73 results on '"Morgat C"'
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2. Opportunities and challenges for targeted radionuclide therapy of prostate cancer using 161Tb
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Morgat, C., Van de Voorde, M., Bodin, S., Champion, C., and Hindié, E.
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- 2023
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3. Les radiotraceurs autres que le PSMA-ligand pour l’imagerie TEP du cancer de prostate
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Withofs, N., Hustinx, R., and Morgat, C.
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- 2023
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4. Mort subite en l’absence de cardiopathie : explorations et prise en charge
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Extramiana, F., Denjoy, I., Morgat, C., Messali, A., Zouaghi, A., Algalarrondo, V., and Leenhardt, A.
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- 2022
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5. Étude dosimétrique de préparations de médicaments radiopharmaceutiques au 68Ga
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Morgat, C., Vimont, D., Hindié, E., Fernandez, P., and Buj, S.
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- 2019
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6. Radiopharmaceuticals targeting PSMA for imaging and/or therapy
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Morgat, C.
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- 2019
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7. ECG descriptors of ventricular repolarization are associated with cardiac events in a gene-specific manner in long QT syndrome patients
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Morgat, C, primary, Denjoy, I, additional, Fressart, V, additional, Badilini, F, additional, Vaglio, M, additional, Messali, A, additional, Maison-Blanche, P, additional, Leenhardt, A, additional, and Extramiana, F, additional
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- 2022
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8. Evaluation of radiopharmaceuticals sorption to 2 and 3-pieces syringes
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DUPIRE, C., CHENNELL, P., Pereira, B., SAUTOU, V., Crauste-Manciet, S., MORGAT, C., Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, and Bonnefoy, Stéphanie
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2021
9. Novel radiolabelled neurotensin analogues containing silylated amino acid for improved neurotensin receptor-1 (NTS1) targeting
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Chastel, A, Fanelli, R, Previti, S, Vimont, D, Zanotti-Fregonara, P, Guillet, B, Garrigue, P, Balasse, L, FERNANDEZ, P, Remond, E, Hindie, E, Cavelier, F, Morgat, C, CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Houston Methodist Research Institute, Partenaires INRAE, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), European-Association-of-Nuclear-Medicine (EANM), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
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Radiomarquage ,neurotensine ,Acide aminé ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience
- Published
- 2019
10. État actuel de l’utilisation en essais cliniques de molécules radiomarquées au 68Ga en France. Exemple du site de Bordeaux
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Morgat, C., Vimont, D., de Clermont Gallerande, H., Mazère, J., Xuereb, F., Bordenave, L., Hindié, E., and Fernandez, P.
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- 2018
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11. Efficacy and tolerance evaluation of an ambulatory use of sacubitril/valsartan among patients with heart failure due to reduced ejection fraction
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Chong-Nguyen, C., primary, Jullien, M., additional, Lescroart, M., additional, Morgat, C., additional, Rolland, T., additional, Temmar, Y., additional, and Ghanem, N., additional
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- 2019
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12. Ciblage du PSMA et du GRPR dans le diagnostic initial de cancer de prostate : étude comparative en micro-imagerie tissulaire avec l’111In-PSMA-617 et l’111In-RM2
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Schollhammer, R., primary, De Clermont, H., additional, Robert, G., additional, Yacoub, M., additional, Quintyn Ranti, M.L., additional, Barthe, N., additional, Vimont, D., additional, Hindie, H., additional, Fernandez, P., additional, and Morgat, C., additional
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- 2019
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13. État actuel de l’utilisation en essais cliniques de molécules radiomarquées au 68Ga en France. Exemple du site de Bordeaux
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Morgat, C., Vimont, D., de Clermont Gallerande, H., Mazère, J., Xuereb, F., Bordenave, L., Hindié, E., and Fernandez, P.
- Abstract
La production de médicaments radiopharmaceutiques (MRP) marqués au 68Ga pour l’imagerie moléculaire par Tomographie d’Emission de Positons couplée à la Tomodensitométrie (TEP/TDM) connaît un essor important. Ces développements sont aujourd’hui accélérés en France avec la disponibilité d’un agoniste des récepteurs de la somatostatine (DOTATOC, Somakit®) disposant d’une autorisation de mise sur le marché (AMM) et de deux inhibiteurs du Prostate Specific Membrane Antigen(PSMA-11 et PSMA-617) sous le régime d’une autorisation temporaire d’utilisation (ATU) nominative. L’intérêt indiscutable de ces MRP et leurs places dans les stratégies diagnostiques actuelles sont le reflet des essais cliniques menés avec notamment le 68Ga-DOTATOC et le 68Ga-PSMA-11. Aujourd’hui, de nouvelles indications et d’autres MRP galliés émergent pour développer davantage l’imagerie moléculaire TEP/TDM. Dans cet article, nous souhaitons relater l’expérience de notre centre Bordelais dans l’élaboration de tels essais cliniques.
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- 2024
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14. A new class of radiopeptides for PET imaging of neuromedin-B receptor: 68Ga-ranatensin analogs
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Morgat, C., primary, Varshney, R., additional, Vimont, D., additional, Savona-Baron, C., additional, Riès, C., additional, Chanseau, C., additional, Bertrand, S. S., additional, Mishra, A. K., additional, Hindié, E., additional, Fernandez, P., additional, and Schulz, J., additional
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- 2016
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15. Correction: A new class of radiopeptides for PET imaging of neuromedin-B receptor: 68Ga-ranatensin analogs
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Morgat, C., primary, Varshney, R., additional, Vimont, D., additional, Savona-Baron, C., additional, Riès, C., additional, Chanseau, C., additional, Bertrand, S. S., additional, Mishra, A. K., additional, Hindié, E., additional, Fernandez, P., additional, and Schulz, J., additional
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- 2016
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16. Étude comparative de la TEP au 68Ga DOTATOC et de la tomoscintigraphie à l’111In-DTPA-octréotide pour le dépistage des tumeurs neuroendocrines duodénopancréatiques des patients porteurs d’une NEM1 : étude pilote
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Vélayoudom-Céphise, F.L., primary, Morgat, C., additional, Schwartz, P., additional, Nunes, M.L., additional, Guyot, M., additional, Schulz, J., additional, Mazère, J., additional, Gaye, D., additional, Hindie, E., additional, Fernandez, P., additional, and Tabarin, A., additional
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- 2015
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17. A new class of radiopeptides for PET imaging of neuromedin-B receptor: 68Ga-ranatensin analogs.
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Morgat, C., Varshney, R., Vimont, D., Savona-Baron, C., Riès, C., Chanseau, C., Bertrand, S. S., Mishra, A. K., Hindié, E., Fernandez, P., and Schulz, J.
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- 2016
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18. Impact of resident training on cardiac electrophysiological procedures.
