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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-08-2009 | Original Article

¹²⁴I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of ¹³¹I-L19-SIP radioimmunotherapy

Authors: Bernard M. Tijink, Lars R. Perk, Marianne Budde, Marijke Stigter-van Walsum, Gerard W. M. Visser, Reina W. Kloet, Ludger M. Dinkelborg, C. René Leemans, Dario Neri, Guus A. M. S. van Dongen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2009

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 ¹³¹I-L19-SIP was recently started. In the present study, after GMP production of ¹²⁴I and efficient production of ¹²⁴I-L19-SIP, we aimed to demonstrate the suitability of ¹²⁴I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical ¹³¹I-L19-SIP RIT.

Methods

¹²⁴I was produced in a GMP compliant way via ¹²⁴Te(p,n)¹²⁴I 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 ¹²⁴I- and ¹³¹I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while ¹²⁴I PET images were obtained from mice with tumours of <50 to ∼700 mm³.

Results

¹²⁴I 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 ¹²⁴I-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 biodistribution results were obtained with ¹²⁴I- and ¹³¹I-L19-SIP. Immuno-PET with ¹²⁴I-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

¹²⁴I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with ¹²⁴I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting ¹³¹I-L19-SIP biodistribution.

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Title: 124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy
Authors: Bernard M. Tijink
Lars R. Perk
Marianne Budde
Marijke Stigter-van Walsum
Gerard W. M. Visser
Reina W. Kloet
Ludger M. Dinkelborg
C. René Leemans
Dario Neri
Guus A. M. S. van Dongen
Publication date: 01-08-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1096-y

At a glance: The STEP trials

Springer Medicine

¹²⁴I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of ¹³¹I-L19-SIP radioimmunotherapy

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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