19 results on '"Jiménez-Franco, Luis David"'
Search Results
2. Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC
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Kramer, Vasko, Fernández, René, Lehnert, Wencke, Jiménez-Franco, Luis David, Soza-Ried, Cristian, Eppard, Elisabeth, Ceballos, Matias, Meckel, Marian, Benešová, Martina, Umbricht, Christoph A., Kluge, Andreas, Schibli, Roger, Zhernosekov, Konstantin, Amaral, Horacio, and Müller, Cristina
- Published
- 2021
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3. Performance assessment of the ALBIRA II pre-clinical SPECT S102 system for 99mTc imaging
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Attarwala, Ali Asgar, Hardiansyah, Deni, Romanó, Chiara, Jiménez-Franco, Luis David, Roscher, Mareike, Wängler, Björn, and Glatting, Gerhard
- Published
- 2021
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4. Automated and robust organ segmentation for 3D-based internal dose calculation
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Nazari, Mahmood, Jiménez-Franco, Luis David, Schroeder, Michael, Kluge, Andreas, Bronzel, Marcus, and Kimiaei, Sharok
- Published
- 2021
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5. Modelling the internalisation process of prostate cancer cells for PSMA-specific ligands
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Winter, Gordon, Vogt, Anja, Jiménez-Franco, Luis David, Rinscheid, Andreas, Yousefzadeh-Nowshahr, Elham, Solbach, Christoph, Beer, Ambros J., Glatting, Gerhard, and Kletting, Peter
- Published
- 2019
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6. Evaluation of safety and dosimetry of 177Lu-DOTA-ZOL for therapy of bone metastases.
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Fernández, René, Eppard, Elisabeth, Lehnert, Wencke, Jiménez-Franco, Luis David, Soza-Ried, Cristian, Ceballos, Matías, Ribbeck, Jessica, Kluge, Andreas, Rösch, Frank, Meckel, Marian, Zhernosekov, Konstantin, Kramer, Vasko, and Amaral, Horacio
- Published
- 2021
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- View/download PDF
7. Evaluation of safety and dosimetry of 177Lu-DOTA-ZOL for therapy of bone metastases.
- Author
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Fernández, René, Eppard, Elisabeth, Lehnert, Wencke, Jiménez-Franco, Luis David, Soza-Ried, Cristian, Ceballos, Matías, Ribbeck, Jessica, Kluge, Andreas, Rösch, Frank, Meckel, Marian, Zhernosekov, Konstantin, Kramer, Vasko, and Amaral, Horacio
- Published
- 2021
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8. Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma.
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Merkx, Robin I. J., Lobeek, Daphne, Konijnenberg, Mark, Jiménez-Franco, Luis David, Kluge, Andreas, Oosterwijk, Egbert, Mulders, Peter F.A., and Rijpkema, Mark
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RENAL cell carcinoma ,RADIATION dosimetry ,COMPUTED tomography ,ADVERSE health care events ,INTRAVENOUS therapy - Abstract
Purpose: In this phase I study, we evaluated the safety, biodistribution and dosimetry of [
89 Zr]Zr-DFO-girentuximab (89 Zr-girentuximab) PET/CT imaging in patients with suspicion of clear cell renal cell carcinoma (ccRCC). Methods: Ten eligible patients received an intravenous administration of 37 MBq (± 10%) of89 Zr-girentuximab at mass doses of 5 mg or 10 mg. Safety was evaluated according to the NCI CTCAE (version 4.03). Biodistribution and normal organ dosimetry was performed based on PET/CT images acquired at 0.5, 4, 24, 72 and 168 h post-administration. Additionally, tumour dosimetry was performed in patients with confirmed ccRCC and visible tumour uptake on PET/CT imaging. Results:89 Zr-girentuximab was administered in ten patients as per protocol. No treatment-related adverse events ≥ grade 3 were reported.89 Zr-girentuximab imaging allowed successful differentiation between ccRCC and non-ccRCC lesions in all patients, as confirmed with histological data. Dosimetry analysis using OLINDA/EXM 2.1 showed that the organs receiving the highest doses (mean ± SD) were the liver (1.86 ± 0.40 