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Morgat C, Cellier J, Dinanian S, Juin C, Slama MS, Kalyana Sundar S, Extramiana F, and Algalarrondo V
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- Humans, Retrospective Studies, Female, Male, Time Factors, Middle Aged, Aged, Risk Factors, Treatment Outcome, Length of Stay, Cardiac Pacing, Artificial, Catheter Ablation adverse effects, Fluoroscopy, Electric Countershock instrumentation, Defibrillators, Implantable, Curriculum, Learning Curve, Internship and Residency, Operative Time, Arrhythmias, Cardiac physiopathology, Arrhythmias, Cardiac therapy, Arrhythmias, Cardiac diagnosis, Clinical Competence, Electrophysiologic Techniques, Cardiac, Education, Medical, Graduate, Pacemaker, Artificial
- Abstract
Background: Modern management of cardiac arrhythmias often requires interventions in which young physicians must acquire a high level of expertise. However, concerns have been raised about the increase in side effects during procedures performed with resident involvement., Aim: This study aims to identify the effects of resident training on cardiac electrophysiological procedures within a university centre., Methods: In a single-centre study, cardiac arrhythmia procedures were reviewed retrospectively, and resident involvement was scrutinized. Univariate and multivariable models were built for the following outcomes: fluoroscopy time; operative time; length of hospitalization after procedure; and adverse events., Results: We reviewed 991 procedures, 574 without and 417 with resident involvement (650 cardiac pacemakers or defibrillators, 120 generator replacements, 188 electrophysiological studies and 153 radiofrequency ablations). Resident involvement was associated with an increase in fluoroscopy time: +1.7±0.4minutes (P<0.01) for pacemaker implantation; and +2.5±0.9minutes (P=0.01) for electrophysiological studies. Operative time was longer for electrophysiological studies (+10.8±4.9minutes; P=0.03) and pacing implantation (+8.4±2.2minutes; P<0.01). There was no significant association between resident training and adverse events (7.67 vs. 9.83%; P=0.28)., Conclusions: Cardiac electrophysiological procedures performed with resident involvement have a good safety profile. However, resident training modestly, but significantly, prolongs fluoroscopy time and operative time., (Copyright © 2024. Published by Elsevier Masson SAS.)
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- 2024
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19. Rational design of NT-PSMA heterobivalent probes for prostate cancer theranostics.
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Previti S, Bodin S, Rémond E, Vimont D, Hindié E, Morgat C, and Cavelier F
- Abstract
Targeting the prostate-specific membrane antigen (PSMA) with radiopharmaceuticals for imaging and/or therapy has demonstrated significant advancement in the management of prostate cancer patients. However, PSMA targeting remains unsuccessful in prostate cancers with low expression of PSMA, which account for 15% of cases. The neurotensin receptor-1 (NTS
1 ) has been highlighted as a suitable oncotarget for imaging and therapy of PSMA-negative prostate cancer lesions. Therefore, heterobivalent probes targeting both PSMA and NTS1 could improve the prostate cancer management. Herein, we report the development of a branched hybrid probe ( JMV 7489 ) designed to target PSMA and/or NTS1 bearing relevant pharmacophores and DOTA as the chelating agent. The new ligand was synthesized with a hybrid approach, which includes both syntheses in batch and in the solid phase. Saturation binding experiments were next performed on HT-29 and PC3-PIP cells to derive Kd and Bmax values. On the PC3-PIP cells, [68 Ga]Ga- JMV 7489 displayed good affinity towards PSMA ( Kd = 53 ± 17 nM; Bmax = 1393 ± 29 fmol/106 cells) in the same range as the corresponding reference monomer. A lower affinity value towards NTS1 was depicted ( Kd = 157 ± 71 nM; Bmax = 241 ± 42 fmol/106 cells on PC3-PIP cells; Kd = 246 ± 1 nM; Bmax = 151 ± 44 fmol/106 cells on HT-29 cells) and, surprisingly, it was also the case for the corresponding monomer [68 Ga]Ga- JMV 7089 . These results indicate that the DOTA macrocycle and the linker are critical elements to design heterobivalent probes targeting PSMA and NTS1 with high affinity towards NTS1 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2024
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20. How to improve medical students' ECG interpretation skills ? Multicenter survey and results of a comparative study evaluating a new educational approach.
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Chaumont C, Morgat C, Ollitrault P, Brejoux C, Extramiana F, Milliez P, Savoure A, Al Hamoud R, Eltchaninoff H, and Anselme F
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- Humans, Education, Medical, Undergraduate methods, Cardiology education, Female, Male, Surveys and Questionnaires, Educational Measurement, Internship and Residency, Electrocardiography, Clinical Competence standards, Students, Medical
- Abstract
Background: Learning to interpret electrocardiograms (ECGs) is a crucial objective in medical education. Despite its importance, errors in ECGs interpretation are common, and the optimal teaching methods have not yet been clearly established., Objectives: To evaluate students' confidence in ECGs analysis and their opinion on current teaching methods, and to assess the effectiveness of a new ECG educational approach., Methods: First, we conducted a survey on ECG learning among fourth to sixth-year medical students. Second, a 5-week multicenter comparative study was conducted with fourth-year medical students during their cardiology internship. Two different teaching methods were used, assigned by center. The first group participated in 5-minutes workshops 4 times a week using a "reversed classroom" method, supervised by a cardiologist, where students took turns selecting, presenting and discussing ECGs. The control group attended a single 2-hour face-to-face ECG course. All participants completed a 30-minute ECGs analysis test at baseline and after 5 weeks., Results: Out of 401 survey respondents, the confidence levels in ECG interpretation were 3/5 (IQR 2-3) for routine situations and 2/5 (IQR 1-3) for emergency situations. Satisfaction with ECG teaching was low (2/5, IQR 1-3) and 96.3% of respondents favored more extensive ECG training. In the comparative study, 52 students from 3 medical schools were enrolled (control group: n = 27; workshop group: n = 25). Both groups showed significant improvement in exam scores from baseline to 5-week (33/100 ± 12/100 to 44/100 ± 12/100, p < 0.0001 for the control group and 36/100 ± 13/100 to 62/100 ± 12/100, p < 0.0001 for the workshop group). The improvement was significantly greater in the workshop group compared to the control group (+ 26 ± 11 vs. + 11 ± 6, p < 0.001)., Conclusions: Among French medical students who initially reported low confidence and insufficient skills in ECG interpretation, the workshop approach using a "reversed classroom" method was found to be more effective than conventional lecture-based teaching during cardiology internship., (© 2024. The Author(s).)
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- 2024
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21. Palladium-103 ( 103 Pd/ 103m Rh), a promising Auger-electron emitter for targeted radionuclide therapy of disseminated tumor cells - absorbed doses in single cells and clusters, with comparison to 177 Lu and 161 Tb.
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Hindié E, Larouze A, Alcocer-Ávila M, Morgat C, and Champion C
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- Humans, Lutetium therapeutic use, Monte Carlo Method, Neoplasms radiotherapy, Palladium chemistry, Palladium therapeutic use, Palladium administration & dosage, Radioisotopes therapeutic use, Radioisotopes pharmacokinetics
- Abstract
Early use of targeted radionuclide therapy (TRT) to eradicate disseminated tumor cells (DTCs) might offer cure. Selection of appropriate radionuclides is required. This work highlights the potential of
103 Pd (T1/2 = 16.991 d) which decays to103m Rh (T1/2 = 56.12 min) then to stable103 Rh with emission of Auger and conversion electrons. Methods: The Monte Carlo track structure code CELLDOSE was used to assess absorbed doses in single cells (14-μm diameter; 10-μm nucleus) and clusters of 19 cells. The radionuclide was distributed on the cell surface, within the cytoplasm, or in the nucleus. Absorbed doses from103 Pd,177 Lu and161 Tb were compared after energy normalization. The impact of non-uniform cell targeting, and the potential benefit from dual-targeting was investigated. Additional results related to103m Rh, if used directly, are provided. Results: In the single cell, and depending on radionuclide distribution,103 Pd delivered 7- to 10-fold higher nuclear absorbed dose and 9- to 25-fold higher membrane dose than177 Lu. In the 19-cell clusters,103 Pd absorbed doses also largely exceeded177 Lu. In both situations,161 Tb stood in-between103 Pd and177 Lu. Non-uniform targeting, considering four unlabeled cells within the cluster, resulted in moderate-to-severe dose heterogeneity. For example, with intranuclear103 Pd, unlabeled cells received only 14% of the expected nuclear dose. Targeting with two103 Pd-labeled radiopharmaceuticals minimized dose heterogeneity. Conclusion:103 Pd, a next-generation Auger emitter, can deliver substantially higher absorbed doses than177 Lu to single tumor cells and cell clusters. This may open new horizons for the use of TRT in adjuvant or neoadjuvant settings, or for targeting minimal residual disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)- Published
- 2024
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22. Re: Renu S. Eapen, James P. Buteau, Price Jackson, et al. Administering [ 177 Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study. Eur Urol. 2024;85:217-226.
