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Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
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2013 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 1, 33-41 p.Article in journal (Refereed) Published
Abstract [en]

The organs at risk in radionuclide therapy with 177Lu-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 177Lu-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 177Lu-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 177Lu-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.

Place, publisher, year, edition, pages
2013. Vol. 54, no 1, 33-41 p.
Keyword [en]
177Lu-DOTA-octreotate, Bone marrow, Dosimetry, Individualized, Kidney
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-183412DOI: 10.2967/jnumed.112.107524ISI: 000313606800027OAI: oai:DiVA.org:uu-183412DiVA: diva2:562728
Available from: 2012-10-25 Created: 2012-10-25 Last updated: 2017-12-07Bibliographically approved
In thesis
1. 177Lu-DOTA-octreotate Radionuclide Therapy of Neuroendocrine Tumours: Dosimetry-Based Therapy Planning and Outcome
Open this publication in new window or tab >>177Lu-DOTA-octreotate Radionuclide Therapy of Neuroendocrine Tumours: Dosimetry-Based Therapy Planning and Outcome
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Peptide receptor radionuclide therapy for the internal radiation of neuroendocrine tumours expressing somatostatin receptors has made great advances and offers promising results. 177Lu-DOTA-octreotate is one of the most widely used radiopeptides, but kidneys and bone marrow are organs at risk. Methods of measuring radiation doses to at-risk organs and tumours (dosimetry) on an individual patient basis have been regarded as impracticable and a maximum of 4 treatment cycles has widely been accepted as the treatment standard instead.

The first aim of this thesis was to establish a clinically feasible protocol to calculate absorbed doses to bone marrow and the kidneys during therapy with 177Lu-DOTA-octreotate. A new dosimetry protocol for the bone marrow was described. Dosimetry for solid organs had previously been described based on 3-dimensional imaging by the research group. In the current thesis it was demonstrated that in most patients only minor changes of the effective half-life occurred in the kidneys. By performing complete dosimetry during the first cycle and comparing it with the uptake in later cycles, it was shown that the absorbed dose can be cal-culated based on the activity concentration at 24 hours after therapy. The study concluded that 50% of all patients could receive more than the standard 4 treatment cycles with 7.4 GBq 177Lu-DOTA-octreotate without passing the limit of 23 Gray to the kidneys or 2 Gray to the bone marrow, whereas 20% would tolerate fewer than 4 cycles. 

The second aim was to describe treatment outcomes of dosimetry-guided therapy with 177Lu-DOTA-octreotate. Patients with metastasized colorectal neuroendocrine tumours and bronchial carcinoids were shown to have longer survival with this method than previously reported. Morphological tumour response could be correlated to time to progression. Furthermore, in a case of low-differentiated neuroendocrine cancer it was shown that large tumours with high proliferation can also be treated with this method and that tumour-to-risk organ ratios can improve in later cycles, resulting in a more effective treatment.

Dosimetry-guided, fractionated radionuclide therapy with 177Lu-DOTA-octreotate is a valuable treatment option for patients with advanced neuroendocrine tumours expressing somatostatin receptors.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 831
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-183417 (URN)978-91-554-8513-9 (ISBN)
Public defence
2012-12-08, Grönwallsalen, Akademiska Sjukhuset Ing. 70, Uppsala, 09:15 (English)
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Available from: 2012-11-16 Created: 2012-10-25 Last updated: 2013-01-23Bibliographically approved

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Garske-Román, UlrikeGranberg, DanJohansson, SilviaEriksson, BarbroSundin, AndersLundqvist, HansLubberink, Mark

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