mGy/MBq), the kidneys (1.50 ± 0.22 mGy/MBq) and the heart wall (1.45 ± 0.19 mGy/MBq), with a mean whole body effective dose of 0.57 ± 0.08 mSv/MBq. Tumour dosimetry was performed in the 6 patients with histologically confirmed ccRCC resulting in a median tumour-absorbed dose of 4.03 mGy/MBq (range 1.90–11.6 mGy/MBq). Conclusions: This study demonstrates that89 Zr-girentuximab is safe and well tolerated for the administered activities and mass doses and allows quantitative assessment of89 Zr-girentuximab PET/CT imaging in patients with suspicion of ccRCC. Trial registration: NCT03556046—14th of June, 2018 [ABSTRACT FROM AUTHOR]- Published
- 2021
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9. Development of a treatment planning algorithm for peptide-receptor radionuclide therapy considering multiple tumour lesions and organs at risk
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Jiménez Franco, Luis David
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610 Medical sciences Medicine ,530 Physics - Abstract
Peptide-receptor radionuclide therapy (PRRT) is a modality of molecular radiotherapy in which patients are administered with radiolabelled peptides targeting peptide-receptors overexpressed in some types of tumours. PRRT has shown promising results in the treatment of tumours with high expression of somatostatin receptors (e.g. neuroendocrine tumours (NETs) and meningioma). However, this therapeutic modality is limited by radiotoxicity in the kidneys and in the red bone marrow (RM). Therefore, to safely apply PRRT to patients, individualised treatment planning is required. Recently, it was shown that individually choosing an optimal combination of radiopharmaceutical amount and activity may lead to higher therapeutic indices (i.e. the ratio between the tumour dose and the dose in the dose-limiting organ). However, some additional features are required during treatment planning to achieve clinical applicability in PRRT: 1. Multiple tumour lesions/metastases need to be considered simultaneously. 2. Multiple potentially dose-limiting organs need to be included. 3. Constraints in the radiopharmaceutical synthesis need to be accounted for. Therefore, the aim of this work was to develop a clinically applicable treatment planning algorithm for PRRT. Furthermore, an in silico (i.e. based on computational simulations) clinical trial was conducted to demonstrate the applicability and advantages of the developed algorithm. The developed algorithm can be applied to patients with multiple metastases by using the developed concept of overall biologically effective dose (oBED). The tumour oBED, as developed in this work, is a biologically effective dose (BED) value representing the total number of killed tumour cells after radiotherapy. Therefore, maximising the tumour oBED during treatment planning will derive plans producing the maximum number of killed tumour cells among the considered tumour lesions. Additionally, the developed algorithm simultaneously incorporates multiple potentially dose-limiting organs and considers the maximum molar activity (i.e. the ratio between activity and amount) which can be achieved during the radiopharmaceutical synthesis. Thus, the developed treatment planning algorithm derives plans which maximise the total number of tumour cells within tolerated dose values for multiple organs at risk (OARs) while considering the maximum achievable molar activity in the radiopharmaceutical synthesis. An in silico clinical trial was conducted for 177Lu-DOTATATE using nine virtual patients (i.e. a physiologically-based pharmacokinetic (PBPK) model fitted to measured patient data). In this trial, plans individually derived with the developed algorithm were compared with the routinely delivered plan for 177Lu-DOTATATE. Comparison between the optimal plans and the typical plan showed that the optimal plans can produce much higher tumour control probability (oTCP) than the typical plan. Therefore, based on the expected advantages, the developed algorithm is proposed for clinical validation and potential future implementation.
