Physiological Animal Imaging with 68Ga-Citrate

Abstract

: Gallium-68 is an ideal research and hospital-based PET radioisotope. The uptake mechanism of Gallium citrate is a combination of specific and non-specific processes, for example, vasodilatation, increased vascular permeability, plasma transferrin binding and lactoferrin and siderophores. In this study, by applying the 68Ge/68Ga generator product, a simple technique for the synthesis and quality control of 68Ga-citrate was introduced and was followed by preliminary animal studies. The synthesis of 68Ga-citrate was performed with a cationic method using the Scintomics automated synthesis system (Scintomics GmbH GRP module 4V). Since the standard procedure for quality control (QC) was not available, the definition of chemical and radiochemical purity of 68Ga-citrate was carried out according to the ICH Q2(R1) guideline. The standard QC tests were analysed with Scintomics 8100 radio-HPLC system equipped with a radioactivity detector. In this study, a New Zealand rabbit weighing 2520 g was used for PET/CT images. 68Ga-citrate synthesis was performed by a cationic method without using organic solvents. The labelling efficiency was found to be >98%. The HPLC method used to assess the radiochemical purity of 68Ga -citrate was validated as rapid, accurate and reproducible enough to apply it to patients safely. The physiological distribution of 68Ga-citrate was investigated in a healthy rabbit. The blood pool, liver, spleen, kidneys and growth plates were the most common sites of 68Ga-citrate involvement.

Fully Automated Macro- and Microfluidic Production of [68Ga]Ga-Citrate on mAIO® and iMiDEVTM Modules

“…The mean SUV values obtained for [ 68 Ga]Ga-citrate synthesized on the conventional module and those produced using the microfluidic system were similar, as both ways of production allow the tracer with the same radiochemical properties (volumic activity, radiochemical purity) to be obtained. An accumulation was observed in the heart, liver, and lungs, as was already demonstrated in other works [19,[31][32][33]. Its retention in the blood pool and liver can also be explained, as it is known that 68 Ga can bind iron transport proteins [21,31].…”

“…The radiosynthesis strategy consists in the prepurification of a Ga-68 eluate from potential metal traces by the Zhernosekov method (HCl/Acetone) [18] on a Accell Plus CM cationic cartridge, followed by a labelling in a vessel for 5 min at 70 °C. Recently, Ugur et al used this strategy to produce [ 68 Ga]Ga-citrate on a Scintomics GmbH GRP module 4 V synthesis module by a cationic method of 68 Ga-prepurification (PS-H+ cartridge), followed by labelling in a reactor during 10 min at 70 °C [19]. Overall, the described methods suffer from a potential metal ion impurity breakthrough, the removal of the organic solvent, and the related additional quality control analysis or the prolonged synthesis times because of the heating step.…”

“…As standard method for radiochemical purity control of this radiopharmaceutical, radio-TLC is commonly used, and only few researchers have described the determination of radiochemical purity using HPLC [5,19,21].…”

PET/CT Imaging of Infectious Diseases: Overview of Novel Radiopharmaceuticals

“…The blood pool, liver, spleen, kidneys and growth plates were the most common sites of 68 Ga-citrate involvement [71]. Thus, 68 Ga-citrate is useful for imaging tuberculosis [72]; other feasible applications could be represented by bacterial infections [69,73], periprosthetic joint infections [74], and rheumatoid arthritis [75].…”

“…Conversely, data in the literature about some of 68 Ga-labeled tracers for inflammation and infection are more robust. In particular, 68 Ga-Citrate has already shown the capability to detect bacterial infections [72,74] due to the possibility of being highly enhanced in infectious foci and surrounding tissues, since its binding to transferrin allows the distribution in the infected tissue, which is characterized by high vascular permeability and chemotaxis factors produced by human leukocytes [69,71]. 68 Ga-labeled somatostatin analogues and 68 Ga-FAPI enable visualization of the inflammatory process and infectious foci, although the record of these findings is normally linked to incidental observations during whole-body PET/CT scans performed for oncologic purposes [79], particularly in neuroendocrine tumor patients [86].…”