The NUKDOS software for treatment planning in molecular radiotherapy

Kletting, Peter; Schimmel, S.; Hänscheid, Heribert; Luster, Markus; Fernández, María Soledad; Noßke, D.; Laßmann, Michael; Glatting, Gerhard

doi:10.1016/j.zemedi.2015.01.001

Cited by 49 publications

(46 citation statements)

References 28 publications

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“…For the first measurement series (N1), the reference time was the start of the infusion. To obtain the time-activity data, ULMDOS (13) and NUKDOS (14), which contain background correction, self-attenuation, and scatter corrections according to MIRD pamphlet 16 (15) for conjugate view counting, were used. Regions of interest were drawn for 1 (for patients 2, 4, and 5) or 2 tumor sites, liver, left kidney, spleen, and total body.…”

Section: Patients/datamentioning

confidence: 99%

Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy

et al. 2015

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In peptide receptor radionuclide therapy with 90 Y-labeled DOTATATE, the kidney absorbed dose limits the maximum amount of total activity that can be safely administered in many patients. A higher tumor-to-kidney absorbed dose ratio might be achieved by optimizing the amount of injected peptide and activity, as recent studies have shown different degrees of receptor saturation for normal tissue and tumor. The aim of this work was to develop and implement a modeling method for treatment planning to determine the optimal combination of peptide amount and pertaining therapeutic activity for each patient. Methods: A whole-body physiologically based pharmacokinetic (PBPK) model was developed. General physiologic parameters were taken from the literature. Individual model parameters were fitted to a series (n 5 12) of planar γ-camera and serum measurements ( 111 In-DOTATATE) of patients with meningioma or neuroendocrine tumors (NETs). Using the PBPK model and the individually estimated parameters, we determined the tumor, liver, spleen, and red marrow biologically effective doses (BEDs) for a maximal kidney BED (20 Gy 2.5 ) for different peptide amounts and activities. The optimal combination of peptide amount and activity for maximal tumor BED, considering the additional constraint of a red marrow BED less than 1 Gy 15 , was individually quantified. Results: The PBPK model describes the biokinetic data well considering the criteria of visual inspection, the coefficients of determination, the relative standard errors (,50%), and the correlation of the parameters (,0.8). All fitted parameters were in a physiologically reasonable range but varied considerably between patients, especially tumor perfusion (meningioma, 0.1-1 mLÁg −1 Ámin −1 , and NETs, 0.02-1 mLÁg −1 Ámin −1 ) and receptor density (meningioma, 5-34 nmolÁL −1 , and NETs, 7-35 nmolÁL −1 ). Using the proposed method, we identified the optimal amount and pertaining activity to be 76 ± 46 nmol (118 ± 71 μg) and 4.2 ± 1.8 GBq for meningioma and 87 ± 50 nmol (135 ± 78 μg) and 5.1 ± 2.8 GBq for NET patients. Conclusion: The presented work suggests that to achieve higher efficacy and safety for 90 Y-DOATATE therapy, both the administered amount of peptide and the activity should be optimized in treatment planning using the proposed method. This approach could also be adapted for therapy with other peptides.

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Section: Patients/datamentioning

confidence: 99%

Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy

et al. 2015

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“…At present, voxelbased S values are frequently used for patient-specific dose calculations. An example of the type of calculation that uses voxel-based S values is the NUKDOS software (25).…”

Section: Internal Dosimetry Dosimetry In Nuclear Medicinementioning

confidence: 99%

Individualized Dosimetry for Theranostics: Necessary, Nice to Have, or Counterproductive?