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Hindié E, Champion C, and Morgat C
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- Humans, Male, Heterocyclic Compounds, 1-Ring therapeutic use, Dipeptides therapeutic use, Lutetium, Clinical Trials, Phase I as Topic, Prostate-Specific Antigen, Prostatectomy methods, Prostatic Neoplasms surgery
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- 2024
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23. Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients.
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Morgat C, Fressart V, Porretta AP, Neyroud N, Messali A, Temmar Y, Algalarrondo V, Surget E, Bloch A, Leenhardt A, Denjoy I, and Extramiana F
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- Humans, Female, Male, Risk Assessment, Risk Factors, Child, Electrocardiography, Child, Preschool, Heterozygote, Mutation, Jervell-Lange Nielsen Syndrome genetics, Jervell-Lange Nielsen Syndrome physiopathology, Genetic Predisposition to Disease, Infant, Adult, Adolescent, Phenotype, Retrospective Studies, Death, Sudden, Cardiac etiology, Young Adult, Incidence, KCNQ1 Potassium Channel genetics, Romano-Ward Syndrome genetics, Romano-Ward Syndrome physiopathology, Romano-Ward Syndrome diagnosis
- Abstract
Aims: KCNQ1 mutations cause QTc prolongation increasing life-threatening arrhythmias risks. Heterozygous mutations [type 1 long QT syndrome (LQT1)] are common. Homozygous KCNQ1 mutations cause type 1 Jervell and Lange-Nielsen syndrome (JLNS) with deafness and higher sudden cardiac death risk. KCNQ1 variants causing JLNS or LQT1 might have distinct phenotypic expressions in heterozygous patients. The aim of this study is to evaluate QTc duration and incidence of long QT syndrome-related cardiac events according to genetic presentation., Methods and Results: We enrolled LQT1 or JLNS patients with class IV/V KCNQ1 variants from our inherited arrhythmia clinic (September 1993 to January 2023). Medical history, ECG, and follow-up were collected. Additionally, we conducted a thorough literature review for JLNS variants. Survival curves were compared between groups, and multivariate Cox regression models identified genetic and clinical risk factors. Among the 789 KCNQ1 variant carriers, 3 groups were identified: 30 JLNS, 161 heterozygous carriers of JLNS variants (HTZ-JLNS), and 550 LQT1 heterozygous carriers of non-JLNS variants (HTZ-Non-JLNS). At diagnosis, mean age was 3.4 ± 4.7 years for JLNS, 26.7 ± 21 years for HTZ-JLNS, and 26 ± 21 years for HTZ-non-JLNS; 55.3% were female; and the mean QTc was 551 ± 54 ms for JLNS, 441 ± 32 ms for HTZ-JLNS, and 467 ± 36 ms for HTZ-Non-JLNS. Patients with heterozygous JLNS mutations (HTZ-JLNS) represented 22% of heterozygous KCNQ1 variant carriers and had a lower risk of cardiac events than heterozygous non-JLNS variant carriers (HTZ-Non-JLNS) [hazard ratio (HR) = 0.34 (0.22-0.54); P < 0.01]. After multivariate analysis, four genetic parameters were independently associated with events: haploinsufficiency [HR = 0.60 (0.37-0.97); P = 0.04], pore localization [HR = 1.61 (1.14-1.2.26); P < 0.01], C-terminal localization [HR = 0.67 (0.46-0.98); P = 0.04], and group [HR = 0.43 (0.27-0.69); P < 0.01]., Conclusion: Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events than other LQT1 patients., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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24. Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific?
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Hermida A, Gourraud JB, Denjoy I, Fressart V, Kyndt F, Maltret A, Khraiche D, Klug D, Mabo P, Sacher F, Maury P, Winum P, Defaye P, Clerici G, Babuty D, Elbez Y, Morgat C, Surget E, Messali A, De Jode P, Clédel A, Minois D, Maison-Blanche P, Bloch A, Leenhardt A, Probst V, and Extramiana F
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- Humans, Male, Young Adult, Adult, Female, Electrocardiography, Syncope, Adrenergic beta-Antagonists therapeutic use, Long QT Syndrome drug therapy, Long QT Syndrome genetics, Long QT Syndrome diagnosis, Heart Arrest complications
- Abstract
Background: The efficacy of beta-blocker treatment in type 3 long QT syndrome (LQT3) remains debated., Objectives: The purpose of this study was to test the hypothesis that beta-blocker use is associated with cardiac events (CEs) in a French cohort of LQT3 patients., Methods: All patients with a likely pathogenic/pathogenic variant in the SCN5A gene (linked to LQT3) were included and followed-up. Documented ventricular tachycardia/ventricular fibrillation, torsades de pointes, aborted cardiac arrest, sudden death, and appropriate shocks were considered as severe cardiac events (SCEs). CEs also included syncope., Results: We included 147 patients from 54 families carrying 23 variants. Six of the patients developed symptoms before the age of 1 year and were analyzed separately. The 141 remaining patients (52.5% male; median age at diagnosis 24.0 years) were followed-up for a median of 11 years. The probabilities of a CE and an SCE from birth to the age of 40 were 20.5% and 9.9%, respectively. QTc prolongation (hazard ratio [HR] 1.12 [1.0-1.2]; P = .005]) and proband status (HR 4.07 [1.9-8.9]; P <.001) were independently associated with the occurrence of CEs. Proband status (HR 8.13 [1.7-38.8]; P = .009) was found to be independently associated with SCEs, whereas QTc prolongation (HR 1.11 [1.0-1.3]; P = .108) did not reach statistical significance. The cumulative probability of the age at first CE/SCE was not lower in patients treated with a beta-blocker., Conclusion: In agreement with the literature, proband status and lengthened QTc were associated with a higher risk of CEs. Our data do not show a protective effect of beta-blocker treatment., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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25. Development of Radiopharmaceuticals for NPY Receptor-5 (Y5) Nuclear Imaging in Tumors by Synthesis of Specific Agonists and Investigation of Their Binding Mode.