- Published
- 2018
10. Performance assessment of the ALBIRA II pre-clinical SPECT S102 system for 99mTc imaging.
- Author
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Attarwala, Ali Asgar, Hardiansyah, Deni, Romanó, Chiara, Jiménez-Franco, Luis David, Roscher, Mareike, Wängler, Björn, and Glatting, Gerhard
- Abstract
Objective: The performance characteristics of the SPECT sub-system S102 of the ALBIRA II PET/SPECT/CT are analyzed for the 80 mm field of view (FOV) to evaluate the potential in-vivo imaging in rats, based on measurements of the system response for the commonly used Technetium-99 m (99mTc) in small animal imaging.Methods: The ALBIRA II tri-modal µPET/SPECT/CT pre-clinical system (Bruker BioSpin, Ettlingen, Germany) was used. The SPECT modality is made up of two opposite gamma cameras (Version S102) with Sodium doped Cesium Iodide (CsI(Na)) single continuous crystal detectors coupled to position-sensitive photomultipliers (PSPMTs). Imaging was performed with the NEMA NU-4 image quality phantom (Data Spectrum Corporation, Durham, USA). Measurements were performed with a starting activity concentration of 4.76 MBq/mL 99mTc. An energy window of 20% at 140 keV was selected in this study. The system offers a 20 mm, 40 mm, 60 mm and an 80 mm field of view (FOV) and in this study the 80 mm FOV was used for all the acquisitions. The data were reconstructed with an ordered subset expectation maximization (OSEM) algorithm. Sensitivity, spatial resolution, count rate linearity, convergence of the algorithm and the recovery coefficients (RC) were analyzed. All analyses were performed with PMOD and MATLAB software.Results: The sensitivities measured at the center of the 80 mm FOV with the point source were 23.1 ± 0.3 cps/MBq (single pinhole SPH) and 105.6 ± 5.5 cps/MBq (multi pinhole MPH). The values for the axial, tangential and radial full width at half maximum (FWHM) were 2.51, 2.54, and 2.55 mm with SPH and 2.35, 2.44 and 2.32 mm with MPH, respectively. The corresponding RC values for the 5 mm, 4 mm, 3 mm and 2 mm rods were 0.60 ± 0.28, 0.61 ± 0.24, 0.29 ± 0.11 and 0.20 ± 0.06 with SPH and 0.56 ± 0.20, 0.50 ± 0.18, 0.38 ± 0.09 and 0.23 ± 0.06 with MPH. To obtain quantitative imaging data, the image reconstructions should be performed with 12 iterations.Conclusion: The ALBIRA II preclinical SPECT sub-system S102 has a favorable sensitivity and spatial resolution for the 80 mm FOV setting for both the SPH and MPH configurations and is a valuable tool for small animal imaging. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
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11. FAPI-74 PET/CT Using Either 18F-AlF or Cold-kit 68Ga-labeling: Biodistribution, Radiation Dosimetry and Tumor Delineation in Lung Cancer Patients.
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Giesel, Frederik L., Adeberg, Sebastian, Syed, Mustafa, Lindner, Thomas, Jiménez-Franco, Luis David, Mavriopoulou, Eleni, Staudinger, Fabian, Tonndorf-Martini, Eric, Regnery, Sebastian, Rieken, Stefan, El Shafie, Rami, Röhrich, Manuel, Flechsig, Paul, Kluge, Andreas, Altmann, Annette, Debus, Jürgen, Haberkorn, Uwe, and Kratochwil, Clemens
- Published
- 2020
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12. FAPI-74 PET/CT Using Either 18F-AlF or Cold-kit 68Ga-labeling: Biodistribution, Radiation Dosimetry and Tumor Delineation in Lung Cancer Patients.
- Author
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Giesel, Frederik L., Adeberg, Sebastian, Syed, Mustafa, Lindner, Thomas, Jiménez-Franco, Luis David, Mavriopoulou, Eleni, Staudinger, Fabian, Tonndorf-Martini, Eric, Regnery, Sebastian, Rieken, Stefan, Shafie, Rami El, Röhrich, Manuel, Flechsig, Paul, Kluge, Andreas, Altmann, Annette, Debus, Jürgen, Haberkorn, Uwe, and Kratochwil, Clemens
- Published
- 2020
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13. Effect of tumor perfusion and receptor density on tumor control probability in 177Lu-DOTATATE therapy: An in silico analysis for standard and optimized treatment.
