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Dosimetry of Radionuclide Therapy with 177Lu-octreotate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In radionuclide therapy it is still common to administer standard activities or to scale administered activity with blunt parameters such as body weight or surface area. This is not ideal because, due to considerable variation in kinetics, large safety margins have to be applied to avoid radiation damage to healthy organs, which causes under-treatment of many patients. To base the administered activity on individual dosimetry, as in other therapy modalities using ionizing radiation, will essentially solve this problem. However, dosimetry in radionuclide therapy is resource-demanding and debilitating for the patient because it involves a number of measurements to determine the kinetics of the therapy radionuclide and needs to be optimized for clinical feasibility.

First, the ability to measure radioactivity distributions of radionuclides for therapy was investigated. SPECT measurements of 177Lu, which was later used clinically, showed good spatial resolution and a reasonable quantitative accuracy.

A new method to calculate absorbed dose to solid risk organs and tumours was developed and applied in the clinic. Kinetic data were obtained by repeated SPECT measurements. Radiation concentration determined in small volumes of interest could then be multiplied by a constant to obtain absorbed dose because it was shown that cross-fire was negligible in organs with high activity concentration. The new dosimetry method, compared to other methods, was found to give better results with less effort. In addition, a method to calculate absorbed dose to bone marrow was developed and clinically implemented.

In 200 patients, individual kinetics and absorbed dose were studied and variations were found to be large. Kidney was the dose-limiting organ in almost all patients (98.5%). Keeping the kidney dose < 23Gy, about half of the patients could receive 5, or up to 10 treatments instead of the stipulated 4.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 58 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 707
Keyword [en]
177Lu-octreotate, Absorbed dose, Neuroendocrine tumour
National Category
Cancer and Oncology
Research subject
Medical Radiophysics
Identifiers
URN: urn:nbn:se:uu:diva-158973ISBN: 978-91-554-8171-1 (print)OAI: oai:DiVA.org:uu-158973DiVA: diva2:443143
Public defence
2011-11-15, Grönwallsalen, Akademiska sjukhuset Ing. 70, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-10-24 Created: 2011-09-19 Last updated: 2011-11-04Bibliographically approved
List of papers
1. Performance of coincidence imaging with long-lived positron emitters as an alternative to dedicated PET and SPECT
Open this publication in new window or tab >>Performance of coincidence imaging with long-lived positron emitters as an alternative to dedicated PET and SPECT
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2004 (English)In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 49, no 24, 5419-32 p.Article in journal (Refereed) Published
Abstract [en]

An important application of quantitative imaging in nuclear medicine is the estimation of absorbed doses in radionuclide therapy. Depending on the radionuclide used for therapy, quantitative imaging of the kinetics of the therapeutic radiopharmaceutical could be done using planar imaging, SPECT or PET. Since many nuclear medicine departments have a gamma camera system that is also suitable for coincidence imaging, the performance of these systems with respect to quantitative imaging of PET isotopes that could be of use in radionuclide dosimetry is of interest. We investigated the performance of a gamma camera with coincidence imaging capabilities with 99mTc, 111In, 18F and 76Br and a dedicated PET system with 18F and 76Br, using a single standard set of phantom measurements. Here, 76Br was taken as a typical example of prompt gamma-emitting PET isotopes that are applicable in radionuclide therapy dosimetry such as 86Y and 124I. Image quality measurements show comparable image contrasts for 76Br coincidence imaging and 111In SPECT. Although the spatial resolution of coincidence imaging is better than single photon imaging, the contrast obtained with 76Br is not better than that with 99mTc or 111In because of the prompt gamma involved. Additional improvements are necessary to allow for quantitative coincidence imaging of long-lived, prompt gamma producing positron emitters.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-72947 (URN)10.1088/0031-9155/49/24/002 (DOI)15724533 (PubMedID)
Available from: 2005-09-26 Created: 2005-09-26 Last updated: 2017-12-14Bibliographically approved
2. Individualized dosimetry in patients undergoing therapy with Lu-177-DOTA-D-Phe(1)-Tyr(3)-octreotate
Open this publication in new window or tab >>Individualized dosimetry in patients undergoing therapy with Lu-177-DOTA-D-Phe(1)-Tyr(3)-octreotate
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2010 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, no 2, 212-225 p.Article in journal (Refereed) Published
Abstract [en]