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Bodin S, Peuker LC, Jestin E, Alves ID, Velasco V, Ait-Arsa I, Schollhammer R, Lamare F, Vimont D, MacGrogan G, Hindié E, Beck-Sickinger AG, and Morgat C
- Subjects
- Male, Mice, Humans, Animals, Radiopharmaceuticals, Gallium Radioisotopes, Mice, Nude, Tissue Distribution, Chelating Agents, Positron-Emission Tomography methods, Receptors, Neuropeptide Y metabolism, Prostatic Neoplasms
- Abstract
The neuropeptide-Y (NPY) family acts through four G protein-coupled receptor subtypes in humans, namely, Y
1 , Y2 , Y4 , and Y5 . A growing body of evidence suggest the involvement of the NPY system in several cancers, notably the Y5 subtype, thus acting as a relevant target for the development of radiopharmaceuticals for imaging or targeted radionuclide therapy (TRT). Here, the [cPP(1-7),NPY(19-23),Ala31 ,Aib32 ,Gln34 ]hPP scaffold, further referred to as sY5 ago, was modified with a DOTA chelator and radiolabeled with68 Ga and111 In and investigated in vitro and in vivo using the MCF-7 model. For in vivo studies, MCF-7 cells were orthotopically implanted in female nude mice and imaging with small animal positron emission tomography/computed tomography (μPET/CT) was performed. At the end of imaging, the mice were sacrificed. A scrambled version of sY5 ago, which was also modified with a DOTA chelator, served as a negative control (DOTA-[Nle]sY5 ago_scrambled). sY5 ago and DOTA-sY5 ago showed subnanomolar affinity toward the Y5 (0.9 ± 0.1 and 0.8 ± 0.1 nM, respectively) and a single binding site at the Y5 was identified. [68 Ga]Ga-DOTA-sY5 ago and [111 In]In-DOTA-sY5 ago were hydrophilic and showed high specific internalization (1.61 ± 0.75%/106 cells at 1 h) and moderate efflux (55% of total binding externalized at 45 min). On μPET/CT images, most of the signal was depicted in the kidneys and the liver. MCF-7 tumors were clearly visualized. On biodistribution studies, [68 Ga]Ga-DOTA-sY5 ago was eliminated by the kidneys (∼60 %ID/g). The kidney uptake is Y5 -mediated. A specific uptake was also noted in the liver (5.09 ± 1.15 %ID/g vs 1.13 ± 0.21 %ID/g for [68 Ga]Ga-DOTA-[Nle]sY5 ago_scrambled, p < 0.05), the lungs (1.03 ± 0.34 %ID/g vs 0.20 %ID/g, p < 0.05), and the spleen (0.85 ± 0.09%ID/g vs 0.16 ± 0.16%ID/g, p < 0.05). In MCF-7 tumors, [68 Ga]Ga-DOTA-sY5 ago showed 12-fold higher uptake than [68 Ga]Ga-DOTA-[Nle]sY5 ago_scrambled (3.43 ± 2.32 vs 0.27 ± 0.15 %ID/g, respectively, p = 0.0008) at 1 h post-injection. Finally, a proof-of-principle tissular micro-imaging study on a human primary cancer sample showed weak binding of [111 In]In-DOTA-sY5 ago in prostatic intra-neoplasia and high binding in the ISUP1 lesion while normal prostate was free of signal.- Published
- 2023
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26. Membrane and Nuclear Absorbed Doses from 177 Lu and 161 Tb in Tumor Clusters: Effect of Cellular Heterogeneity and Potential Benefit of Dual Targeting-A Monte Carlo Study.
- Author
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Larouze A, Alcocer-Ávila M, Morgat C, Champion C, and Hindié E
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- Humans, Radiopharmaceuticals therapeutic use, Lutetium therapeutic use, Radioisotopes therapeutic use, Neoplasms drug therapy
- Abstract
Early use of targeted radionuclide therapy to eradicate tumor cell clusters and micrometastases might offer cure. However, there is a need to select appropriate radionuclides and assess the potential impact of heterogeneous targeting. Methods: The Monte Carlo code CELLDOSE was used to assess membrane and nuclear absorbed doses from
177 Lu and161 Tb (β- -emitter with additional conversion and Auger electrons) in a cluster of 19 cells (14-μm diameter, 10-μm nucleus). The radionuclide distributions considered were cell surface, intracytoplasmic, or intranuclear, with 1,436 MeV released per labeled cell. To model heterogeneous targeting, 4 of the 19 cells were unlabeled, their position being stochastically determined. We simulated situations of single targeting, as well as dual targeting, with the 2 radiopharmaceuticals aiming at different targets. Results:161 Tb delivered 2- to 6-fold higher absorbed doses to cell membranes and 2- to 3-fold higher nuclear doses than177 Lu. When all 19 cells were targeted, membrane and nuclear absorbed doses were dependent mainly on radionuclide location. With cell surface location, membrane absorbed doses were substantially higher than nuclear absorbed doses, both with177 Lu (38-41 vs. 4.7-7.2 Gy) and with161 Tb (237-244 vs. 9.8-15.1 Gy). However, when 4 cells were not targeted by the cell surface radiopharmaceutical, the membranes of these cells received on average only 9.6% of the177 Lu absorbed dose and 2.9% of the161 Tb dose, compared with a cluster with uniform cell targeting, whereas the impact on nuclear absorbed doses was moderate. With an intranuclear radionuclide location, the nuclei of unlabeled cells received only 17% of the177 Lu absorbed dose and 10.8% of the161 Tb dose, compared with situations with uniform targeting. With an intracytoplasmic location, nuclear and membrane absorbed doses to unlabeled cells were one half to one quarter those obtained with uniform targeting, both for177 Lu and for161 Tb. Dual targeting was beneficial in minimizing absorbed dose heterogeneities. Conclusion: To eradicate tumor cell clusters,161 Tb may be a better candidate than177 Lu. Heterogeneous cell targeting can lead to substantial heterogeneities in absorbed doses. Dual targeting was helpful in reducing dose heterogeneity and should be explored in preclinical and clinical studies., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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27. Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis.
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Louis B, Nail V, Nachar O, Bouhlel A, Moyon A, Balasse L, Simoncini S, Chabert A, Fernandez S, Brige P, Hache G, Tintaru A, Morgat C, Dignat-George F, Garrigue P, and Guillet B
- Subjects
- Animals, Mice, Swine, Apelin, Apelin Receptors, Gallium Radioisotopes, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography methods, Molecular Imaging methods, Oligopeptides, Adenocarcinoma, Colonic Neoplasms
- Abstract
APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([
68 Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [67 Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [68 Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [68 Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [68 Ga]Ga-AP747 and [68 Ga]Ga-RGD2 small animal PET/CT. [68 Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [68 Ga]Ga-RGD2 . Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [68 Ga]Ga-AP747 PET signal was more than twice higher than that of [68 Ga]Ga-RGD2 on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [68 Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [68 Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [68 Ga]Ga-RGD2 ., (© 2023. The Author(s).)- Published
- 2023
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28. Modular One-Pot Strategy for the Synthesis of Heterobivalent Tracers.
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Bailly T, Bodin S, Goncalves V, Denat F, Morgat C, Prignon A, and Valverde IE
- Abstract
Bivalent ligands, i.e., molecules having two ligands covalently connected by a linker, have been gathering attention since the first description of their pharmacological potential in the early 80s. However, their synthesis, particularly of labeled heterobivalent ligands, can still be cumbersome and time-consuming. We herein report a straightforward procedure for the modular synthesis of labeled heterobivalent ligands (HBLs) using dual reactive 3,6-dichloro-1,2,4,5-tetrazine as a starting material and suitable partners for sequential S
N Ar and inverse electron-demand Diels-Alder (IEDDA) reactions. This assembly method conducted in a stepwise or in a sequential one-pot manner provides quick access to multiple HBLs. A conjugate combining ligands toward the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPR) was radiolabeled, and its biological activity was assessed in vitro and in vivo (receptor binding affinity, biodistribution, imaging) as an illustration that the assembly methodology preserves the tumor targeting properties of the ligands., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)- Published
- 2023
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29. Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.
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Schollhammer R, Quintyn Ranty ML, de Clermont Gallerande H, Cavelier F, Valverde IE, Vimont D, Hindié E, and Morgat C
- Abstract
The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal., Methods: First, we prospectively performed neurotensin receptor-1 (NTS
1 ) IHC in a series of patients receiving both [68 Ga]Ga-PSMA-617 and [68 Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n = 16). Next, we aimed at confirming the PSMA/GRP-R/NTS1 expression profile by retrospective autoradiography (n = 46) using a specific radiopharmaceuticals study and also aimed to decipher the expression of less-investigated targets such as NTS2 , SST2 and CXCR4., Results: In the IHC study, all samples with negative PSMA staining (two patients with ISUP 2 and one with ISUP 3) were strongly positive for NTS1 staining. No samples were negative for all three stains-for PSMA, GRP-R or NTS1 . In the autoradiography study, binding of [111 In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [111 In]In-PSMA-617 (9%). In these cases, binding of [111 n]In-JMV 6659 and [111 In]In-JMV 7488 towards NTS1 and NTS2 was high., Conclusions: Targeting PSMA and NTS1 /NTS2 could allow for the detection of all intraprostatic lesions.- Published
- 2023
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30. Comparison of 68 Ga-PSMA-617 PET/CT and 68 Ga-RM2 PET/CT in Patients with Localized Prostate Cancer Who Are Candidates for Radical Prostatectomy: A Prospective, Single-Arm, Single-Center, Phase II Study.