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Jiménez-Franco, Luis David, Glatting, Gerhard, Prasad, Vikas, Weber, Wolfgang A., Beer, Ambros J., and Kletting, Peter
- Published
- 2020
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14. FAPI-74 PET/CT Using Either 18F-AlF or Cold-kit 68Ga-labeling: Biodistribution, Radiation Dosimetry and Tumor Delineation in Lung Cancer Patients.
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Giesel, Frederik L., Adeberg, Sebastian, Syed, Mustafa, Lindner, Thomas, Jiménez-Franco, Luis David, Mavriopoulou, Eleni, Staudinger, Fabian, Tonndorf-Martini, Eric, Regnery, Sebastian, Rieken, Stefan, El Shafie, Rami, Röhrich, Manuel, Flechsig, Paul, Kluge, Andreas, Altmann, Annette, Debus, Jürgen, Haberkorn, Uwe, and Kratochwil, Clemens
- Published
- 2020
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- View/download PDF
15. Treatment planning algorithm for peptide receptor radionuclide therapy considering multiple tumor lesions and organs at risk.
- Author
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Jiménez‐Franco, Luis David, Kletting, Peter, Beer, Ambros J., and Glatting, Gerhard
- Subjects
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TUMOR treatment , *RADIOTHERAPY treatment planning , *ALGORITHMS , *PEPTIDE receptors , *NUCLEAR medicine , *CANCER radiotherapy , *SOMATOSTATIN , *TUMOR risk factors - Abstract
Purpose: Peptide receptor radionuclide therapy (PRRT) has shown promising results in the treatment of tumors with high expression of somatostatin receptors such as neuroendocrine tumors (NETs) and meningioma. However, PRRT potentially produces high renal and red marrow (RM) toxicity, the kidneys usually being the dose‐limiting organ. Previously, it was shown that an improved therapeutic index can be achieved by choosing an optimal combination of injected activity and peptide molar amount. The aim of this work was to develop a clinically applicable algorithm for treatment planning in PRRT. To demonstrate the applicability and possible advantages of the algorithm thus developed, an in silico clinical trial applying the algorithm to 177Lu‐DOTATATE therapy in nine virtual patients was conducted. Methods: An algorithm for treatment planning in PRRT was developed, which simultaneously considers multiple tumor lesions, maximum tolerated biologically effective doses (BEDs) for multiple organs at risk (OARs) and a maximum achievable molar activity. The algorithm, subject to the abovementioned constraints, aims at maximizing the total number of killed tumor cells in the considered lesions/metastases. An in silico clinical trial was conducted with nine virtual patients. For each virtual patient, simulations increasing the molar dose of 177Lu‐DOTATATE from 2 to 2048 nmol by factors of 2 5 were performed. Maximum tolerated BEDs per cycle for the kidneys (10 Gy2.5) and for the RM (0.5 Gy15) were defined based on a planned total treatment of four cycles. A maximum achievable molar activity of 420 MBq/nmol was assumed. Optimal combinations of molar dose and activity were determined by applying the developed algorithm. For comparison, simulations for a typical plan with 177Lu‐DOTATATE (7.4 GBq, 265 nmol) were performed and BEDs for the OARs and for individual tumor lesions were calculated. Furthermore, to determine treatment efficacy, overall tumor control probability (oTCP) values after a four‐cycle treatment were estimated for the optimal and typical plans. Results: The conducted in silico clinical trial yielded optimal molar doses and activities ranging from 24 to 512 nmol and from 6 to 30 GBq, respectively. Tumor BEDs ranged from 2 to 107 Gy10 and from 1 to 65 Gy10 for the optimal and typical plans, respectively. The estimated oTCP values showed that the optimal plans may produce adequate tumor control in six of the nine virtual patients after four cycles of 177Lu‐DOTATATE while the typical plan may be sufficient in only two virtual patients. Conclusions: The algorithm presented can derive plans with higher tumor control than the typically delivered plan. Therefore, we propose this algorithm for clinical validation and possibly future implementation in treatment planning in molecular radiotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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16. Evaluation of Safety and Dosimetry of 177 Lu-DOTA-ZOL for Therapy of Bone Metastases.
