Radiolabelling DOTA-peptides with 68Ga.
OBJECTIVE
A new field of interest is the application of 68Ga-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO2-based commercially available 68Ge/68Ga generator.


METHODS
Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter 68Ga, finger dosimetric measurements were performed during radiolabelling and in vivo administration.


RESULTS
Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 nM; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5-4. Plastic shielding (> or =7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats 68GaCl3 had slow clearance from blood, while 68Ga-EDTA was rapidly cleared via the kidneys. Uptake of 68Ga-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection.


CONCLUSIONS
DOTA-peptides for PET imaging can be labelled with 68Ga up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.
Breeman
Wouter A P
WA
Department of Nuclear Medicine, University Medical Center Rotterdam, Erasmus MC Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. w.a.p.breeman@erasmusmc.nl
de Jong
Marion
M
de Blois
Erik
E
Bernard
Bert F
BF
Konijnenberg
Mark
M
Krenning
Eric P
EP
D000818:Animals; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D015282:Octreotide / Q000031:analogs & derivatives; D009928:Organ Specificity; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
C476041:DOTA-Tyr(1)-octreotate; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D015282:Octreotide