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1.
Chem Biol Drug Des ; 104(1): e14578, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-39044291

RÉSUMÉ

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista-galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99mTc. Herein we present a shorter analogue which also preserves the γ-core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through a lysine linker in the amino-terminal group (NOTA-KGHCRGFRRRC) and radiolabelled with 68Ga ([68Ga]Ga-NOTA-K-EcgDf1(10)). The [68Ga]Ga-NOTA-K-EcgDf1(10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [68Ga]Ga-NOTA-K-EcgDf1(10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non-target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively.


Sujet(s)
Défensines , Radio-isotopes du gallium , Tomographie par émission de positons , Radiopharmaceutiques , Animaux , Humains , Souris , Séquence d'acides aminés , Défensines/composition chimique , Radio-isotopes du gallium/composition chimique , Peptides/composition chimique , Tomographie par émission de positons/méthodes , Radiopharmaceutiques/composition chimique , Distribution tissulaire , Composés organiques du technétium/composition chimique
2.
Radiother Oncol ; 190: 109975, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-37913955

RÉSUMÉ

INTRODUCTION: Radiotracer 68Ga-PSMA-11 used in PET/CT scans allows for identification and localization of gland tissue. It allows for their consideration in clinical scenarios and to design further and stronger research to answer pertinent questions regarding their function and implications. We aimed to externally validate first reported findings of location, size, and ligand uptake of the tubarial glands using 68Ga-PSMA-11 PET/CT. MATERIALS AND METHODS: A cross-sectional study was performed with 68Ga-PSMA-11 PET/CT studies of patients with prostate cancer confirmed diagnosis from the database of the Radiology Department from 2018 to 2022. The maximum cephalocaudal length (CCL) in the tubarial glands and the Maximum Standardized Uptake Value (SUVmax) of major glands were recorded. RESULTS: A total of 202 patients were included (mean age 67.43 ± 8.5). The mean CCL of the tubarial glands was 37.38 ± 9.84 and a SUVmax of 6.56 ± 2.14. The rest of the glands were as follows: parotid 15.12 ± 4.43, submandibular 16.82 ± 5.43 and sublingual 5.84 ± 3.24. No differences were found between laterality. A weak correlation between age and SUVmax of tubarial glands was identified. Tubarial glands had a similar 68Ga-PSMA-11 uptake to that of sublingual glands. CONCLUSION: This study corroborates the existence of a conglomerate of glands in the nasopharynx roof, near the posterolateral pharyngeal recess. It serves as validation in a different population with similar results in previous research. Without 68GA-PSMA-11 PET/CT the abundance, configuration and potential clinical relevance of these glands would probably not have been identified. Radiotracer uptake was similar amongst the major salivary glands, with a more similar uptake to that shown by the sublingual gland.


Sujet(s)
Isotopes du gallium , Radio-isotopes du gallium , Tumeurs de la prostate , Mâle , Humains , Adulte d'âge moyen , Sujet âgé , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Études transversales , Tumeurs de la prostate/imagerie diagnostique
3.
J Nucl Cardiol ; 30(6): 2702-2711, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37605061

RÉSUMÉ

BACKGROUND: Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD. METHODS AND RESULTS: Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed 18F-FDG and 68Ga-DOTATOC uptake, 68Ga-DOTATOC corrected SUVmax was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%). CONCLUSION: 18F-FDG and 68Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and 68Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications.


Sujet(s)
Maladie de Chagas , Cardiopathies , Myocardite , Humains , Tomographie par émission de positons couplée à la tomodensitométrie , Fluorodésoxyglucose F18 , Tomographie par émission de positons/méthodes , Radio-isotopes du gallium , Études transversales , Parasitémie , Études prospectives , Myocardite/imagerie diagnostique , Troubles du rythme cardiaque/imagerie diagnostique , Inflammation/imagerie diagnostique , Mort subite cardiaque , Maladie de Chagas/complications , Maladie de Chagas/imagerie diagnostique
4.
Ann Surg Oncol ; 30(7): 4550-4551, 2023 Jul.
Article de Anglais | MEDLINE | ID: mdl-37010662

