[177Lu‐DOTA0‐Tyr3]‐Octreotate Treatment in Patients with Disseminated Gastroenteropancreatic Neuroendocrine Tumors: The Value of Measuring Absorbed Dose to the Kidney

Swärd, Christina; Bernhardt, Peter; Ahlman, Håkan; Wängberg, Bo; Forssell-Aronsson, Eva; Larsson, Maria; Svensson, Johanna; Rossi-Norrlund, Rauni; Kölby, Lars

doi:10.1007/s00268-009-0387-6

Cited by 61 publications

(26 citation statements)

References 29 publications

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“…First, organs and tumor overlap in many patients, and organs often contain tumor tissue, preventing exact uptake measurements (19)(20)(21). Furthermore, the organ sizes may vary substantially (20), and from 2D images it is not possible to estimate organ thicknesses or volumes.…”

Section: Discussionmentioning

confidence: 99%

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Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing ¹⁷⁷Lu-DOTA-Octreotate Treatment

et al. 2012

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The organs at risk in radionuclide therapy with 177 Lu-octreotate are the bone marrow and the kidneys. The primary aim of this study was to develop an individualized dosimetry protocol for the bone marrow. The secondary aim was to identify those patients, undergoing fractionated therapy with 7.4 GBq/cycle, who first reached an accumulated dose of either 2 Gy to the bone marrow or 23 Gy to the kidneys. Methods: Two hundred patients with metastatic neuroendocrine tumors with high somatostatin receptor expression were included. After the administration of 7.4 GBq of 177 Lu-octreotate, blood samples were drawn 6 times within the first 24 h. In 50 patients, additional blood samples were obtained at 96 and 168 h. Moreover, urine was collected from 30 patients during the first 24 h. Planar whole-body and SPECT/CT images over the abdomen were acquired at 24, 96, and 168 h after the infusion. Calculation of the absorbed radiation dose to the bone marrow was based on blood and urinary activity curves combined with organ-based analysis of the whole-body images. The absorbed dose to the kidney was calculated from the pharmacokinetic data obtained from SPECT/CT. Results: For a single cycle of 7.4 GBq, the absorbed dose to the bone marrow and the kidney ranged from 0.05 to 0.4 Gy and from 2 to 10 Gy, respectively. In 197 of 200 patients, the kidneys accumulated an absorbed dose of 23 Gy before the bone marrow reached 2 Gy. Between 2 and 10 cycles of 177 Lu-octreotate could be administered before the upper dose limit for the individual patient was reached. Conclusion: A method based on repeated whole-body imaging in combination with blood and urinary activity data over time was developed to determine the absorbed dose to the bone marrow. The dose-limiting organ was the kidney in 197 of 200 patients. In 50% of the patients, more than 4 cycles of 7.4 GBq of 177 Lu-octreotate could be administered, whereas 20% of the subjects were treated with fewer than 4 cycles. Individualized absorbed dose calculation is essential to optimize the therapy.

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Section: Discussionmentioning

confidence: 99%

“…Several studies have reported dosimetry data for the kidney based on 2-dimensional (2D) (1,8,16,18) or 3-dimensional (3D) (19)(20)(21)(22) imaging and attempted to tackle the question of the dose-limiting organ. In conventional external-beam radiotherapy, an absorbed dose limit of 23 Gy is used for the kidney (23).…”

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Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing ¹⁷⁷Lu-DOTA-Octreotate Treatment

et al. 2012

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“…Systemic radionuclide therapy with the lutetium-177 labeled somatostatin analogue [DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate) has shown promising therapeutic results for patients with neuroendocrine (NE) tumors for whom effective treatment is limited [1][2][3][4][5]. A pronounced tumor reduction is observed in many patients, but complete tumor remission is rare [2,5].…”

Section: Introductionmentioning

confidence: 99%

Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice

et al. 2011

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The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [(177)Lu-DOTA(0)-Tyr(3)]-octreotate and to investigate how the activity distribution influences the absorbed dose. Furthermore, the activity distribution of a second administration of radiolabeled octreotate was studied. Nude mice with subcutaneously grown human midgut carcinoid (GOT1) were injected intravenously with different amounts of (177)Lu-octreotate. At different time points thereafter (4 h to 13 days), a second injection of [(111)In-DOTA(0)-Tyr(3)]-octreotate was given to estimate the somatostatin receptor (sstr) expression. The activity distribution in the tumors was then determined. Monte Carlo simulations with PENELOPE were performed for dosimetry. Fifty-one out of 58 investigated tumors showed a lower activity concentration in the peripheral part than in the central part of the tumor. The amount of activity injected, or time after administration, did neither influence the relative activity nor the sstr distribution in the tumor. After an initial down-regulation (at 4-24 h), there was an up-regulation of sstr (1.5-2 times, at 7-14 days). Monte Carlo simulations demonstrated an inhomogeneous absorbed dose distribution in the tumor using (177)Lu, with twice as high absorbed dose centrally than peripherally. The high activity concentration centrally and the up-regulation of sstr demonstrated will facilitate fractionated therapy using radiolabeled somatostatin analogues if similar results will be obtained also in patients. The inhomogeneous activity distribution in the tumor has to be taken into account when the absorbed dose distribution in tumor is calculated.

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“…The limits for absorbed dose to the kidneys have been set at either 23 Gy (19,58) or 27 Gy (17,59). The use of the biologically effective dose allows for comparisons of therapies using a different number of cycles and other radionuclides such as 90 Y.…”

Section: Clinical Applications Of 177 Lumentioning

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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[¹⁷⁷Lu‐DOTA⁰‐Tyr³]‐Octreotate Treatment in Patients with Disseminated Gastroenteropancreatic Neuroendocrine Tumors: The Value of Measuring Absorbed Dose to the Kidney

Cited by 61 publications

References 29 publications

Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing ¹⁷⁷Lu-DOTA-Octreotate Treatment

Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing ¹⁷⁷Lu-DOTA-Octreotate Treatment

Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice

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

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[177Lu‐DOTA0‐Tyr3]‐Octreotate Treatment in Patients with Disseminated Gastroenteropancreatic Neuroendocrine Tumors: The Value of Measuring Absorbed Dose to the Kidney

Cited by 61 publications

References 29 publications

Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing 177Lu-DOTA-Octreotate Treatment

Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing 177Lu-DOTA-Octreotate Treatment

Inhomogeneous activity distribution of 177Lu-DOTA0-Tyr3-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice

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

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[¹⁷⁷Lu‐DOTA⁰‐Tyr³]‐Octreotate Treatment in Patients with Disseminated Gastroenteropancreatic Neuroendocrine Tumors: The Value of Measuring Absorbed Dose to the Kidney

Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing ¹⁷⁷Lu-DOTA-Octreotate Treatment

Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing ¹⁷⁷Lu-DOTA-Octreotate Treatment

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