- Author
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Fernández R, Eppard E, Lehnert W, Jiménez-Franco LD, Soza-Ried C, Ceballos M, Ribbeck J, Kluge A, Rösch F, Meckel M, Zhernosekov K, Kramer V, and Amaral H
- Subjects
- Humans, Male, Aged, Middle Aged, Diphosphonates therapeutic use, Safety, Imidazoles therapeutic use, Radiopharmaceuticals therapeutic use, Aged, 80 and over, Organometallic Compounds therapeutic use, Prostatic Neoplasms, Castration-Resistant radiotherapy, Prostatic Neoplasms, Castration-Resistant pathology, Radioisotopes therapeutic use, Lutetium, Bone Neoplasms secondary, Bone Neoplasms radiotherapy, Bone Neoplasms diagnostic imaging, Radiometry, Single Photon Emission Computed Tomography Computed Tomography
- Abstract
Palliative treatment of bone metastasis using radiolabeled bisphosphonates is a well-known concept proven to be safe and effective. A new therapeutic radiopharmaceutical for bone metastasis is
177 Lu-DOTA-zoledronic acid (177 Lu-DOTA-ZOL). In this study, the safety and dosimetry of a single therapeutic dose of177 Lu-DOTA-ZOL were evaluated on the basis of a series of SPECT/CT images and blood samples. Methods: Nine patients with exclusive bone metastases from metastatic castration-resistant prostate cancer (mCRPC) (70.8 ± 8.4 y) and progression under conventional therapies participated in this prospective study. After receiving 5,780 ± 329 MBq177 Lu-DOTA-ZOL, patients underwent 3-dimensional whole-body SPECT/CT imaging and venous blood sampling over 7 d. Dosimetric evaluation was performed for main organs and tumor lesions. Safety was assessed by blood biomarkers. Results:177 Lu-DOTA-ZOL showed fast uptake and high retention in bone lesions and fast clearance from the bloodstream in all patients. The average retention in tumor lesions was 0.02% injected activity per gram at 6 h after injection and approximately 0.01% at 170 h after injection. In this cohort, the average absorbed doses in bone tumor lesions, kidneys, red bone marrow, and bone surfaces were 4.21, 0.17, 0.36, and 1.19 Gy/GBq, respectively. The red marrow was found to be the dose-limiting organ for all patients. A median maximum tolerated injected activity of 6.0 GBq may exceed the defined threshold of 2 Gy for the red bone marrow in individual patients (4/8). Conclusion:177 Lu-DOTA-ZOL is safe and has a favorable therapeutic index compared with other radiopharmaceuticals used in the treatment of osteoblastic bone metastases. Personalized dosimetry, however, should be considered to avoid severe hematotoxicity for individual patients., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2021
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17. FAPI-74 PET/CT Using Either 18 F-AlF or Cold-Kit 68 Ga Labeling: Biodistribution, Radiation Dosimetry, and Tumor Delineation in Lung Cancer Patients.