RÉSUMÉ

Prostate cancer (PCa) is the second most common malignant tumor in men in Brazil and worldwide. Although positron emission tomography (PET) prostate-specific membrane antigen (PSMA) has been used for over 10 years and several studies have been published regarding its superior performance in PCa primary staging and other scenarios, the management decision is often still based on conventional imaging information. A retrospective analysis was performed in 35 patients with PCa in the primary staging scenario with conventional exams as well as with PET PSMA. The findings of our study showed changes on the staging classification and significant impact on the therapeutic choice. PET PSMA is a dependable imaging exam and has already proved its worth and superiority when compared with conventional methods to evaluate PCa patients in primary staging and biochemical relapse, in addition to other potential roles. Prospective studies are needed to assess the outcome of patients whose management was guided by PSMA.


Sujet(s)
Tomographie par émission de positons couplée à la tomodensitométrie , Tumeurs de la prostate , Mâle , Humains , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Études rétrospectives , Récidive tumorale locale/imagerie diagnostique , Récidive tumorale locale/anatomopathologie , Tomographie par émission de positons/méthodes , Tumeurs de la prostate/anatomopathologie , Stadification tumorale , Radio-isotopes du gallium
5.
Ann Surg Oncol ; 30(7): 4541-4549, 2023 Jul.
Article de Anglais | MEDLINE | ID: mdl-36995451

RÉSUMÉ

BACKGROUND: Prostate cancer (PCa) is the most common malignant tumor in males and conventional imaging does not provide accurate primary staging. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) presents superior performance and strongly affects therapeutic choice. OBJECTIVE: The aim of this study was to evaluate the impact of PSMA PET, compared with conventional imaging methods, on the therapeutic approach in primary staging scenarios in patients with PCa treated at the Brazilian National Public Health System. METHODS: Overall, 35 patients diagnosed with PCa were evaluated using PSMA after conventional staging imaging with multiparametric magnetic resonance (MMR) and/or total abdominal computed tomography (CT) scan and bone scintigraphy (BS). The PCa extension identified by PET was compared with conventional imaging; staging changes and the management impact were then determined. PET comparison with conventional imaging, staging, and decision-making changes was analyzed using descriptive statistics. RESULTS: PET revealed local disease (LD) in 15 (42.9%) patients, seminal vesicle invasion (SVI) in 5 (14.3%) patients, pelvic nodal impairment (PNI) in 7 (20%) patients, pelvic and distant nodes in 3 (8.6%) patients, pelvic nodes and bone metastasis in 4 (11.4%) patients, and pelvic and distant nodes and bone metastasis in 1 (2.8%) patient. Staging changes were observed in 60% of patients, with downstaging predominance (76.2%). Volume increase was identified in 11 (31.4%) patients (only 4 related to upstaging, 36.4%). The board changed management decisions for 60% of the patients. The main limitations of this study were the sample size and its retrospective nature. CONCLUSIONS: PSMA findings changed the management decisions in more than half of the patients, which made the majority eligible for locoregional treatment and avoided unnecessary procedures in the systemic disease scenario.


Sujet(s)
Antigènes de surface , Carcinomes , Glutamate carboxypeptidase II , Tumeurs de la prostate , Humains , Mâle , Brésil/épidémiologie , Carcinomes/imagerie diagnostique , Carcinomes/anatomopathologie , Carcinomes/thérapie , Radio-isotopes du gallium , Stadification tumorale , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Prostate/anatomopathologie , Tumeurs de la prostate/imagerie diagnostique , Tumeurs de la prostate/thérapie , Tumeurs de la prostate/anatomopathologie , Santé publique , Études rétrospectives
6.
Eur J Nucl Med Mol Imaging ; 50(8): 2432-2440, 2023 07.
Article de Anglais | MEDLINE | ID: mdl-36988710

RÉSUMÉ

PURPOSE: The aim of this study was to compare [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT image findings in patients with multiple myeloma (MM). METHODS: Twenty consecutive patients with symptomatic biopsy-proven MM were submitted to whole body [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT with a time interval of 1-8 days between procedures. All lesions were counted and had their maximum SUV (SUVmax) measured. Intra-class correlation (ICC) was used to assess the agreement between [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT findings. RESULTS: A total of 266 lesions were detected in 19/20 patients. [18F]FDG detected 223/266 (84%) lesions in 17 patients and [68Ga]Ga-PSMA-11 190/266 (71%) lesions in 19 patients. Both procedures did not identify any active lesion in 1 patient. Forty-three (16%) lesions were detected only by [68Ga]Ga-PSMA-11 and 76 (29%) only by [18F]FDG. Both tracers identified 147 (55%) lesions. Intralesional mismatch of FDG-PSMA uptake was identified in 25 of these 147 lesions, found in 8 different patients. Different lesions with uptake of only [18F]FDG or [68Ga]Ga-PSMA-11 in the same patient were found in 4 patients. The highest SUVmax of [18F]FDG and [68Ga]Ga-PSMA-11 had a median (min-max) SUVmax of 6.5 (2.0-37.8) and 5.5 (1.7-51.3), respectively. [18F]FDG and [68Ga]Ga-PSMA-11 respectively identified 18 and 19 soft tissue lesions. False-positive [18F]FDG findings had minimal or no uptake of [68Ga]Ga-PSMA-11. Good reliability (ICC ≥ 0.75) was found for number of lesions, number of soft tissue lesions and highest SUVmax in each patient. CONCLUSION: [18F]FDG or [68Ga]Ga-PSMA-11 alone can detect most MM lesions. Almost half of the lesions take up only one of the tracers, reflecting increased glycolysis or angiogenesis in specific lesions, and suggesting their possible complementary role in MM. The marked [68Ga]Ga-PSMA-11 uptake in some cases raises the possibility of a theranostic approach in selected patients.


Sujet(s)
Radio-isotopes du gallium , Myélome multiple , Humains , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Fluorodésoxyglucose F18 , Myélome multiple/imagerie diagnostique , Reproductibilité des résultats
8.
Einstein (Sao Paulo) ; 20: eAO6599, 2022.
Article de Anglais | MEDLINE | ID: mdl-35584444

RÉSUMÉ

OBJECTIVE: To evaluate the predictive value of positron emission computed tomography or magnetic resonance (PET-CT and PET-MRI) using gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA) in lymph node involvement in prostate cancer. METHODS: A retrospective study comprising 91 patients diagnosed with prostate cancer between 2016 to 2020, who underwent 68Ga-PSMA PET-CT or PET-MRI for staging before prostatectomy. The patients were divided into Group 1, with 65 patients with satisfactory pathological lymph node analysis, and Group 2, with 91 patients representing the sum of patients with pathological lymph node analysis and those with postoperative prostate-specific antigen within 60 days after surgery. Receiver Operating Characteristic curves were used to assess accuracy of predictive capacity of imaging exams for lymph node involvement. RESULTS: Regarding local clinical staging, the groups showed similar results, and 50% were classified as staging T2a. The accuracy of 68Ga-PSMA PET-CT for prostate cancer lymph node staging was 86.5% (95%CI 0.74-0.94; p=0.06), with a sensitivity of 58.3% and specificity of 95%. The accuracy of 68Ga-PSMA PET-MRI was 84.6% (95%CI 0.69-0.94; p=0.09), with a sensitivity of 40% and specificity of 100%. Considering both 68Ga-PSMA PET-CT and PET-MRI, the accuracy was 85.7% (95%CI 0.76-0.92; p=0.015), with sensitivity of 50% and specificity of 97%. CONCLUSION: The imaging tests 68Ga-PSMA PET-CT and PET-MRI were highly accurate to detect preoperative lymph node involvement, and could be useful tools to indicate the need for extended lymph node dissection during radical prostatectomy.


