68Ge/68Ga Generators and 68Ga Radiopharmaceutical Chemistry on Their Way into a New Century

Abstract

68Ga faces a renaissance initiated by the development of new 68Ge/68Ga radionuclide generators, sophisticated 68Ga radiopharmaceuticals, preclinical research and state-of-the-art clincial diagnoses via positron emission tomography/computed tomography (PET/CT). A new type of 68Ge/68Ga generator became commercially available in the first years of the 21st century, with eluates based on hydrochloric acid. These generators provided ‘cationic’ 68Ga instead of ‘inert’ 68Gacomplexes, and opened new pathways of MeIII radiopharmaceutical chemistry. The last decade has seen a 68Ga rush. Increasing interest in generator-based 68Ga radiopharmaceuticals in diagnostic applications has been accompanied by its potential use in the context of diease treatment planning, made possible by the inherent option expressed by theranostics. However, widespread acceptance and clinical application requires optimization of 68Ge/68Ga generators both from chemical and regulatory perspectives. How to cite this article Rösch F. 68Ge/68Ga Generators and 68Ga Radiopharmaceutical Chemistry on Their Way into a New Century. J Postgrad Med Edu Res 2013;47(1):18-25.

An HPLC and UHPLC-HRMS approach to study PSMA-11 instability in aqueous solution

“…A series of modifications to the original radiosynthesis procedure was performed to investigate the possibility to reduce the risk of low radiolabeling yields due to the formation of side product in the aqueous solution of PSMA-11 synthesis precursor: Using only freshly prepared aqueous solutions of PSMA-11 synthesis precursor (maximum 3 days from the preparation); Replacing the Agilent SCX cartridge, included in the reagent kit (SCX reagent kit for the [ 68 Ga]Ga- labeling of peptides) for the trapping and the purification of [ 68 Ga]GaCl 3 eluted (Dunstone and Payne 1959 ; Eder et al 2012 ; Roesch 2013 ) , with a Phenomenex SCX cartridge that shows greater affinity for metal impurities, to minimize the presence in the reactor of metal ions from the [ 68 Ga]GaCl 3 eluate; Increasing the amount of PSMA-11 precursor from 10 μ g aliquots to 30 μ g aliquots according to Ph. Eur.…”

“…[ 68 Ga]Ga-PSMA-11 radiosynthesis Radiosynthesis of [ 68 Ga]Ga-PSMA-11 was carried out according to a well-established method (Dunstone and Payne 1959;Eder et al 2012;Roesch 2013).…”

Production and separation of 43Sc for radiopharmaceutical purposes

“…The radiometal 68 Ga achieved an important role in oncological PET (Banerjee and Pomper 2013 , Velikyan 2014 ), as its decay characteristics (T 1/2 = 68 min, Eβ + av = 830 keV, [89%]) allow the acquisition of high quality images, for example, the visualization of neuroendocrine tumors and their metastases by 68 Ga-labeled somatostatin analogues, as demonstrated in a number of clinical studies (Gabriel et al 2007 , Kwekkeboom et al 2010 ). The commercial 68 Ge/ 68 Ga generator system ensures an easy and flexible availability of 68 Ga, however, only a limited quantity of radioactivity (equivalent to two patient doses when using a new generator) can be obtained per elution (Eppard et al 2013 , Rösch 2013 ). The short half-life of 68 Ga entails a close proximity of the production facility in question, which is obliged to follow the guidelines of good manufacturing practice (GMP) in most countries, to an operating PET scanner (Breeman, et al 2011 ).…”

Synthesis and evaluation of 68Ga‐HBED‐CC‐EDBE‐folate for positron‐emission tomography imaging of overexpressed folate receptors on CT26 tumor cells

“…68 Ga decays into a stable isotope, 68 Zn, through positron emission (89%) and electron capture (11%) processes . A tremendous advantage of 68 Ga is its low cost and facile production by a 68 Ge/ 68 Ga generator, and radiotracers for PET can be synthesized from 68 Ga in the laboratory . A Lewis acid, Ga is classified as a hard acid; it strongly binds ligands or chelators containing Lewis basic N and O donor atoms to form stable complexes .…”