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Schollhammer R, Robert G, Asselineau J, Yacoub M, Vimont D, Balamoutoff N, Bladou F, Bénard A, Hindié E, Gallerande HC, and Morgat C
- Subjects
- Male, Humans, Positron Emission Tomography Computed Tomography methods, Gallium Radioisotopes, Prospective Studies, Prostatectomy, Prostate pathology, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms surgery, Prostatic Neoplasms pathology
- Abstract
Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with
68 Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and68 Ga-RM2 (68 Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm3 ),68 Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and68 Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered68 Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of68 Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 ( P < 0.0001) or 2 ( P = 0.0002). There were no significant differences in uptake between ISUP scores for68 Ga-RM2. Median68 Ga-RM2 SUVmax was significantly higher than median68 Ga-PSMA-617 SUVmax in the ISUP-2 subgroup ( P = 0.01). Conclusion:68 Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and68 Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
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31. Design, Synthesis, and Biological Evaluation of the First Radio-Metalated Neurotensin Analogue Targeting Neurotensin Receptor 2.
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Bodin S, Previti S, Jestin E, Vimont D, Ait-Arsa I, Lamare F, Rémond E, Hindié E, Cavelier F, and Morgat C
- Abstract
Neurotensin receptor 2 (NTS
2 ) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS2 overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS2 . JMV 7488 (DOTA-(βAla)2 -Lys-Lys-Pro-(D)Trp-Ile-TMSAla-OH) was prepared using solid-phase peptide synthesis, then purified, radiolabeled with68 Ga and111 In, and investigated in vitro on HT-29 cells and MCF-7 cells, respectively, and in vivo on HT-29 xenografts. [68 Ga]Ga-JMV 7488 and [111 In]In-JMV 7488 were quite hydrophilic (logD7.4 = -3.1 ± 0.2 and -2.7 ± 0.2, respectively, p < 0.0001). Saturation binding studies showed good affinity toward NTS2 ( KD = 38 ± 17 nM for [68 Ga]Ga-JMV 7488 on HT-29 and 36 ± 10 nM on MCF-7 cells; KD = 36 ± 4 nM for [111 In]In-JMV 7488 on HT-29 and 46 ± 1 nM on MCF-7 cells) and good selectivity (no NTS1 binding up to 500 nM). On cell-based evaluation, [68 Ga]Ga-JMV 7488 and [111 In]In-JMV 7488 showed high and fast NTS2 -mediated internalization of 24 ± 5 and 25 ± 11% at 1 h for [111 In]In-JMV 7488, respectively, along with low NTS2 -membrane binding (<8%). Efflux was as high as 66 ± 9% at 45 min for [68 Ga]Ga-JMV 7488 on HT-29 and increased for [111 In]In-JMV 7488 up to 73 ± 16% on HT-29 and 78 ± 9% on MCF-7 cells at 2 h. Maximum intracellular calcium mobilization of JMV 7488 was 91 ± 11% to that of levocabastine, a known NTS2 agonist on HT-29 cells demonstrating the agonist behavior of JMV 7488. In nude mice bearing HT-29 xenograft, [68 Ga]Ga-JMV 7488 showed a moderate but promising significant tumor uptake in biodistribution studies that competes well with other nonmetalated radiotracers targeting NTS2 . Significant uptake was also depicted in lungs. Interestingly, mice prostate also demonstrated [68 Ga]Ga-JMV 7488 uptake although the mechanism was not NTS2 -mediated., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)- Published
- 2023
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32. Expression of neurotensin receptor-1 (NTS 1 ) in primary breast tumors, cellular distribution, and association with clinical and biological factors.
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Morgat C, Brouste V, Chastel A, Vélasco V, Macgrogan G, and Hindié E
- Subjects
- Biological Factors, Cell Line, Tumor, Female, Humans, Radiopharmaceuticals, Breast Neoplasms genetics, Receptors, Neurotensin genetics
- Abstract
Purpose: Neurotensin receptor-1 (NTS
1 ) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified., Methods: We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS1 expression and clinical, pathological, and biological parameters, as well as patient outcomes., Results: Out of 1419 primary breast tumors, moderate to strong positivity for NTS1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main "correlates" of a nuclear location of NTS1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS1 -positive samples, cytoplasmic expression of NTS1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS1 nuclear staining. Ancillary analysis showed NTS1 expression in 73% of invaded lymph nodes from NTS1 -positive primaries., Conclusion: NTS1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS1 -targeting strategy, including radiopharmaceuticals for imaging and therapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2021
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33. Targeted radioactive therapy for prostate cancer.
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Hindié E, Morgat C, Alcocer-Ávila ME, and Champion C
- Subjects
- Humans, Male, Prostatic Neoplasms radiotherapy
- Abstract
Competing Interests: We declare no competing interests.
- Published
- 2021
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34. 68 Ga-Radiolabeling and Pharmacological Characterization of a Kit-Based Formulation of the Gastrin-Releasing Peptide Receptor (GRP-R) Antagonist RM2 for Convenient Preparation of [ 68 Ga]Ga-RM2.
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Chastel A, Vimont D, Claverol S, Zerna M, Bodin S, Berndt M, Chaignepain S, Hindié E, and Morgat C
- Abstract
Background: [
68 Ga]Ga-RM2 is a potent Gastrin-Releasing Peptide-receptor (GRP-R) antagonist for imaging prostate cancer and breast cancer, currently under clinical evaluation in several specialized centers around the world. Targeted radionuclide therapy of GRP-R-expressing tumors is also being investigated. We here report the characteristics of a kit-based formulation of RM2 that should ease the development of GRP-R imaging and make it available to more institutions and patients., Methods: Stability of the investigated kits over one year was determined using LC/MS/MS and UV-HPLC. Direct68 Ga-radiolabeling was optimized with respect to buffer (pH), temperature, reaction time and shaking time. Conventionally prepared [68 Ga]Ga-RM2 using an automated synthesizer was used as a comparator. Finally, the [68 Ga]Ga-RM2 product was assessed with regards to hydrophilicity, affinity, internalization, membrane bound fraction, calcium mobilization assay and efflux, which is a valuable addition to the in vivo literature., Results: The kit-based formulation, kept between 2 °C and 8 °C, was stable for over one year. Using acetate buffer pH 3.0 in 2.5-5.1 mL total volume, heating at 100 °C during 10 min and cooling down for 5 min, the [68 Ga]Ga-RM2 produced by kit complies with the requirements of the European Pharmacopoeia. Compared with the module production route, the [68 Ga]Ga-RM2 produced by kit was faster, displayed higher yields, higher volumetric activity and was devoid of ethanol. In in vitro evaluations, the [68 Ga]Ga-RM2 displayed sub-nanomolar affinity (Kd = 0.25 ± 0.19 nM), receptor specific and time dependent membrane-bound fraction of 42.0 ± 5.1% at 60 min and GRP-R mediated internalization of 24.4 ± 4.3% at 30 min. The [nat Ga]Ga-RM2 was ineffective in stimulating intracellular calcium mobilization. Finally, the efflux of the internalized activity was 64.3 ± 6.5% at 5 min., Conclusion: The kit-based formulation of RM2 is suitable to disseminate GRP-R imaging and therapy to distant hospitals without complex radiochemistry equipment.- Published
- 2021
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35. In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease.