Sujet(s)
Tomographie par émission de positons couplée à la tomodensitométrie , Tumeurs de la prostate , Isotopes du gallium , Radio-isotopes du gallium , Humains , Noeuds lymphatiques/anatomopathologie , Métastase lymphatique/imagerie diagnostique , Métastase lymphatique/anatomopathologie , Imagerie par résonance magnétique , Mâle , Stadification tumorale , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Tomographie par émission de positons , Prostatectomie , Tumeurs de la prostate/imagerie diagnostique , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/chirurgie , Études rétrospectives
9.
Arch Endocrinol Metab ; 66(2): 269-271, 2022 Apr 28.
Article de Anglais | MEDLINE | ID: mdl-35315988

RÉSUMÉ

A 59-year-old woman with follicular thyroid carcinoma underwent total thyroidectomy followed by radioiodine treatment. Following treatment, the whole-body scan did not show any abnormal radioiodine uptake. However, during the follow-up, the serum thyroglobulin (Tg) value increased without detectable thyroglobulin-antibodies. We performed a Ga-68 DOTA-TATE PET/CT showing a sternal lesion and several lung nodules with high somatostatin receptor density. Also, on the next day, FDG PET/CT was performed, which confirmed the findings. Considering the high levels of somatostatin receptor expression in such metastases, we planned lu177 DOTA-TATE therapy. After two cycles of lu177 DOTA-TATE injection, serum thyroglobulin significantly dropped, and she claimed that her sternal pain and dyspnea were much better. This was the case of a patient suffering from iodine-refractory follicular thyroid carcinoma, with somatostatin-receptor expression, treated with 177Lu-DOTA-TATE, showing a significant response.


Sujet(s)
Adénocarcinome folliculaire , Tumeurs de la thyroïde , Femelle , Radio-isotopes du gallium , Composés hétéromonocycliques , Humains , Radio-isotopes de l'iode/usage thérapeutique , Adulte d'âge moyen , Tomographie par émission de positons couplée à la tomodensitométrie , Tomographie par émission de positons , Radiopharmaceutiques/usage thérapeutique , Récepteur somatostatine , Thyroglobuline , Tumeurs de la thyroïde/anatomopathologie , Tumeurs de la thyroïde/radiothérapie
10.
Appl Radiat Isot ; 183: 110104, 2022 May.
Article de Anglais | MEDLINE | ID: mdl-35245862

RÉSUMÉ

The study identified occupational exposure in the work of radiology technologists with 68Ga radiopharmaceuticals, in a Nuclear Medicine service in southern Brazil, by means of observation and document analysis. The occupational exposure related the factors, distance, time and shielding. Thus, it was observed high times during handling of the material, small distances between sources and radiosensitive structures, such as the eye lens and the thyroid gland. It is recommended to reassess and standardize the work, once that critical moments should not be restricted only to dosimetric reading.


Sujet(s)
Radio-isotopes du gallium , Exposition professionnelle , Exposition aux rayonnements , Radiopharmaceutiques , Auxiliaires de santé , Brésil , Radio-isotopes du gallium/effets indésirables , Humains , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Radioprotection/normes , Radiopharmaceutiques/effets indésirables , Lieu de travail
11.
Curr Radiopharm ; 15(3): 228-235, 2022.
Article de Anglais | MEDLINE | ID: mdl-35209836

RÉSUMÉ

BACKGROUND: This work aims to present a nuclear medicine imaging service's data regarding applying positron emission-computing tomography (PET/CT) scans with the radiopharmaceutical 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) to diagnose prostate cancer clinical relapse. METHODS: Eighty patients with a mean age of 68.26 years and an average prostatic-specific antigen blood level of 7.49 ng/ml (lower concentration = 0.17 ng/ml) received 68Ga-PSMA-11 intravenously, and full-body images of PET-CT scan were obtained. Of the total of patients admitted to the imaging service, 87.5% were examined for disease's biochemical recurrence and clinical relapse, and 70.0% had a previous radical prostatectomy (RP). RESULTS: Of the patients without RP, 95.8% were detected with intra-glandular disease. The 68Ga- PSMA-11 PET/CT imaging results revealed small lesions, even in patients with low blood levels of prostatic-specific antigen, mainly in metastatic cancer cases in lymph nodes and bones. CONCLUSION: The 68Ga-PSMA-11 PET/CT imaging was essential in detecting prostate cancer, with significantly high sensitivity in detecting recurrent cases. Due to its inherent reliability and sensitivity, PET/CT scanning with 68Ga-PSMA-11 received an increasing number of medical requests throughout the present follow-up study, confirming the augmented demand for this clinical imaging procedure in the regional medical community.


