Synthesis, Characterisation and Application of 68Ga-labelled Macromolecules

The positron emitting radionuclide 68Ga (T1/2 = 68 min) might become of practical interest for clinical positron emission tomography (PET). The metallic cation, 68Ga(III), is suitable for complexation with chelators, either naked or conjugated with biological macromolecules. Such labelling procedures require pure and concentrated preparations of 68Ga(III), which cannot be sufficiently fulfilled by the presently available 68Ge/68Ga generator eluate. This thesis presents methods to increase the concentration and purity of 68Ga obtained from a commercial 68Ge/68Ga generator. The use of the preconcentrated and purified 68Ga eluate along with microwave heating allowed quantitative 68Ga-labelling of peptide conjugates within 15 min. The specific radioactivity of the radiolabelled peptides was improved considerably compared to previously applied techniques using non-treated generator eluate and conventional heating. A commercial 68Ge/68Ga generator in combination with the method for preconcentration/purification and microwave heated labelling might result in an automated device for 68Ga-based radiopharmaceutical kit production with quantitative incorporation of 68Ga(III).Macromolecules were labelled with 68Ga(III) either directly or via a chelator. The bifunctional chelator, DOTA, was conjugated in solution to peptides, an antibody and oligonucleotides. The peptides had varied pI values, constitution, and length ranging from 8 to 53 amino acid residues. The oligonucleotides were of various sequences and length with modifications in backbone, sugar moiety and both 3′ and 5′ ends with a molecular weight up to 9.8 kDa…


1.1 Aims of the study
2.1 Imaging techniques: Positron Emission Tomography
2.2 The generator produced
Ga radiometal
2.3 Radiometallation
2.3.1 Microwave heating in radiolabelling chemistry
2.4 Macromolecular tracers
2.4.1 Peptides/proteins/antibodies
2.4.2 Oligonucleotides
2.5 Specific radioactivity
2.6 68 Ga-labelled peptides as a tool to study analytical devices
3.1 The preparation of 68Ga(III)
3.1.1 68Ge/68 Ga generator characterisation
3.1.2 Preconcentration/purification of 68Ge/68 Ga generator eluate
3.2 Conjugation of DOTA with macromolecules
3.3 Chelator mediated Ga-labelling of the bioconjugates
3.3.1 The influence of microwave heating
3.4 Specific radioactivity
3.5 68
Ga-labelling of DOTA-Trastuzumab
3.6 Direct complexation of 68 Ga with Lactoferrin
3.7 Characterisation of the macromolecular conjugates and their 68 Ga-labelled counterparts
3.7.1 Chemical characterisation
3.7.2 Preliminary chemical and biological examination of the 68
Ga-labelled oligonucleotide conjugates
3.7.3 Biological characterisation of the 68
Ga-labelled peptide conjugates
3.8 68 Ga-labelled peptides for adsorption studies

Author: Velikyan, Irina

Source: Uppsala University Library

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