2017

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In 2005, the term theragnostics (theranostics) was introduced for describing the use of imaging for therapy planning in radiation oncology. In nuclear medicine, this expression describes the use of tracers for predicting the absorbed doses in molecular radiotherapy and, thus, the safety and efficacy of a treatment. At present, the most successful groups of isotopes for this purpose are 123 In2005,t he term theragnostics (theranostics) was first used for describing the use of imaging for therapy planning in radiation oncology. It is defined as the use of information from medical images to determine the optimal therapy for an individual patient (1). In nuclear medicine, this expression describes the use of tracers for predicting the absorbed doses in molecular radiotherapy and, thus, the safety and efficacy of a treatment. At present, the most successful groups of isotopes for theranostics are 123 I/ 124 I/ 131 I (2), 68 Ga/ 177 Lu, and 111 In/ 86 Y/ 90 Y (3).In recent years, numerous reports providing pre-and peritherapeutic dosimetry data for molecular radiotherapies with 131 I-sodium iodide (4-8) and 177 Lu-labeled (9-16) and 90 Y-labeled (13,(17)(18)(19)(20) compounds have been published. The purpose of this review is to introduce the concept of theranostics, present available data on the dosimetry and dose-response relationships of theranostic compounds, and discuss whether individualized dosimetry for theranostics is necessary, nice to have, or counterproductive. Special focus is given to the provision of radioiodine therapy for differentiated thyroid cancer and peptide receptor radionuclide therapy (PRRT) with 177 Luand 90 Y-labeled peptides. INTERNAL DOSIMETRY Dosimetry in Nuclear MedicineThe basic methodology for calculating the absorbed doses from the administration of a radiopharmaceutical was developed by the MIRD Committee (21):Eq. 1 where• Dðr T Þ is the mean absorbed dose to target region r T delivered by the cumulated activity in source region r S .•Ãðr S Þ is the time-integrated activity in source region r S .Ã denotes the total number of radioactive decays (determined by integrating the time-activity curve from time 0 to infinity) occurring within an accumulating organ.Ã is determined by quantitative imaging at several time points after the administration of a radiopharmaceutical for an assessment of organor voxel-specific pharmacokinetics. A proposal for choosing optimal time points is given in MIRD Pamphlet No. 16 (22). • A 0 is the administered activity.•ãðr S Þ is the time-integrated activity coefficient, which is the time-integrated activity divided by the administered activity.• Sðr T )r S Þ is the radionuclide specific absorbed dose rate per unit of activity in target region r T delivered by source region r S (formerly called S value).For calculation of the absorbed dose, therefore, several steps are essential.The first step is to perform quantitative imaging at different time points to assess the activity in the organs of interest over time. The established method for quantitative imagi...

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“…Therefore, the following dosimetric procedures need to be addressed in research:

Development of computational methods for dose distribution calculations based on patient-specific and equipment-specific characteristics for all medical procedures using ionising radiation, including for example CT, interventional and nuclear medicine procedures as well as radiotherapeutic procedures avoiding different dose indicators for different types of procedures in order to get comparable meaningful information about organ doses of individuals.

Development of optimal measurement protocols in nuclear medicine for accurate estimation of absorbed doses using patient-specific and equipment-specific characteristics. Refinement, validation and implementation of new biokinetic models for dosimetry in molecular radiotherapy using for example physiologically based pharmacokinetic (PBPK) models for the individual assessment of biokinetics (13), including uncertainty budgets (14).

Development of methods to estimate or measure the actual delivered radiation dose in radiotherapy.

Development of a unique dose indicator that describes the absorbed dose to organs in order to perform risk assessment.

…”

Section: Research Topicsmentioning

confidence: 99%

“…Refinement, validation and implementation of new biokinetic models for dosimetry in molecular radiotherapy using for example physiologically based pharmacokinetic (PBPK) models for the individual assessment of biokinetics (13), including uncertainty budgets (14). …”

Section: Research Topicsmentioning

confidence: 99%

Common strategic research agenda for radiation protection in medicine

2017

Insights Imaging

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Reflecting the change in funding strategies for European research projects, and the goal to jointly improve medical radiation protection through sustainable research efforts, five medical societies involved in the application of ionising radiation (European Association of Nuclear Medicine, EANM; European Federation of Organizations for Medical Physics. EFOMP; European Federation of Radiographer Societies, EFRS; European Society of Radiology, ESR; European Society for Radiotherapy and Oncology, ESTRO) have identified research areas of common interest and developed this first edition of the Common Strategic Research Agenda (SRA) for medical radiation protection.The research topics considered necessary and most urgent for effective medical care and efficient in terms of radiation protection are summarised in five main themes:Measurement and quantification in the field of medical applications of ionising radiationNormal tissue reactions, radiation-induced morbidity and long-term health problemsOptimisation of radiation exposure and harmonisation of practicesJustification of the use of ionising radiation in medical practiceInfrastructures for quality assurance The SRA is a living document; thus comments and suggestions by all stakeholders in medical radiation protection are welcome and will be dealt with by the European Alliance for Medical Radiation Protection Research (EURAMED) established by the above-mentioned societies.Main messages• Overcome the fragmentation of medical radiation protection research in Europe • Identify research areas of joint interest in the field of medical radiation protection • Improve the use of ionising radiation in medicine • Collect stakeholder feedback and seek consensus • Emphasise importance of clinical translation and evaluation of research results

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The NUKDOS software for treatment planning in molecular radiotherapy

Cited by 49 publications

References 28 publications

Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy

Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy

Individualized Dosimetry for Theranostics: Necessary, Nice to Have, or Counterproductive?

Common strategic research agenda for radiation protection in medicine

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The NUKDOS software for treatment planning in molecular radiotherapy

Cited by 49 publications

References 28 publications

Optimized Peptide Amount and Activity for 90Y-Labeled DOTATATE Therapy

Optimized Peptide Amount and Activity for 90Y-Labeled DOTATATE Therapy

Individualized Dosimetry for Theranostics: Necessary, Nice to Have, or Counterproductive?

Common strategic research agenda for radiation protection in medicine

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Product

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Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy

Optimized Peptide Amount and Activity for ⁹⁰Y-Labeled DOTATATE Therapy