Sujet(s)
Radio-isotopes du gallium , Tumeurs de la prostate , Sujet âgé , Études de suivi , Isotopes du gallium , Humains , Mâle , Récidive tumorale locale/imagerie diagnostique , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Tumeurs de la prostate/anatomopathologie , Radiopharmaceutiques , Reproductibilité des résultats
12.
Urol Oncol ; 40(3): 104.e17-104.e21, 2022 03.
Article de Anglais | MEDLINE | ID: mdl-34911650

RÉSUMÉ

PURPOSE: The aim of this study is to assess the accuracy of the 68Ga-PSMA PET/CT for lymph nodes and bones in the primary stage of prostate cancer. METHODS: A total of 126 patients who were submitted to 68Ga-PSMA PET/CT from January 2016 to February 2019 for prostate cancer staging, detection of clinically significant lesions or active surveillance were included in this study. All studies were read by 2 experienced physicians (a nuclear physician and a radiologist). The reports were made in consensus and used by one of the authors to classify the exam in positive or negative. We evaluated presence of abnormal uptake in the prostate, lymph nodes, and bone. The reference standards were histopathological confirmation, confirmatory imaging exams and/or clinical follow-up showing lesion(s) regression after specific treatment, or typical osseous metastatic lesions and highly increased PSA levels. RESULTS: Measurement of diagnostic performance indicated a sensitivity, specificity and accuracy of 75%, 96.3%, and 90.8%, respectively, for lymph node involvement, and 90.9%, 50%, and 76.5%, respectively for metastatic bone lesions. CONCLUSION: This study showed high specificity and accuracy of 68Ga-PSMA PET/CT for lymph node and bone involvement in prostate cancer staging.


Sujet(s)
Tomographie par émission de positons couplée à la tomodensitométrie , Tumeurs de la prostate , Isotopes du gallium , Radio-isotopes du gallium , Humains , Noeuds lymphatiques/imagerie diagnostique , Noeuds lymphatiques/anatomopathologie , Mâle , Stadification tumorale , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Tumeurs de la prostate/anatomopathologie
13.
Clin Nucl Med ; 47(2): e120-e122, 2022 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-34115708

RÉSUMÉ

ABSTRACT: 18F-prostate-specific membrane antigen (PSMA) 1007 is one of the most promising radiotracers for PET imaging in prostate cancer, minimal urinary clearance, and higher spatial resolution, which are the most outstanding features. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. We present images of metastatic prostate cancer in two patients, where 64Cu-PSMA PET/CT was performed one day after 18F-PSMA-1007 PET/CT. In the two patients, both radiotracers provided high image quality and a similar range of detection for metastatic lesions.


Sujet(s)
Radio-isotopes du cuivre , Tumeurs de la prostate , Radio-isotopes du gallium , Humains , Mâle , Nicotinamide/analogues et dérivés , Oligopeptides , Tomographie par émission de positons couplée à la tomodensitométrie
14.
Int Braz J Urol ; 48(6): 891-902, 2022.
Article de Anglais | MEDLINE | ID: mdl-34003611

RÉSUMÉ

OBJECTIVE: To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer. MATERIALS AND METHODS: Embase, PubMed and Cochrane Library databases were searched for studies published before July 2020. The studies that used 68Ga-PSMA PET/CT for detecting primary prostate cancer, and pathological biopsy as the reference standard were included. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). The quality of enrolled studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: According to our search strategy, 9 studies were included for analysis. A total of 547 patients with primary prostate cancer and 443 lesion segments that underwent 68Ga-PSMA PET/CT scans were included and their pathological biopsies were compared. The results of these studies showed some differences. For instance, the lowest sensitivity of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer was 67%, while the highest sensitivity recorded was 97%. CONCLUSIONS: Compared with conventional imaging examinations, 68Ga-PSMA PET/CT had higher sensitivity and specificity in detecting primary prostate cancer. At present, most of the studies that used 68Ga-PSMA PET/CT for detecting prostate cancer are retrospective studies. Based on its advantage of high detection rate, the use of 68Ga-PSMA PET/CT in the detection of primary prostate cancer is worthy of promotion.


