Kidney Dosimetry in<sup>177</sup>Lu and<sup>90</sup>Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors

Guerriero, Francesca; Ferrari, Mahila; Botta, Francesca; Fioroni, Federica; Grassi, Elisa; Versari, Annibale; Sarnelli, Anna; Pacilio, Massimiliano; Amato, Ernesto; Strigari, Lidia; Bodei, Lisa; Paganelli, Giovanni; Iori, Mauro; Pedroli, G.; Cremonesi, Marta

doi:10.1155/2013/935351

Cited by 89 publications

(73 citation statements)

References 24 publications

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“…Planar imaging, however, is known to have inherent limitations regarding the accuracy of activity quantification (17). As a result, an increasing number of clinical dosimetry protocols currently include 177 Lu SPECT/CT imaging studies (15,(17)(18)(19) because of their superior accuracy. Comparisons of renal dose estimates in 177 Lu-DOTATATE PRRT based on planar imaging and SPECT/CT, for example, have been reported (17,20) and are summarized in Cremonesi et al (21).…”

mentioning

confidence: 99%

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative ¹⁷⁷Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

et al. 2015

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The accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet no. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on 177 Lu (lutetium) and its application in radiopharmaceutical therapy. Theradi onuclide 177 Lu (lutetium) has been proven useful in several targeted radionuclide therapies because of its favorable decay characteristics and the possibility of reliable labeling of biomolecules used for tumor targeting. Initially, 177 Lu was used in a colloidal form for interstitial injections for sterilization of peritumoral lymph nodes (1). A second important clinical application of 177 Lu has been for peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE and other structurally related peptides. The PRRT use in treatment of neuroendocrine tumors (NETs) is motivated by the fact that the carrier peptide, octreotate, shows highaffinity binding to somatostatin receptors, which are overexpressed on the cell surface of many NETs (2-6). Furthermore, 177 Lu has been used in radioimmunotherapy clinical trials to label different kinds of monoclonal antibodies (7-15).There is a growing body of evidence that radionuclide therapy should follow patient-specific planning protocols, similar to those that are being routinely used in external-beam radiation therapy. Recent literature reviews show correlations between absorbed dose and tumor response as well as normal-tissue toxicity (16). Such correlations indicate that treatments should be based on personalized dosimetry, aiming to deliver therapeutically effective absorbed doses to tumors, while keeping doses to organs at risk below the threshold levels for deterministic adverse effects. In clinical PRRT studies, the primary adverse effects have been mainly renal and hematologic toxicities (2,6).Although several studies have reported estimates of absorbed doses (4,7-9,12) for 177 Lu-DOTATATE PRRT and 177 Lu radioimmunotherapy, most of these estimates have been based on planar imaging and conjugate-view activity quantification. Planar imaging, however, is known to have inherent limitations regarding the accuracy of activity quantification (17). As a result, an increasing number of clinical dosimetry protocols currently include 177 Lu SPECT/CT imaging studies (15,(17)(18)(19) because of their superior accuracy. Comparisons of renal dose estimates in 177 Lu-DOTATATE PRRT based on planar imaging and SPECT/CT, for example, have been reported (17,20) and are summarized in Cremonesi et al. (21).This document presents a set of guidelines outlining data acquisition protocols and image reconstruction techniques that are recommended for quantitative 177 Lu SPECT imaging. The guidelines are...

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confidence: 99%

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative ¹⁷⁷Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

et al. 2015

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“…The choice of 111 In or 86 Y for theranostics involves consideration of the advantages and drawbacks of both radionuclides, among which are the lower resolution with 111 In and the insufficient time interval for data collection (;1 d) with 86 Y because of its physical half-life (14.7 h); the latter represents a limit for estimation of the absorbed dose to the kidney (33,48). In any case, the use of 111 In and 86 Y is supported by the fact that extrapolation from both provides reasonably similar estimates for 90 Y.…”

Section: Prrt With 90 Ymentioning

confidence: 99%

“…Moreover, because normal organs (typically liver and spleen but sometimes also kidneys) and tumors may show an uptake phase for more than 24 h, accurate biokinetics and related areas under the time-activity curves cannot be assessed appropriately (48).…”

Section: Prrt With 90 Ymentioning

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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“…Time sampling is also very variable, and this is known to markedly impact the determination of cumulated activities 43 . Even for 3D approaches, protocols can hardly be compared.…”

Section: Internal Dosimetrymentioning

confidence: 99%

Application and Dosimetric Requirements for Gallium-68–labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors

et al. 2015

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Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having a more favorable outcome than G3 ones (also called carcinoma). GEP-NET patients need highly individualized interdisciplinary evaluations and treatment. New treatment options have become available (i.e., sunitinib, mTOR inhibitors) with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using 90Y or 177Lu-labeled somatostatin analogs has also shown promise in the treatment of advanced progressive NETs but randomized clinical trials comparing with other modalities are still lacking. SST-targeting represents the essence of theranostics. 68Ga-DOTA-SSTa can be used as companion imaging agents to assist in such a radionuclide therapy selection. 68Ga-DOTA-SSTa PET/CT might also provide critical information for prognosis, tumor response assessement to PRRT, and internal dosimetry. It is also expected that the development of novel receptor-targeting radiopharmaceuticals will contribute to the development of molecular-based personalized medicine approaches.

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Kidney Dosimetry in¹⁷⁷Lu and⁹⁰Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors

Cited by 89 publications

References 24 publications

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative ¹⁷⁷Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative ¹⁷⁷Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

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

Application and Dosimetric Requirements for Gallium-68–labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors

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Kidney Dosimetry in177Lu and90Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors

Cited by 89 publications

References 24 publications

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

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

Application and Dosimetric Requirements for Gallium-68–labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors

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Kidney Dosimetry in¹⁷⁷Lu and⁹⁰Y Peptide Receptor Radionuclide Therapy: Influence of Image Timing, Time-Activity Integration Method, and Risk Factors

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative ¹⁷⁷Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative ¹⁷⁷Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy