(124)I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of (131)I-L19-SIP radioimmunotherapy
Abstract
Purpose: The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131 I-L19-SIP was recently started. In the present study, after GMP production of 124 I and efficient production of 124 I-L19-SIP, we aimed to demonstrate the suitability of 124 I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical 131 I-L19-SIP RIT. Methods: 124 I was produced in a GMP compliant way via 124 Te(p,n) 124 I reaction and using a TERIMO™ module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected 124 I- and 131 I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while 124 I PET images were obtained from mice with tumours of <50 to ∼700 mm 3 . Results: 124 I was produced highly pure with an average yield of 15.4±0.5 MBq/μAh, while separation yield was ∼90% efficient with <0.5% loss of TeO2. Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for 124 I-L19-SIP: ∼80 , 99.9 and >90%, respectively. Tumour uptake was 7.3±2.1, 10.8±1.5, 7.8±1.4, 5.3±0.6 and 3.1±0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribu- tion results were obtained with 124 I- and 131 I-L19-SIP. Immuno-PET with 124 I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm3 and no adverse uptake in other organs. Conclusions: 124 I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with 124 I-L19-SIP appeared qualified for sensitive imaging of tumour neo- vasculature and for predicting 131 I-L19-SIP biodistribution. Show more
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https://doi.org/10.3929/ethz-b-000021910Publication status
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Journal / series
European Journal of Nuclear Medicine and Molecular ImagingVolume
Pages / Article No.
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SpringerSubject
PET imaging; L19-SIP; Extra domain B of fibronectin; Angiogenesis; RadioimmunotherapyMore
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