Sujet(s)
Tomographie par émission de positons couplée à la tomodensitométrie , Tumeurs de la prostate , Acide édétique , Isotopes du gallium , Radio-isotopes du gallium , Humains , Ligands , Mâle , Oligopeptides , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Prostate/imagerie diagnostique , Prostate/anatomopathologie , Tumeurs de la prostate/imagerie diagnostique , Tumeurs de la prostate/anatomopathologie , Études rétrospectives
15.
Chem Biol Drug Des ; 98(1): 182-191, 2021 07.
Article de Anglais | MEDLINE | ID: mdl-33982434

RÉSUMÉ

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.


Sujet(s)
Tumeurs du sein/imagerie diagnostique , Radio-isotopes du gallium/composition chimique , Neuropeptide Y/composition chimique , Radiopharmaceutiques/composition chimique , Amines/composition chimique , Séquence d'acides aminés , Animaux , Transport biologique , Radiocinématographie , Femelle , Humains , Lysine/composition chimique , Souris nude , Tumeurs expérimentales , Neuropeptide Y/sang , Neuropeptide Y/pharmacocinétique , Neuropeptide Y/urine , Liaison aux protéines , Radiopharmaceutiques/sang , Radiopharmaceutiques/pharmacocinétique , Radiopharmaceutiques/urine , Coloration et marquage , Relation structure-activité , Distribution tissulaire
16.
Nucl Med Biol ; 96-97: 54-60, 2021.
Article de Anglais | MEDLINE | ID: mdl-33831746

RÉSUMÉ

BACKGROUND: The prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPR) are overexpressed in prostate cancer (PCa). In preclinical studies, the iPSMA-Lys3-Bombesin (iPSMA-BN) heterodimeric ligand has shown a suitable affinity for PSMA and GRPR. This research aimed to assess the biokinetics and radiation dosimetry of [68Ga]Ga-iPSMA-BN in four healthy volunteers based on biodistribution data obtained from whole-body PET/CT studies, as well as to visualize the [68Ga]Ga-iPSMA-BN tumor uptake in a patient with PCa. METHODS: PET/CT images acquired at 5 min, 0.5, 1, and 2 h after radiotracer administration (124.5 ± 2.1 MBq) were corrected for attenuation, scattering, dead-time, and decay. The activity in the segmented volumes of interest (VOIs) in each source organ at different times was adjusted to mono- and bi-exponential biokinetic models (A(t)VOI), from which the total disintegrations (N) were calculated to assess the internal radiation doses by using the OLINDA V1.1 code. RESULTS: Images from the patient showed an evident uptake by the metastasis (SUVmax of 4.7) and by the organs expressing GRPR (pancreas) and PSMA (salivary glands). The average effective dose was 2.70 ± 0.05 mSv, which was like those known for most of the 68Ga studies, making [68Ga]Ga-iPSMA-BN a promising dual-target PET imaging radiotracer for PCa. CONCLUSIONS: [68Ga]Ga-iPSMA-BN, capable of detecting both PSMA and GRPR with suitable biokinetics and dosimetric patterns, could be a potential complementary diagnostic tool for the improvement of prostate cancer PET imaging.


Sujet(s)
Radio-isotopes du gallium , Tomographie par émission de positons couplée à la tomodensitométrie , Bombésine , Récepteur bombésine , Distribution tissulaire
17.
Eur J Nucl Med Mol Imaging ; 48(9): 2925-2934, 2021 08.
Article de Anglais | MEDLINE | ID: mdl-33543325

