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Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET. (Nuklearmedicin)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Avdelningen för sjukhusfysik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
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2011 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, nr 1, s. 86-96Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2011. Vol. 51, nr 1, s. 86-96
Nyckelord [en]
Absorbed dose, Neuroendocrine tumour, 177Lu-octreotate
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
Fysik; Onkologi; Radiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-158969DOI: 10.3109/0284186X.2011.618511ISI: 000298002000012PubMedID: 21961497OAI: oai:DiVA.org:uu-158969DiVA, id: diva2:441914
Tillgänglig från: 2011-09-19 Skapad: 2011-09-19 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
Ingår i avhandling
1. Dosimetry of Radionuclide Therapy with 177Lu-octreotate
Öppna denna publikation i ny flik eller fönster >>Dosimetry of Radionuclide Therapy with 177Lu-octreotate
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2011. s. 58
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 707
Nyckelord
177Lu-octreotate, Absorbed dose, Neuroendocrine tumour
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
Medicinsk radiofysik
Identifikatorer
urn:nbn:se:uu:diva-158973 (URN)978-91-554-8171-1 (ISBN)
Disputation
2011-11-15, Grönwallsalen, Akademiska sjukhuset Ing. 70, Uppsala, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2011-10-24 Skapad: 2011-09-19 Senast uppdaterad: 2011-11-04Bibliografiskt granskad
2. 177Lu-DOTA-octreotate Radionuclide Therapy of Neuroendocrine Tumours: Dosimetry-Based Therapy Planning and Outcome
Öppna denna publikation i ny flik eller fönster >>177Lu-DOTA-octreotate Radionuclide Therapy of Neuroendocrine Tumours: Dosimetry-Based Therapy Planning and Outcome
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2012. s. 59
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 831
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-183417 (URN)978-91-554-8513-9 (ISBN)
Disputation
2012-12-08, Grönwallsalen, Akademiska Sjukhuset Ing. 70, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2012-11-16 Skapad: 2012-10-25 Senast uppdaterad: 2013-01-23Bibliografiskt granskad

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Garske, UlrikeSandström, MattiasJohansson, SilviaSundin, AndersGranberg, DanEriksson, BarbroLundqvist, Hans

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