Adventures in radiosynthesis of clinical grade [68Ga]Ga-DOTA-Siglec-9.

Meeri Käkelä,Helena Virtanen,Sirpa Jalkanen,Heidi Liljenbäck,Juhani Knuuti,Pauliina Luoto,Tapio Viljanen,Xiang-Guo Li,Anne Roivainen

doi:10.1039/c7ra12423f

Abstract

We finally managed to establish a protocol for generating Good Manufacturing Practice (GMP)-grade gallium-68-labelled 1,4,7,0-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([68Ga]Ga-DOTA-Siglec-9), the first radiopharmaceutical for positron emission tomography imaging of vascular adhesion protein 1.

Highlights

Vascular adhesion protein 1 (VAP-1) is prominently involved in immune cell trafficking in a number of major human diseases, including rheumatoid arthritis, certain cancers, and atherosclerosis.[1]
VAP-1 has the unique characteristic of rapidly relocating from intracellular granules onto luminal cell surfaces upon in ammation, making it an ideal target for imaging of in ammation.1a,3 a few peptide-based ligands and radiolabelled antibodies have been developed in Turku for imaging of VAP-1 using positron emission tomography (PET) techniques.[3,4]
We have performed extensive PET studies using Siglec-9 as a lead VAP-1 targeting compound and have modi ed the peptide with 8-amino-3,6-dioxaoctanoyl spacer, amidation, acylation, glycosylation, or labelled it with various radionuclides.1a,3 Among the gallium-68 (68Ga)-labelled variants, [68Ga]Ga-DOTA-Siglec-9 (Scheme 1, DOTA denotes 1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid) has been most promising in our preclinical evaluations. [68Ga]Ga-DOTA-Siglec-9 enables clear target visualization in a number of disease models in mice, rats, rabbits, and pigs, including synovitis, sterile skin in ammation, atherosclerosis, and acute respiratory distress syndrome.1a,3a,5 [68Ga]Ga-DOTA-Siglec-9 is useful for PET imaging of in ammation in infection models, representing a novel direction for its application.[6]

Summary

Introduction

Vascular adhesion protein 1 (VAP-1) is prominently involved in immune cell trafficking in a number of major human diseases, including rheumatoid arthritis, certain cancers, and atherosclerosis.[1]. The reaction vessel was preloaded with a mixture of sodium acetate buffer, absolute ethanol or ascorbic acid, and precursor DOTA-Siglec-9 (80 mL, 40 mg, 16.5 nmol). We added different amounts (60– 120 mg mLÀ1) of non-radiolabelled GMP-grade precursor compound DOTA-Siglec-9 to the HPLC samples of our [68Ga]-labelled end product.

Results

Conclusion