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Giesel FL, Adeberg S, Syed M, Lindner T, Jiménez-Franco LD, Mavriopoulou E, Staudinger F, Tonndorf-Martini E, Regnery S, Rieken S, El Shafie R, Röhrich M, Flechsig P, Kluge A, Altmann A, Debus J, Haberkorn U, and Kratochwil C
- Subjects
- Aged, Biological Transport, Female, Humans, Isotope Labeling, Male, Middle Aged, Radiometry, Temperature, Tissue Distribution, Aluminum Compounds chemistry, Fluorides chemistry, Gallium Radioisotopes chemistry, Lung Neoplasms diagnostic imaging, Lung Neoplasms metabolism, Positron Emission Tomography Computed Tomography
- Abstract
68 Ga-fibroblast activation protein inhibitors (FAPIs) 2, 4, and 46 have already been proposed as promising PET tracers. However, the short half-life of68 Ga (68 min) creates problems with manufacture and delivery.18 F (half-life, 110 min) labeling would result in a more practical large-scale production, and a cold-kit formulation would improve the spontaneous availability. The NOTA chelator ligand FAPI-74 can be labeled with both18 F-AlF and68 Ga. Here, we describe the in vivo evaluation of18 F-FAPI-74 and a proof of mechanism for68 Ga-FAPI-74 labeled at ambient temperature. Methods: In 10 patients with lung cancer, PET scans were acquired at 10 min, 1 h, and 3 h after administration of 259 ± 26 MBq of18 F-FAPI-74. Physiologic biodistribution and tumor uptake were semiquantitatively evaluated on the basis of SUV at each time point. Absorbed doses were evaluated using OLINDA/EXM, version 1.1, and QDOSE dosimetry software with the dose calculator IDAC-Dose, version 2.1. Identical methods were used to evaluate one examination after injection of 263 MBq of68 Ga-FAPI-74. Results: The highest contrast was achieved in primary tumors, lymph nodes, and distant metastases at 1 h after injection, with an SUVmax of more than 10. The effective dose per a 100-MBq administered activity of18 F-FAPI-74 was 1.4 ± 0.2 mSv, and for68 Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic18 F-FAPI-74 PET scan is even lower than that of PET scans with18 F-FDG and other18 F tracers;68 Ga-FAPI-74 is comparable to other68 Ga ligands. FAPI PET/CT supported target volume definition for guiding radiotherapy. Conclusion: The high contrast and low radiation burden of FAPI-74 PET/CT favor multiple clinical applications. Centralized large-scale production of18 F-FAPI-74 or decentralized cold-kit labeling of68 Ga-FAPI-74 allows flexible routine use., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2021
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18. Effect of Tumor Perfusion and Receptor Density on Tumor Control Probability in 177 Lu-DOTATATE Therapy: An In Silico Analysis for Standard and Optimized Treatment.
- Author
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Jiménez-Franco LD, Glatting G, Prasad V, Weber WA, Beer AJ, and Kletting P
- Subjects
- Humans, Meningeal Neoplasms blood supply, Meningeal Neoplasms metabolism, Meningeal Neoplasms pathology, Meningioma blood supply, Meningioma metabolism, Meningioma pathology, Models, Biological, Neuroendocrine Tumors blood supply, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors pathology, Octreotide therapeutic use, Probability, Reference Standards, Tumor Burden radiation effects, Blood Circulation radiation effects, Computer Simulation, Meningeal Neoplasms radiotherapy, Meningioma radiotherapy, Neuroendocrine Tumors radiotherapy, Octreotide analogs & derivatives, Organometallic Compounds therapeutic use, Receptors, Somatostatin metabolism
- Abstract
The aim of this work was to determine a minimal tumor perfusion and receptor density for
177 Lu-DOTATATE therapy using physiologically based pharmacokinetic (PBPK) modeling considering, first, a desired tumor control probability (TCP) of 99% and, second, a maximal tolerated biologically effective dose (BEDmax ) for organs at risk (OARs) in the treatment of neuroendocrine tumors and meningioma. Methods: A recently developed PBPK model was used. Nine virtual patients (i.e., individualized PBPK models) were used to perform simulations of pharmacokinetics for different combinations of perfusion (0.001-0.1 mL/g/min) and receptor density (1-100 nmol/L). The TCP for each combination was determined for 3 different treatment strategies: a standard treatment (4 cycles of 7.4 GBq and 105 nmol), a treatment maximizing the number