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Schollhammer R, Lepreux S, Barthe N, Vimont D, Rullier A, Sibon I, Berard X, Zhang A, Kimura Y, Fujita M, Innis RB, Zanotti-Fregonara P, and Morgat C
- Abstract
Background: Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [
11 C]-PBR28 and [18 F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18 F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18 F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11 C]-PBR28., Results: All in vitro sections showed specific binding of [18 F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11 C]-PBR28 or [18 F]-PBR06 was negative in all participants., Conclusion: Despite good uptake on surgical samples in vitro, [11 C]-PBR28 and [18 F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease., Trial Registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .- Published
- 2021
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36. Silicon-Containing Neurotensin Analogues as Radiopharmaceuticals for NTS 1 -Positive Tumors Imaging.
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Fanelli R, Chastel A, Previti S, Hindié E, Vimont D, Zanotti-Fregonara P, Fernandez P, Garrigue P, Lamare F, Schollhammer R, Balasse L, Guillet B, Rémond E, Morgat C, and Cavelier F
- Subjects
- Animals, HT29 Cells, Humans, Mice, Nude, Neoplasms diagnostic imaging, Neurotensin analogs & derivatives, Positron-Emission Tomography methods, Radiopharmaceuticals chemistry, Receptors, Neurotensin analysis, Silicon chemistry
- Abstract
Several independent studies have demonstrated the overexpression of NTS
1 in various malignancies, which make this receptor of interest for imaging and therapy. To date, radiolabeled neurotensin analogues suffer from low plasmatic stability and thus insufficient availability for high uptake in tumors. We report the development of68 Ga-radiolabeled neurotensin analogues with improved radiopharmaceutical properties through the introduction of the silicon-containing amino acid trimethylsilylalanine (TMSAla). Among the series of novel radiolabeled neurotensin analogues, [68 Ga] Ga- JMV6659 exhibits high hydrophilicity (log D7.4 = -3.41 ± 0.14), affinity in the low nanomolar range toward NTS1 ( Kd = 6.29 ± 1.37 nM), good selectivity ( Kd NTS1 / Kd NTS2 = 35.9), and high NTS1 -mediated internalization. It has lower efflux and prolonged plasmatic half-life in human plasma as compared to the reference compound ([68 Ga]Ga-JMV6661 bearing the minimum active fragment of neurotensin and the same linker and chelate as other analogues). In nude mice bearing HT-29 xenograft, [68 Ga]Ga-JMV6659 uptake reached 7.8 ± 0.54 %ID/g 2 h post injection. Uptake was decreased to 1.38 ± 0.71 %ID/g with injection of excess of non-radioactive neurotensin. Radiation dose as extrapolated to human was estimated as 2.35 ± 0.6 mSv for a standard injected activity of 100MBq. [68 Ga]Ga-JMV6659 was identified as a promising lead compound suitable for PET imaging of NTS1 -expressing tumors.- Published
- 2020
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37. Radiation doses from 161 Tb and 177 Lu in single tumour cells and micrometastases.
- Author
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Alcocer-Ávila ME, Ferreira A, Quinto MA, Morgat C, Hindié E, and Champion C
- Abstract
Background: Targeted radionuclide therapy (TRT) is gaining importance. For TRT to be also used as adjuvant therapy or for treating minimal residual disease, there is a need to increase the radiation dose to small tumours. The aim of this in silico study was to compare the performances of
161 Tb (a medium-energy β- emitter with additional Auger and conversion electron emissions) and177 Lu for irradiating single tumour cells and micrometastases, with various distributions of the radionuclide., Methods: We used the Monte Carlo track-structure (MCTS) code CELLDOSE to compute the radiation doses delivered by161 Tb and177 Lu to single cells (14 μm cell diameter with 10 μm nucleus diameter) and to a tumour cluster consisting of a central cell surrounded by two layers of cells (18 neighbours). We focused the analysis on the absorbed dose to the nucleus of the single tumoral cell and to the nuclei of the cells in the cluster. For both radionuclides, the simulations were run assuming that 1 MeV was released per μm3 (1436 MeV/cell). We considered various distributions of the radionuclides: either at the cell surface, intracytoplasmic or intranuclear., Results: For the single cell, the dose to the nucleus was substantially higher with161 Tb compared to177 Lu, regardless of the radionuclide distribution: 5.0 Gy vs. 1.9 Gy in the case of cell surface distribution; 8.3 Gy vs. 3.0 Gy for intracytoplasmic distribution; and 38.6 Gy vs. 10.7 Gy for intranuclear location. With the addition of the neighbouring cells, the radiation doses increased, but remained consistently higher for161 Tb compared to177 Lu. For example, the dose to the nucleus of the central cell of the cluster was 15.1 Gy for161 Tb and 7.2 Gy for177 Lu in the case of cell surface distribution of the radionuclide, 17.9 Gy for161 Tb and 8.3 Gy for177 Lu for intracytoplasmic distribution and 47.8 Gy for161 Tb and 15.7 Gy for177 Lu in the case of intranuclear location., Conclusion:161 Tb should be a better candidate than177 Lu for irradiating single tumour cells and micrometastases, regardless of the radionuclide distribution.- Published
- 2020
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38. Design, synthesis, and biological evaluation of a multifunctional neuropeptide-Y conjugate for selective nuclear delivery of radiolanthanides.
- Author
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Chastel A, Worm DJ, Alves ID, Vimont D, Petrel M, Fernandez S, Garrigue P, Fernandez P, Hindié E, Beck-Sickinger AG, and Morgat C
- Abstract
Background: Targeting G protein-coupled receptors on the surface of cancer cells with peptide ligands is a promising concept for the selective tumor delivery of therapeutically active cargos, including radiometals for targeted radionuclide therapy (TRT). Recently, the radiolanthanide terbium-161 (
161 Tb) gained significant interest for TRT application, since it decays with medium-energy β-radiation but also emits a significant amount of conversion and Auger electrons with short tissue penetration range. The therapeutic efficiency of radiometals emitting Auger electrons, like161 Tb, can therefore be highly boosted by an additional subcellular delivery into the nucleus, in order to facilitate maximum dose deposition to the DNA. In this study, we describe the design of a multifunctional, radiolabeled neuropeptide-Y (NPY) conjugate, to address radiolanthanides to the nucleus of cells naturally overexpressing the human Y1 receptor (hY1 R). By using solid-phase peptide synthesis, the hY1 R-preferring [F7 ,P34 ]-NPY was modified with a fatty acid, a cathepsin B-cleavable linker, followed by a nuclear localization sequence (NLS), and a DOTA chelator (compound pb12). In this proof-of-concept study, labeling was performed with either native terbium-159 (nat Tb), as surrogate for161 Tb, or with indium-111 (111 In)., Results: [nat Tb]Tb-pb12 showed a preserved high binding affinity to endogenous hY1 R on MCF-7 cells and was able to induce receptor activation and internalization similar to the hY1 R-preferring [F7 ,P34 ]-NPY. Specific internalization of the111 In-labeled conjugate into MCF-7 cells was observed, and importantly, time-dependent nuclear uptake of111 In was demonstrated. Study of metabolic stability showed that the peptide is insufficiently stable in human plasma. This was confirmed by injection of [111 In]In-pb12 in nude mice bearing MCF-7 xenograft which showed specific uptake only at very early time point., Conclusion: The multifunctional NPY conjugate with a releasable DOTA-NLS unit represents a promising concept for enhanced TRT with Auger electron-emitting radiolanthanides. Our research is now focusing on improving the reported concept with respect to the poor plasmatic stability of this promising radiopeptide.- Published
- 2020
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39. 68Ga-PSMA-617 Compared With 68Ga-RM2 and 18F-FCholine PET/CT for the Initial Staging of High-Risk Prostate Cancer.
