualize PSMA expression and neovascularization in tumor tissue ex vivo. RESULTS: The triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of PSMA was efficiently addressed by radiolabeled PSMA-specific ligands. 177Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. In vivo, as visualized by µPET, radiolabeled PSMA-ligand accumulated specifically in the triple-negative breast cancer xenograft MDA-MB231 (T/B ratio of 43.3 ± 0.9), while no [68Ga]-PSMA-11 was detected in the estrogen-sensitive MCF-7 xenograft (T/B ratio of 1.1 ± 0.1). An ex vivo immunofluorescence analysis confirmed the localization of PSMA on MDA-MB231 xenograft-associated endothelial cells and also on TNBC cells. CONCLUSIONS: Here we demonstrate PSMA as promising target for two-compartment endogenous radio-ligand therapy of triple-negative breast cancer.


Assuntos
Radioisótopos de Gálio/uso terapêutico , Glutamato Carboxipeptidase II/antagonistas & inibidores , Lutécio/uso terapêutico , Radioisótopos/uso terapêutico , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Antígenos de Superfície/metabolismo , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiologia , Vasos Sanguíneos/efeitos da radiação , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Dipeptídeos/metabolismo , Dipeptídeos/uso terapêutico , Ácido Edético/análogos & derivados , Ácido Edético/metabolismo , Ácido Edético/uso terapêutico , Glutamato Carboxipeptidase II/metabolismo , Compostos Heterocíclicos com 1 Anel/metabolismo , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Humanos , Ligantes , Células MCF-7 , Camundongos Nus , Oligopeptídeos/metabolismo , Oligopeptídeos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
17.
Radiology ; 293(2): 350-358, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31502937

RESUMO

Background Recent studies have reported the additive value of combined gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (hereafter called 68Ga-PSMA-11) PET/MRI for the detection and localization of primary prostate cancer compared with multiparametric MRI. Purpose To compare the diagnostic accuracy and interrater agreement of multiparametric MRI and 68Ga-PSMA-11 PET/MRI for the detection of extracapsular extension (ECE) and seminal vesicle infiltration (SVI) in patients with prostate cancer. Materials and Methods Retrospective analysis of 40 consecutive men who underwent multiparametric MRI and 68Ga-PSMA-11 PET/MRI within 6 months for suspected prostate cancer followed by radical prostatectomy between April 2016 and July 2018. Four readers blinded to clinical and histopathologic findings rated the probability of ECE and SVI at multiparametric MRI and PET/MRI by using a five-point Likert-type scale. The prostatectomy specimen served as the reference standard. Accuracy was assessed with a multireader multicase analysis and by calculating reader-average areas under the receiver operating characteristics curve (AUCs), sensitivity, and specificity for ordinal and dichotomized data in a region-specific and patient-specific approach. Interrater agreement was assessed with the Fleiss multirater κ. Results For multiparametric MRI versus PET/MRI in ECE detection, respectively, AUC, sensitivity, and specificity in the region-specific analysis were 0.67 and 0.75 (P = .07), 28% (21 of 76) and 47% (36 of 76) (P = .09), and 94% (529 of 564) and 90% (509 of 564) (P = .007). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.66 and 0.73 (P = .19), 46% (22 of 48) and 69% (33 of 48) (P = .04), and 75% (84 of 112) and 67% (75 of 112) (P = .19), respectively. For multiparametric MRI versus PET/MRI in SVI detection, respectively, AUC, sensitivity, and specificity of the region-specific analysis were 0.66 and 0.74 (P = .21), 35% (seven of 20) and 50% (10 of 20) (P = .25), and 98% (295 of 300) and 94% (282 of 300) (P < .001). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.65 and 0.79 (P = .25), 35% (seven of 20) and 55% (11 of 20) (P = .20), and 98% (137 of 140) and 94% (131 of 140) (P = .07), respectively. Interrater reliability for multiparametric MRI versus PET/MRI did not differ for ECE (κ, 0.46 vs 0.40; P = .24) and SVI (κ, 0.23 vs 0.33; P = .39). Conclusion Our results suggest that gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (68Ga-PSMA-11) PET/MRI and multiparametric MRI perform similarly for local staging of prostate cancer in patients with intermediate-to-high-risk prostate cancer. The increased sensitivity of 68Ga-PSMA-11 PET/MRI for the detection of extracapsular disease comes at the cost of a slightly reduced specificity. © RSNA, 2019.


