Radretumab radioimmunotherapy in patients with brain metastasis: a 124I-L19SIP dosimetric PET study.
Radioimmunotherapy (RIT) with (131)I-labeled L19SIP (radretumab; a small immunoprotein format antibody directed against the ED-B domain of fibronectin; ∼ 80 kDa molecular weight) has been investigated in several clinical trials. Here, we describe the use of immuno-PET imaging with iodine-124 ((124)I)-labeled L19SIP to predict doses delivered to tumor lesions and healthy organs by a subsequent radretumab RIT in patients with brain metastases from solid cancer. Bone marrow doses were evaluated both during the diagnostic phase and posttherapy, measuring activities in blood (germanium detector) and whole body (lanthanum bromide detector). Expected doses for radretumab administration (4,107 MBq/m(2)) were calculated from data obtained after administration of an average of 167 MBq (124)I-L19SIP to 6 patients. To assess lesion average doses, the positron emission tomography (PET) scanner was calibrated for the use of (124)I with an International Electrotechnical Commission (IEC) Body Phantom and recovery coefficients were calculated. The average dose to bone red marrow was 0.21 Gy/GBq, with high correlation between provisional and actual posttherapy doses. Although the fraction of injected activity in normal organs was similar in different patients, the antibody uptake in the neoplastic lesions varied by as much as a factor of 60. Immuno-PET with (124)I-labeled L19SIP offers significant advantages over conventional (131)I imaging, in particular accuracy of dosimetric results. Furthermore, the study indicates that antibody uptake can be highly variable even in different lesions of the same patient and that immuno-PET procedures may guide product development with armed antibodies.
Authors' Affiliations: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Gian Luca
GL
Poli
Claudia
C
Bianchi
Giorgio
G
Virotta
Anna
A
Bettini
Renzo
R
Moretti
Eveline
E
Trachsel
Giuliano
G
Elia
Leonardo
L
Giovannoni
Dario
D
Neri
Andrea
A
Bruno
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
D000906:Antibodies; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C513931:SIP(L19) fusion protein