- Author
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Schollhammer R, de Clermont Gallerande H, Robert G, Yacoub M, Vimont D, Hindié E, Fernandez P, and Morgat C
- Subjects
- Aged, Humans, Male, Neoplasm Staging, Prostate-Specific Antigen, Prostatectomy, Prostatic Neoplasms surgery, Risk, Choline analogs & derivatives, Dipeptides, Gallium Radioisotopes, Heterocyclic Compounds, 1-Ring, Oligopeptides, Positron Emission Tomography Computed Tomography methods, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology
- Abstract
Ga-labeled prostate-specific membrane antigen inhibitors and Ga-labeled gastrin-releasing peptide receptor antagonists showed interesting results for staging biochemically recurrent prostate cancer. In this case, Ga-prostate-specific membrane antigen-617 PET/CT, Ga-RM2 PET/CT, and F-choline PET/CT were performed in a patient (66-year-old man, prostate-specific antigen = 6.7 ng/mL) with biopsy-proven Gleason 9 (5 + 4) prostate cancer, candidate for radical prostatectomy and lymph node dissection.
- Published
- 2019
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40. Comparison of the radiolabeled PSMA-inhibitor 111 In-PSMA-617 and the radiolabeled GRP-R antagonist 111 In-RM2 in primary prostate cancer samples.
- Author
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Schollhammer R, De Clermont Gallerande H, Yacoub M, Quintyn Ranty ML, Barthe N, Vimont D, Hindié E, Fernandez P, and Morgat C
- Abstract
Purpose: Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRP-R) are expressed in prostate cancer and can be targeted with radiolabeled inhibitors and antagonists. Their performances for the initial characterization of prostatic tumors have been barely evaluated but never compared. We aimed to gather comparative preclinical data of the role of PSMA and GRP-R targeting in prostate cancer., Procedures: We retrospectively studied 20 frozen prostatectomy samples with various metastatic risks of the D'Amico classification. Tissue samples were investigated by tissular microimaging using the radiolabeled PSMA inhibitor
111 In-PSMA-617 and the radiolabeled GRP-R antagonist111 In-RM2. Bindings of the two radiopharmaceuticals were compared to histology and clinico-biological data (Gleason score, PSA values, metastatic risks)., Results: Binding of111 In-PSMA-617 was high whatever the metastatic risk (p = 0.665), Gleason score (p = 0.555), or PSA value (p = 0.404) while111 In-RM2 exhibited a significantly higher binding in the low metastatic risk group (p = 0.046), in the low PSA value group (p = 0.001), and in samples with Gleason 6 score (p = 0.006)., Conclusion: PSMA and GRP-R based imaging might have complementary performances for the initial characterization of prostatic tumors. Prospective clinical studies comparing the two tracers in this setting are needed.- Published
- 2019
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41. Early use of abiraterone and radium-223 in metastatic prostate cancer.
- Author
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Hindié E and Morgat C
- Subjects
- Abiraterone Acetate, Androstenes, Double-Blind Method, Humans, Male, Prednisolone, Prednisone, Prostatic Neoplasms, Castration-Resistant, Radium
- Published
- 2019
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42. Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases.
- Author
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Morgat C, Chastel A, Molinie V, Schollhammer R, Macgrogan G, Vélasco V, Malavaud B, Fernandez P, and Hindié E
- Subjects
- Blotting, Western, HT29 Cells, Humans, In Vitro Techniques, Lymphatic Metastasis pathology, Male, Microscopy, Confocal, Neuropeptides metabolism, PC-3 Cells, Prostate pathology, Prostatic Hyperplasia metabolism, Prostatic Hyperplasia pathology, Prostatic Neoplasms pathology, Xenograft Model Antitumor Assays, Prostate metabolism, Prostatic Neoplasms metabolism, Receptors, Neurotensin metabolism
- Abstract
Neurotensin and its high-affinity receptor, NTR₁, are involved in the growth of various tumors. Few data are available regarding NTR₁ expression in normal and tumoral human prostate tissue samples. NTR₁ expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available). NTR₁-staining was negative in normal prostate and BPH samples. NTR₁ was overexpressed in four out of 44 (9.1%) primary tumors. There was no clear association between NTR₁ overexpression and age, PSA-values, Gleason score, pT-status, nodal-status, or margin. NTR₁ was expressed at a high level of five out of 15 (33.3%) metastatic lymph nodes. NTR₁ overexpression was thus more frequent in metastatic lymph nodes than in primary tumors ( p = 0.038). In this limited series of samples, NTR₁ overexpression was observed in few primary prostate cancers. Upregulation was more frequent in related lymph nodes. The presence of this target in metastatic lymph nodes may open new perspectives for imaging and radionuclide therapy of prostate cancer. Factors driving NTR₁ expression in primary prostate cancer and in nodal and distant metastases still need to be characterized.
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- 2019
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43. Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples.
- Author
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Morgat C, Schollhammer R, Macgrogan G, Barthe N, Vélasco V, Vimont D, Cazeau AL, Fernandez P, and Hindié E
- Subjects
- Female, Gallium Radioisotopes pharmacokinetics, Humans, Immunohistochemistry, Lymphatic Metastasis diagnostic imaging, Positron Emission Tomography Computed Tomography, Radiopharmaceuticals pharmacokinetics, Receptor, ErbB-2 metabolism, Receptors, Bombesin antagonists & inhibitors, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Retrospective Studies, Breast Neoplasms diagnostic imaging, Breast Neoplasms metabolism, Fluorodeoxyglucose F18 pharmacokinetics, Oligopeptides pharmacokinetics, Receptors, Bombesin metabolism
- Abstract
The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. 68Ga-RM2 binding and 18F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 breast cancer samples (10 primaries and 4 associated metastatic lymph nodes). Results were then assessed against ER expression, progesterone receptor (PR) expression, HER2 over-expression or not and Ki-67 expression. GRPR immunohistochemistry (IHC) was also performed on all samples. We also retrospectively compared 68Ga-RM2 and 18F-FDG bindings to 18F-FDG SUVmax on the pre-therapeutic PET/CT examination, if available. 68Ga-RM2 binding was significantly higher in tumors expressing GRPR on IHC than in GRPR-negative tumors (P = 0.022). In ER+ tumors, binding of 68Ga-RM2 was significantly higher than 18F-FDG (P = 0.015). In tumors with low Ki-67, 68Ga-RM2 binding was also significantly increased compared to 18F-FDG (P = 0.029). Overall, the binding of 68Ga-RM2 and 18F-FDG displayed an opposite pattern in tumor samples and 68Ga-RM2 binding was significantly higher in tumors that had low 18F-FDG binding (P = 0.021). This inverse correlation was also documented in the few patients in whom a 18F-FDG PET/CT examination before surgery was available. Findings from this in vitro study suggest that GRPR targeting can be an alternative to 18F-FDG imaging in ER+ breast tumors. Moreover, because GRPR antagonists can also be labeled with lutetium-177 this opens new avenues for targeted radionuclide therapy in the subset of patients with progressive metastatic disease following conventional treatments., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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44. Advantages and Limits of Targeted Radionuclide Therapy with Somatostatin Antagonists.
- Author
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Hindié E, Morgat C, Zanotti-Fregonara P, Haissaguerre M, Bordenave L, and Tabarin A
- Subjects
- Indium Radioisotopes, Octreotide analogs & derivatives, Organometallic Compounds, Tissue Distribution, Yttrium Radioisotopes, Receptors, Somatostatin, Somatostatin
- Published
- 2018
- Full Text
- View/download PDF
45. Somatostatin Antagonists for Radioligand Therapy of Nonendocrine Tumors.
- Author
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Hindié E, Zanotti-Fregonara P, and Morgat C
- Subjects
- Humans, Iodine Radioisotopes, Receptors, Somatostatin, Neoplasms, Somatostatin
- Published
- 2018
- Full Text
- View/download PDF
46. Expression of Gastrin-Releasing Peptide Receptor in Breast Cancer and Its Association with Pathologic, Biologic, and Clinical Parameters: A Study of 1,432 Primary Tumors.
