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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2007

01-01-2007 | Original article

Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT®)

Authors: Nicoletta Urbano, Stefano Papi, Mauro Ginanneschi, Rita De Santis, Silvia Pace, Ragnar Lindstedt, Liliana Ferrari, SunJu Choi, Giovanni Paganelli, Marco Chinol

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2007

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Abstract

Purpose

A novel biotin-DOTA conjugate (r-BHD: reduced biotinamidohexylamine-DOTA) was investigated in order to provide an efficient pretargeted antibody-guided radioimmunotherapy (PAGRIT®) application. Preclinical and clinical results are described.

Methods

90Y and 177Lu were used to label r-BHD. The effect of pH and a wide range of specific activities were studied. Radiolabelled r-BHD was tested for affinity towards avidin and for stability in saline or in human serum with and without ascorbic acid. Pharmacokinetic data were collected and organ biodistribution evaluated in a tumour-bearing pretargeted animal model. A pilot study was performed in a metastatic melanoma patient and dosimetry was estimated.

Results

High radiochemical purity (>99%) was routinely achieved with 90Y or 177Lu in sodium acetate buffer (1.0 M, pH 5.0) at a specific activity of 2.6 MBq/nmol. Both 90Y- and 177Lu-r-BHD were also prepared at higher specific activities. Radiolabelled r-BHD was stable up to 96 h in human serum and saline with the addition of ascorbic acid. The structural modifications proposed for the r-BHD stabilised it against enzymatic degradation while retaining high binding affinity for avidin. Renal clearance appeared to be the main route of excretion in animals, and high tumour uptake was observed in the pretargeted animals. The patient study showed a total body clearance of ∼85% in 24 h, with a kidney absorbed dose of 1.5 mGy/MBq. Tumour uptake was rapid and the calculated dose to a 10-mm tumour lesion was ∼12 mGy/MBq.

Conclusion

These results indicate that the new biotin-DOTA conjugate may be a suitable candidate for pretargeting trials.
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Metadata
Title
Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT®)
Authors
Nicoletta Urbano
Stefano Papi
Mauro Ginanneschi
Rita De Santis
Silvia Pace
Ragnar Lindstedt
Liliana Ferrari
SunJu Choi
Giovanni Paganelli
Marco Chinol
Publication date
01-01-2007
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-006-0124-4

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