Assuntos
Imagem Multimodal , Invasividade Neoplásica/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Glândulas Seminais/diagnóstico por imagem , Idoso , Ácido Edético/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Oligopeptídeos , Tomografia por Emissão de Pósitrons , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Compostos Radiofarmacêuticos , Glândulas Seminais/patologia , Sensibilidade e Especificidade
18.
Colloids Surf B Biointerfaces ; 183: 110452, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473409

RESUMO

Currently used Gd-based and Mn-based small molecular MRI contrast agents fail to meet the requirements for the long-term monitoring, and the potential safety risk under high administration dose or repeat dosing needs to be considered. In the present study, a biocompatible macromolecular magnetic resonance imaging (MRI) contrast agents based on O-carboxymethyl chitosan (CMCS), CMCS-(Mn-DTPA)n was designed and synthesized. The relaxivity of CMCS-(Mn-DTPA)n is approximately 3.5 and 5.5 times higher than that of Gd-DTPA and Mn-DPDP in aqueous solution, respectively. The MRI signal intensity in the kidney and liver of Sprague Dawley (SD) rats is significantly increased at a dose of 0.03 mM Mn/kg b.w. CMCS-(Mn-DTPA)n accompanied by a long effective imaging window. According to in vitro studies, CMCS-(Mn-DTPA)n exhibits good cellular and blood biocompatibility at the dose necessary for MRI imaging. Based on the results from in vivo studies, manganese (Mn) is completely excreted from SD rats within ten days after administration and does not exert a pathological effect on the liver. CMCS-(Mn-DTPA)n represents a potentially novel MRI contrast agent due to its excellent relaxivity, long effective imaging window and good biocompatibility.


Assuntos
Quitosana/análogos & derivados , Meios de Contraste/química , Imagem por Ressonância Magnética/métodos , Manganês/química , Animais , Quelantes/química , Quitosana/química , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Ácido Edético/análogos & derivados , Ácido Edético/química , Gadolínio DTPA/química , Rim/diagnóstico por imagem , Rim/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/química , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
20.
Nucl Med Commun ; 40(11): 1105-1111, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31469805

RESUMO

OBJECTIVES: Recent reports warn against erroneous mistaking of celiac and stellate sympathetic ganglia for metastatic lymph nodes on multimodal prostate-specific membrane antigen (PSMA)-ligand PET imaging. The aim was to check the intensity of Ga-PSMA-11 uptake and magnetic resonance (MR) features of superior cervical ganglia (SCG) on PET/MR imaging. METHODS: In 89 patients 106 SCG were reliably identified on Ga-PSMA-11 PET/MR. For each SCG, qualitative assessment (visual subjective avidity, diffusion restriction, shape, and the presence of central hypointensity) and quantitative measurements [dimensions, maximal standardized uptake value (SUVmax), mean apparent diffusion coefficient (ADC)] were performed. RESULTS: Mean SUVmax in SCG amounted to 1.88 ± 0.63 (range: 0.87-4.42), with considerable metabolic activity (SUVmax ≥ 2) in 37.7% of SCG; mean thickness was 3.18 ± 1.08 mm. In subjective visual evaluation, SCG avidity was classified as mistakable or potentially mistakable with underlying malignancy in 32.1% of cases. Mean ADC values amounted 1749.83 ± 428.83 × 10mm/s. In visual assessment, 74.5% of ganglia showed moderate to high diffusion restriction. An oval or longitudinal shape on transverse MR plane was presented by 59.4% of SCG. The central hypointensity was detected on MR T2-weighted images only in 10.4% of SCG. CONCLUSION: SCG, similar to other sympathetic ganglia, show Ga-PSMA-11 uptake. SCG avidity may be of significance, especially in view of frequently occurring SCG oval or longitudinal shape, and moderate to high diffusion restriction in visual assessment, potentially suggesting malignancy on transverse MR plane. Diagnostic imaging specialists and clinicians should be aware of the above.


Assuntos
Ácido Edético/análogos & derivados , Imagem por Ressonância Magnética , Imagem Multimodal , Oligopeptídeos , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Gânglio Cervical Superior/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Erros de Diagnóstico/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imagem Corporal Total
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