Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate
Identifieur interne : 001060 ( Main/Merge ); précédent : 001059; suivant : 001061Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate
Auteurs : Flavio Forrer [Pays-Bas] ; Eric P. Krenning [Pays-Bas] ; Peter P. Kooij [Pays-Bas] ; Bert F. Bernard [Pays-Bas] ; Mark Konijnenberg [Pays-Bas] ; Willem H. Bakker [Pays-Bas] ; Jaap J. M. Teunissen [Pays-Bas] ; Marion De Jong [Pays-Bas] ; Kirsten Van Lom [Pays-Bas] ; Wouter W. De Herder [Pays-Bas] ; Dik J. Kwekkeboom [Pays-Bas]Source :
- European Journal of Nuclear Medicine and Molecular Imaging [ 1619-7070 ] ; 2009.
Abstract
Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called “remainder of the body” to the bone marrow.
Bone marrow aspirates were drawn in 15 patients after treatment with [177Lu-DOTA0,Tyr3]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment.
A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (
(1) After PRRT with [177Lu-DOTA0,Tyr3]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow absorbed dose is necessary.
Url:
DOI: 10.1007/s00259-009-1072-6
PubMed: 19247653
PubMed Central: 2691529
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Lu-DOTA<sup>0</sup>
,Tyr<sup>3</sup>
]octreotate</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Bone marrow dosimetry in peptide receptor radionuclide therapy with [<sup>177</sup>
Lu-DOTA<sup>0</sup>
,Tyr<sup>3</sup>
]octreotate</title>
<author><name sortKey="Forrer, Flavio" sort="Forrer, Flavio" uniqKey="Forrer F" first="Flavio" last="Forrer">Flavio Forrer</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
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</affiliation>
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<author><name sortKey="Krenning, Eric P" sort="Krenning, Eric P" uniqKey="Krenning E" first="Eric P." last="Krenning">Eric P. Krenning</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
<wicri:noRegion>NL-3015 GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kooij, Peter P" sort="Kooij, Peter P" uniqKey="Kooij P" first="Peter P." last="Kooij">Peter P. Kooij</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Bernard, Bert F" sort="Bernard, Bert F" uniqKey="Bernard B" first="Bert F." last="Bernard">Bert F. Bernard</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
<wicri:noRegion>NL-3015 GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Konijnenberg, Mark" sort="Konijnenberg, Mark" uniqKey="Konijnenberg M" first="Mark" last="Konijnenberg">Mark Konijnenberg</name>
<affiliation wicri:level="1"><nlm:aff id="Aff2">Research and Development, Mallinckrodt Medical BV, Covidien, Petten, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Research and Development, Mallinckrodt Medical BV, Covidien, Petten</wicri:regionArea>
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<author><name sortKey="Bakker, Willem H" sort="Bakker, Willem H" uniqKey="Bakker W" first="Willem H." last="Bakker">Willem H. Bakker</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
<wicri:noRegion>NL-3015 GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Teunissen, Jaap J M" sort="Teunissen, Jaap J M" uniqKey="Teunissen J" first="Jaap J. M." last="Teunissen">Jaap J. M. Teunissen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
<wicri:noRegion>NL-3015 GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="De Jong, Marion" sort="De Jong, Marion" uniqKey="De Jong M" first="Marion" last="De Jong">Marion De Jong</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
<wicri:noRegion>NL-3015 GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Lom, Kirsten" sort="Van Lom, Kirsten" uniqKey="Van Lom K" first="Kirsten" last="Van Lom">Kirsten Van Lom</name>
<affiliation wicri:level="3"><nlm:aff id="Aff3">Department of Haematology, Erasmus MC Rotterdam, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Haematology, Erasmus MC Rotterdam, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Herder, Wouter W" sort="De Herder, Wouter W" uniqKey="De Herder W" first="Wouter W." last="De Herder">Wouter W. De Herder</name>
<affiliation wicri:level="3"><nlm:aff id="Aff4">Department of Internal Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus MC Rotterdam, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kwekkeboom, Dik J" sort="Kwekkeboom, Dik J" uniqKey="Kwekkeboom D" first="Dik J." last="Kwekkeboom">Dik J. Kwekkeboom</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Nuclear Medicine, Erasmus MC Rotterdam, Dr. Molewaterplein 40, NL-3015 GD Rotterdam</wicri:regionArea>
<wicri:noRegion>NL-3015 GD Rotterdam</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">European Journal of Nuclear Medicine and Molecular Imaging</title>
<idno type="ISSN">1619-7070</idno>
<idno type="eISSN">1619-7089</idno>
<imprint><date when="2009">2009</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Purpose</title>
<p>Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called “remainder of the body” to the bone marrow.</p>
</sec>
<sec><title>Methods</title>
<p>Bone marrow aspirates were drawn in 15 patients after treatment with [<sup>177</sup>
Lu-DOTA<sup>0</sup>
,Tyr<sup>3</sup>
]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment.</p>
</sec>
<sec><title>Results</title>
<p>A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (<italic>r</italic>
=0.914, <italic>p</italic>
<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose.</p>
</sec>
<sec><title>Conclusion</title>
<p>(1) After PRRT with [<sup>177</sup>
Lu-DOTA<sup>0</sup>
,Tyr<sup>3</sup>
]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow absorbed dose is necessary.</p>
</sec>
</div>
</front>
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