RÉSUMÉ

PURPOSE: To evaluate the performance of [68Ga]Ga-PSMA-11 PET/CT in the diagnosis of recurrent prostate cancer (PC) after prostatectomy in a large multicentre cohort. METHODS: The centres, which contributed to this study, were the departments of nuclear medicine of Heidelberg (Germany), Technical University of Munich (Germany) and Albert Einstein Hospital of São Paulo (Brazil). A total of 2533 patients who were scanned with [68Ga]Ga-PSMA-11 PET/CT at 1 h p.i. due to recurrent PC after prostatectomy were included in this retrospective analysis. Exclusion criteria were as follows: patients with untreated primary tumour, previous chemotherapy or Xofigo®; those previously treated with exclusively external beam radiation therapy or HIFU; those referred for PSMA-therapy; and those treated with ADT (including first- and second-generation ADT) within the last 6 months. Potential influences of different factors such as PSA level, PSA doubling-time (PSADT), PSA velocity (PSAVel), Gleason Score (GSC, including the separate analysis of 7a and 7b), age and amount of injected tracer were evaluated in a multivariable analysis. RESULTS: The rate of pathologic PET/CT-scans was 43% for PSA ≤ 0.2 ng/ml, 58% for PSA > 0.2 to ≤ 0.5, 72% for PSA > 0.5 to ≤ 1.0 and increased to a maximum of 93% for PSA > 10 ng/ml. A pathological PET/CT was significantly (p = 0.001) associated with PSA level and higher GSC. Amount of injected tracer, age, PSADT and PSAVel were not associated with a higher probability of a pathological scan. CONCLUSION: [68Ga]Ga-PSMA-11 PET/CT at 1 h p.i. confirmed its high performance in the largest patient cohort yet analysed. Tumour detection showed a clear association with higher PSA and higher GSC. No association was found between a pathological [68Ga]Ga-PSMA-11 PET/CT and age, amount of injected tracer, PSADT or PSAVel.


Sujet(s)
Tomographie par émission de positons couplée à la tomodensitométrie , Tumeurs de la prostate , Brésil , Acide édétique , Radio-isotopes du gallium , Allemagne , Humains , Mâle , Récidive tumorale locale/imagerie diagnostique , Antigène spécifique de la prostate , Prostatectomie , Tumeurs de la prostate/imagerie diagnostique , Tumeurs de la prostate/chirurgie , Études rétrospectives
18.
Front Endocrinol (Lausanne) ; 12: 794759, 2021.
Article de Anglais | MEDLINE | ID: mdl-35002972

RÉSUMÉ

Introduction: Thyroid cancer is the main endocrine neoplasia worldwide, for which 131I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of 123I or 124I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes. Methods: We retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic 131I dose whole body scan (WBS) and complementary SPECT/CT, as well as 68Ga-PSMA-11 PET/CT. Results: Ten patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. 68Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas 131I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 - 0.91), as opposed to 131 I (κ = 0.86; 95% CI, 0.71 - 0.76). Conclusions: 68Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to 131I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents.


Sujet(s)
Isotopes du gallium/métabolisme , Radio-isotopes du gallium/métabolisme , Radio-isotopes de l'iode/métabolisme , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Tomographie par émission monophotonique couplée à la tomodensitométrie/méthodes , Tumeurs de la thyroïde/imagerie diagnostique , Tumeurs de la thyroïde/métabolisme , Sujet âgé , Différenciation cellulaire/physiologie , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Projets pilotes , Tomographie par émission de positons couplée à la tomodensitométrie/normes , Études rétrospectives , Tomographie par émission monophotonique couplée à la tomodensitométrie/normes
20.
Clin Transl Oncol ; 23(1): 172-178, 2021 Jan.
Article de Anglais | MEDLINE | ID: mdl-32447644

RÉSUMÉ

PURPOSE: To compare the diagnostic performance of 68Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa). METHODS: From September till December 2018, we prospectively enrolled 25 candidates to 68Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results. RESULTS: Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa. CONCLUSION: In this highly-selected patient population, in comparison to PRI-MUS, 68Ga-PSMA PET/CT shows a higher diagnostic performance.


Sujet(s)
Isotopes du gallium , Radio-isotopes du gallium , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Tumeurs de la prostate/imagerie diagnostique , Radiopharmaceutiques , Échographie/méthodes , Sujet âgé , Sujet âgé de 80 ans ou plus , Humains , Biopsie guidée par l'image/méthodes , Mâle , Adulte d'âge moyen , Études prospectives , Antigène spécifique de la prostate/sang , Tumeurs de la prostate/sang , Tumeurs de la prostate/anatomopathologie
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