In recent years, targeted radionuclide therapy with [Lu-177-DOTA(0), Tyr(3)]octreotate for neuroendocrine tumours has yielded promising results. This therapy may be further improved by using individualized dosimetry allowing optimization of the absorbed dose to the tumours and the normal organs. The aim of this study was to investigate the feasibility and reliability of individualized dosimetry based on SPECT in comparison to conventional planar imaging. Attenuation-corrected SPECT data were analysed both by using organ-based volumes of interest (VOIs) to obtain the total radioactivity in the organ, and by using small VOIs to measure the tissue radioactivity concentration. During the first treatment session in 24 patients, imaging was performed 1, 24, 96 and 168 h after [Lu-177-DOTA(0), Tyr(3)]octreotate infusion. Absorbed doses in non tumour-affected kidney, liver and spleen were calculated and compared for all three methods (planar imaging, SPECT organ VOIs, SPECT small VOIs). Planar and SPECT dosimetry were comparable in areas free of tumours, but due to overlap the planar dosimetry highly overestimated the absorbed dose in organs with tumours. Furthermore, SPECT dosimetry based on small VOIs proved to be more reliable than whole-organ dosimetry. We conclude that SPECT dosimetry based on small VOIs is feasible and more accurate than conventional planar dosimetry, and thus may contribute towards optimising targeted radionuclide therapy.

Keyword
Neuroendocrine tumours, Individualized dosimetry, Targeted radionuclide therapy, [Lu-177-DOTA(0), Tyr(3)]Octreotate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-138035 (URN)10.1007/s00259-009-1216-8 (DOI)000274293900003 ()19727718 (PubMedID)
Available from: 2010-12-16 Created: 2010-12-16 Last updated: 2017-12-11Bibliographically approved
3. Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy
Open this publication in new window or tab >>Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy
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2011 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 1, 86-96 p.Article in journal (Refereed) Published
Abstract [en]

Fractionated (177)Lu-DOTA-octreotate therapy has been reported to be an effective treatment option for patients with generalized neuroendocrine tumors. In our clinic, full individual dosimetry is performed during the first therapy cycle, while dosimetry at later cycles is based on the 24 h uptake measurement assuming an unchanged effective half-life. Our aim was to evaluate this assumption and the variation in the 24 h uptake during therapy. Patients. Thirty patients, 13 women and 17 men, were included in the study. Methods. During the first therapy cycle the (177)Lu-concentration was measured with SPECT/CT over the abdomen at 24 h, 96 h and 168 h after infusion. The effective half-life was determined for the kidneys, liver and spleen. The procedure was repeated at cycle 4 or 5. Results. The median ratio between the effective half-lives of the latter and the first cycle was 0.97 and 1.01 for the right and left kidney, with a range of 0.89-1.01 (1st-3rd quartile) and 0.93-1.05, respectively. Discussion. The mean value of the ratios was slightly lower than one, indicating a tendency towards increased activity elimination during therapy. In individual patients, significant changes were found for all organs, often when a large tumor burden reduction occurred during treatment. Possible contributing factors appeared to be larger amounts of non-tumor bound tracer, improved organ function (kidneys), decrease of vessel obstruction (spleen), less scatter from large tumors and reduction of small metastases (liver and spleen). Conclusion. With most patients it is safe to estimate absorbed doses to kidneys, liver and spleen from 24 h activity concentration assuming an unchanged effective half-life during therapy. Patients with risk factors for kidney dysfunction need to be monitored in more detail. Simplified dosimetry based on the assumption of unchanged effective half-life can function as guidance to the number of therapy cycles an individual patient can tolerate.

Keyword
Absorbed dose, Neuroendocrine tumour, 177Lu-octreotate
National Category
Cancer and Oncology
Research subject
Physics; Oncology; Radiology
Identifiers
urn:nbn:se:uu:diva-158969 (URN)10.3109/0284186X.2011.618511 (DOI)000298002000012 ()21961497 (PubMedID)
Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2017-12-08Bibliographically approved
4. Absorbed doses to kidney and bone marrow in 200 patients undergoing therapy with 177Lu-DOTA-D-Phe1-Tyr3-octreotate
Open this publication in new window or tab >>Absorbed doses to kidney and bone marrow in 200 patients undergoing therapy with 177Lu-DOTA-D-Phe1-Tyr3-octreotate
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(English)Manuscript (preprint) (Other academic)
Keyword
177Lu-octreotate, Absorbed dose, Neuroendocrine tumour
National Category
Cancer and Oncology
Research subject
Physics; Oncology; Radiology
Identifiers
urn:nbn:se:uu:diva-158971 (URN)
Available from: 2011-09-19 Created: 2011-09-19 Last updated: 2011-11-04

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