Tumour targeting and radiation dose of radioimmunotherapy with 90Y-rituximab in CD20+ B-cell lymphoma as predicted by 89Zr-rituximab immuno-PET: impact of ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03-20

AUTHORS

Kristoff Muylle, Patrick Flamen, Danielle J. Vugts, Thomas Guiot, Ghanem Ghanem, Nathalie Meuleman, Pierre Bourgeois, Bruno Vanderlinden, Guus A. M. S. van Dongen, Hendrik Everaert, Mélanie Vaes, Dominique Bron

ABSTRACT

PurposeTo compare using immuno-PET/CT the distribution of 89Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with 90Y-labelled rituximab in CD20+ B-cell lymphoma.MethodsFive patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline 89Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m2) of unlabelled rituximab followed by injection of 89Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by 90Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed.ResultsWith a cold rituximab preload, the calculated whole-body dose of 90Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82–0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion.ConclusionAdministration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the “prerituximab era”.Clinical Trial Application: CTA 2011-005474-38Trial Registry: EudraCT More... »

PAGES

1304-1314

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00259-015-3025-6

DOI

http://dx.doi.org/10.1007/s00259-015-3025-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022862677

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25792453


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26 schema:description PurposeTo compare using immuno-PET/CT the distribution of 89Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with 90Y-labelled rituximab in CD20+ B-cell lymphoma.MethodsFive patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline 89Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m2) of unlabelled rituximab followed by injection of 89Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by 90Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed.ResultsWith a cold rituximab preload, the calculated whole-body dose of 90Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82–0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion.ConclusionAdministration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the “prerituximab era”.Clinical Trial Application: CTA 2011-005474-38Trial Registry: EudraCT
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33 schema:keywords B cells
34 B-cell depletion
35 B-cell lymphoma
36 CD20
37 CT
38 CT imaging
39 ConclusionAdministration
40 MethodsFive patients
41 PET/CT
42 PET/CT imaging
43 PurposeTo
44 ResultsWith
45 administration
46 cells
47 changes
48 common practice
49 depletion
50 disease
51 distribution
52 dose
53 era
54 high dose
55 high preload
56 high tumor uptake
57 imaging
58 immuno-PET
59 impact
60 impairs
61 increase
62 injection
63 lesions
64 lymphoma
65 majority
66 majority of patients
67 organs
68 origin
69 patients
70 phase
71 phase 1
72 practice
73 preload
74 prerituximab era
75 progressive disease
76 radiation dose
77 radioimmunotherapy
78 rationale
79 regimens
80 registry
81 rituximab
82 significant changes
83 spleen
84 study phase
85 targeting
86 therapeutic regimens
87 tracer uptake
88 tumor targeting
89 tumor uptake
90 tumors
91 uptake
92 weeks
93 whole-body dose
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