Buck, Andreas

Herrmann, Ken

Hoffmann, F.

Lapa, Constantin

Lassmann, Michael

Osl, Theresa

Poschenrieder, Andreas

Schottelius, Margret

Schwaiger, Markus

Wester, Hans

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[177]Lu-pentixather: preclinical and first patient results with a highly promising CXCR4-directed endoradiotherapeutic agent

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                                                              [ ]Lu-pentixather: preclinical and first patient results with ahighly promising CXCR4-directed endoradiotherapeutic agentMargret Schottelius, Theresa Osl, Andreas Poschenrieder, Ken Herrmann, Constantin Lapa, F. Hoffmann, Markus Schwaiger, Michael Lassmann,Andreas Buck and Hans Wester                                                            177                             Abstract339Objectives Recent patient studies revealed superb CXCR4 targeting characteristics of [ Ga]pentixafor for in vivo PET-quantification of CXCR4 expression.To exploit this innovative targeting concept for CXCR4-directed PRRT, [ Lu]pentixather, a structural analog of [ Ga]pentixafor, was developed andevaluated.Methods CXCR4-affinities and receptor selectivities were determined using Jurkat and transiently transfected CHO-K1 cells. CXCR4-specific uptake of[ Lu]pentixather was studied in various human cancer cell lines. Biodistribution was carried out in Daudi lymphoma bearing SCID mice. After pretherapeuticdosimetry (238 MBq), a first MM patient received 15.2 GBq [ Lu]pentixather. Tracer kinetics 1-15d p.i. were assessed via SPECT/CT and planarscintigraphy. Therapy response was monitored via [ F]FDG-PET/CT.Results [ Lu]pentixather binds to human CXCR4 with unchanged excellent affinity and selectivity. Its uptake in human cancer cells closely reflects theCXCR4 expression determined by FACS. In Daudi xenografts, [ Lu]pentixather shows high CXCR4-specific accumulation and persistent retention (6.8±0.7,3.3±0.4, 2.1±0.1 and 2.1±0.4 %iD/g at 6, 48 and 96h and 8d p.i.). In the MM patient, high uptake and long retention (>15d) of [ Lu]pentixather in lesions leadto tumor doses of 10-58 Gy. Doses to kidney, liver and bone marrow were 8.5, 5.5 and 1.8 Gy. [ F]FDG-PET/CT at 21d p.i. revealed partly complete, partlypartial metabolic response.Conclusions [ Lu]pentixather shows outstanding CXCR4-targeting properties both in vitro and in vivo. Adequate clearance kinetics and tumor retentionlead to the deposition of high therapeutic doses in tumors with low doses to non-target tissues. The promising therapy response achieved with[ Lu]pentixather-PRRT warrants the further evaluation of pentixather labeled with therapeutic radioisotopes in a larger cohort of patients.           68177 681771771817717717718177177                                                                                                                                                                                 

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[177]Lu-pentixather: preclinical and first patient results with a highly promising CXCR4-directed endoradiotherapeutic agent [Abstract]

[177]Lu-pentixather: preclinical and first patient results with a highly promising CXCR4-directed endoradiotherapeutic agent

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