- Author
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Morgat C, MacGrogan G, Brouste V, Vélasco V, Sévenet N, Bonnefoi H, Fernandez P, Debled M, and Hindié E
- Subjects
- Adult, Breast Neoplasms diagnosis, Cell Line, Tumor, Female, Humans, Lymphatic Metastasis, Male, Prognosis, Receptors, Estrogen metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, Gene Expression Regulation, Neoplastic, Receptors, Bombesin metabolism
- Abstract
A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. To understand which patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened invasive breast cancers by immunohistochemistry for the presence and intensity of GRPR expression. Methods: We explored a tissue microarray of 1,432 primary breast tumors from patients who underwent surgery between 2000 and 2005 at Institut Bergonié, without prior neoadjuvant treatment. We studied associations between GRPR expression and clinical, pathologic, and biologic parameters. The association between GRPR expression and distant metastasis-free interval was also examined. Results: GRPR overexpression was found in 75.8% of the 1,432 tumors and was most strongly associated with estrogen receptor (ER) positivity (GRPR was high in 83.2% of ER-positive and 12% of ER-negative tumors; P < 0.00001). When molecular subtypes of breast cancer were considered, GRPR was overexpressed in 86.2% of luminal A-like tumors, 70.5% of luminal B-like human epidermal growth factor receptor 2 (HER2)-negative tumors, 82.8% of luminal B-like HER2-positive tumors, 21.3% of HER2-enriched tumors, and 7.8% of triple-negative tumors. Importantly, when breast tumors overexpressed GRPR, high GRPR expression was also found in metastatic lymph nodes in 94.6% of cases. Primary tumors with high GRPR expression were associated with lower risk of distant metastases at follow-up in univariate analysis (Log-rank P = 0.0084) but not in multivariate analysis. Hence, the prognostic impact of GRPR was lost when examined within specific molecular subtypes. Conclusion: Because GRPR is overexpressed in a high percentage of ER-positive tumors, GRPR targeting offers wide perspectives for imaging and treatment in patients with ER-positive breast cancer, using recently developed radiolabeled GRPR ligands., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)
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- 2017
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47. Predicting the outcome of peptide receptor radionuclide therapy in neuroendocrine tumors: the importance of dual-tracer imaging.
- Author
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Zanotti-Fregonara P, Morgat C, Champion C, and Hindié E
- Subjects
- Humans, Octreotide, Radioisotopes, Radiopharmaceuticals, Receptors, Somatostatin, Neuroendocrine Tumors, Receptors, Peptide
- Published
- 2017
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48. Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1.
- Author
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Morgat C, Vélayoudom-Céphise FL, Schwartz P, Guyot M, Gaye D, Vimont D, Schulz J, Mazère J, Nunes ML, Smith D, Hindié E, Fernandez P, and Tabarin A
- Subjects
- Adult, Aged, Duodenum, Female, Humans, Male, Middle Aged, Multiple Endocrine Neoplasia Type 1 complications, Neuroendocrine Tumors complications, Neuroendocrine Tumors diagnostic imaging, Octreotide analogs & derivatives, Organometallic Compounds, Pancreatic Neoplasms complications, Pancreatic Neoplasms diagnostic imaging, Positron Emission Tomography Computed Tomography
- Abstract
Context: Somatostatin receptor scintigraphy with (111)In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with (68)Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1., Purpose: To compare the performances of (68)Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1., Design and Setting: Single-institution prospective comparative study, Patients and Methods: Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, (18)F-2-fluoro-deoxy-D-glucose ((18)F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis., Results: The sensitivity of (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on (68)Ga-DOTA-TOC PET/CT. (68)Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p < 0.03). False negatives of (68)Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and (18)F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with (68)Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS., Conclusions: Owing to higher diagnostic performance, (68)Ga-DOTA-TOC PET/CT (or alternative (68)Ga-labeled somatostatin analogues) should replace (111)In-pentetreotide in the investigation of MEN1 patients.
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- 2016
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49. Comparison between Three Promising ß-emitting Radionuclides, (67)Cu, (47)Sc and (161)Tb, with Emphasis on Doses Delivered to Minimal Residual Disease.
- Author
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Champion C, Quinto MA, Morgat C, Zanotti-Fregonara P, and Hindié E
- Subjects
- Computer Simulation, Copper Radioisotopes pharmacology, Scandium pharmacology, Terbium pharmacology, Neoplasm, Residual radiotherapy, Neoplasms radiotherapy, Radioisotopes pharmacology
- Abstract
Purpose: Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy β(-) emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of (67)Cu, (47)Sc and (161)Tb to irradiate small tumors., Methods: The absorbed dose deriving from a homogeneous distribution of (67)Cu, (47)Sc or (161)Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including β(-) spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm(3), which would result in a dose of 160 Gy if totally absorbed., Results: The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, (161)Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with (67)Cu, 14.8 Gy with (47)Sc and 44.5 Gy with (161)Tb. Auger and conversion electrons accounted for 71% of (161)Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by (161)Tb was 4.1 times higher than that from (67)Cu and 8.1 times that from (47)Sc., Conclusion: (161)Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy β(-) emission and low-energy conversion and Auger electrons. Therefore (161)Tb might be a better candidate than (67)Cu and (47)Sc for treating minimal residual disease in a clinical setting.
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- 2016
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50. Dose Deposits from 90Y, 177Lu, 111In, and 161Tb in Micrometastases of Various Sizes: Implications for Radiopharmaceutical Therapy.
- Author
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Hindié E, Zanotti-Fregonara P, Quinto MA, Morgat C, and Champion C
- Subjects
- Beta Particles therapeutic use, Humans, Indium Radioisotopes therapeutic use, Lutetium therapeutic use, Monte Carlo Method, Radiotherapy Dosage, Terbium therapeutic use, Yttrium Radioisotopes therapeutic use, Neoplasm Micrometastasis pathology, Neoplasm Micrometastasis radiotherapy, Radiation Dosage, Radiopharmaceuticals therapeutic use, Tumor Burden radiation effects
- Abstract
Unlabelled: Radiopharmaceutical therapy, traditionally limited to refractory metastatic cancer, is being increasingly used at earlier stages, such as for treating minimal residual disease. The aim of this study was to compare the effectiveness of (90)Y, (177)Lu, (111)In, and (161)Tb at irradiating micrometastases. (90)Y and (177)Lu are widely used β(-)-emitting radionuclides. (161)Tb is a medium-energy β(-) radionuclide that is similar to (177)Lu but emits a higher percentage of conversion and Auger electrons. (111)In emits γ-photons and conversion and Auger electrons., Methods: We used the Monte Carlo code CELLDOSE to assess electron doses from a uniform distribution of (90)Y, (177)Lu, (111)In, or (161)Tb in spheres with diameters ranging from 10 mm to 10 μm. Because these isotopes differ in electron energy per decay, the doses were compared assuming that 1 MeV was released per μm(3), which would result in 160 Gy if totally absorbed., Results: In a 10-mm sphere, the doses delivered by (90)Y, (177)Lu, (111)In, and (161)Tb were 96.5, 152, 153, and 152 Gy, respectively. The doses decreased along with the decrease in sphere size, and more abruptly so for (90)Y. In a 100-μm metastasis, the dose delivered by (90)Y was only 1.36 Gy, compared with 24.5 Gy for (177)Lu, 38.9 Gy for (111)In, and 44.5 Gy for (161)Tb. In cell-sized spheres, the dose delivered by (111)In and (161)Tb was higher than that of (177)Lu. For instance, in a 10-μm cell, (177)Lu delivered 3.92 Gy, compared with 22.8 Gy for (111)In and 14.1 Gy for (161)Tb., Conclusion: (177)Lu, (111)In, and (161)Tb might be more appropriate than (90)Y for treating minimal residual disease. (161)Tb is a promising radionuclide because it combines the advantages of a medium-energy β(-) emission with those of Auger electrons and emits fewer photons than (111)In., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
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