of cycles based on BEDmax for red marrow and kidneys, and a treatment having 4 cycles with optimized ligand amount and activity. The red marrow and the kidneys (BEDmax of 2 Gy15 and 40 Gy2.5 , respectively) were assumed to be OARs. Additionally, the influence of varying glomerular filtration rates, kidney somatostatin receptor densities, tumor volumes, and release rates was investigated. Results: To achieve a TCP of at least 99% in the standard treatment, a minimal tumor perfusion of 0.036 ± 0.023 mL/g/min and receptor density of 34 ± 20 nmol/L were determined for the 9 virtual patients. With optimization of the number of cycles, the minimum values for perfusion and receptor density were considerably lower, at 0.022 ± 0.012 mL/g/min and 21 ± 11 nmol/L, respectively. However, even better results (perfusion, 0.018 ± 0.009 mL/g/min; receptor density, 18 ± 10 nmol/L) were obtained for strategy 3. The release rate of177 Lu (or labeled metabolites) from tumor cells had the strongest effect on the minimal perfusion and receptor density for standard and optimized treatments. Conclusion: PBPK modeling and simulations represent an elegant approach to individually determine the minimal tumor perfusion and minimal receptor density required to achieve an adequate TCP. This computational method can be used in the radiopharmaceutical development process for ligand and target selection for specific types of tumors. In addition, this method could be used to optimize clinical trials., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2021
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19. MITIGATE-NeoBOMB1, a Phase I/IIa Study to Evaluate Safety, Pharmacokinetics, and Preliminary Imaging of 68 Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.
- Author
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Gruber L, Jiménez-Franco LD, Decristoforo C, Uprimny C, Glatting G, Hohenberger P, Schoenberg SO, Reindl W, Orlandi F, Mariani M, Jaschke W, and Virgolini I
- Subjects
- Aged, Aged, 80 and over, Bombesin adverse effects, Bombesin pharmacology, Female, Gastrointestinal Stromal Tumors metabolism, Humans, Male, Middle Aged, Neoplasm Metastasis, Radiometry, Tissue Distribution, Bombesin chemistry, Bombesin pharmacokinetics, Gallium Radioisotopes chemistry, Gastrointestinal Stromal Tumors diagnostic imaging, Gastrointestinal Stromal Tumors pathology, Receptors, Bombesin antagonists & inhibitors, Safety
- Abstract
Gastrin-releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a
68 Ga-labeled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumors ('MITIGATE') (grant agreement no. 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Methods: The main objectives were evaluation of safety, biodistribution, dosimetry, and preliminary tumor targeting of68 Ga-NeoBOMB1 in patients with advanced tyrosine-kinase inhibitors-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary lesion or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included.68 Ga-NeoBOMB1 was prepared using a kit procedure with a licensed68 Ge/68 Ga generator.68 Ga-NeoBOMB1 (3 MBq/kg of body weight) was injected intravenously, and safety parameters were assessed. PET/CT included dynamic imaging at 5, 11, and 19 min as well as static imaging at 1, 2, and 3-4 h after injection for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetic analysis. Tumor targeting was assessed on a per-lesion and per-patient basis. Results:68 Ga-NeoBOMB1 (50 μg) was prepared with high radiochemical purity (yield > 97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 wk. Dosimetry calculations revealed a mean effective dose of 0.029 ± 0.06 mSv/MBq, with the highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7% ± 5.4% of injected dose 4 h after injection). Plasma metabolite analyses revealed high stability; metabolites were detected only in the urine. In 3 patients, a significant uptake with increasing maximum SUVs (SUVmax at 2 h after injection: 4.3-25.9) over time was found in tumor lesions. Conclusion: This phase I/IIa study provides safety data for68 Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging, and absorbed dose estimates are comparable to those of other68 Ga-labeled radiopharmaceuticals used in clinical routine., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2020
- Full Text
- View/download PDF
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