In vitro binding affinities and initial in vivo evaluation of Ga-68-DATA-TOC

Objectives The novel DATA (6-Amino-1,4-diazepine-triacetate) chelator is the choice for kit-type labelling of Ga-68-radiopharmaceuticals. Ga-68-DATATOC labelling was verified in quantitative yields at room temperature and low amounts of precursor, making purification steps obsolete. The aim of this study was to investigate if receptor-affinity parameters as well as pharmacology in humans are similar for Ga-68-DATATOC and the known PET-tracer Ga-68-DOTATOC.

Methods Ga-67/69-DATATOC and Ga-67/69-DOTATOC have been synthesised and purified by HPLC. Competition binding experiments were performed in cell membranes of HEK293 cells transfected to stably express one of the human somatostatin receptor subtypes 2, 3, or 5 (hsst2,3,5). I-125-[LTT]SS28) served as competing radioligand and [LTT]SS28 as reference compound. Ga-68-DATATOC and Ga-68-DOTATOC were used to quantify SUV values for all organs of a 46 y.o. male with well-differentiated functional neuroendocrine neoplasm of the pancreatic body and tail with involvement of the stomach, spleen and adrenal gland, and lymph node metastases.

Results IC50 values in nM of Ga-67/69-DATATOC were 1.03 (±0.08) nM, 125 (±22.0) nM and 96.0 (±23.0) nM for hsst2, hsst3 and hsst5, respectively. The corresponding values for Ga-67/69-DOTATOC were 0.21 (±0.01) nM, 123 (±51.0) nM and 45.0 (±10.2) nM. First human PET-imaging results showed that SUV values were comparable for both tracers. Notably, the uptake in the liver was much less for Ga-68-DATATOC, and tumour-to-liver ratios were 9 compared to 23 for Ga-68-DOTATOC.

Conclusions In conclusion, both in vitro hsst2,3,5-binding affinity profile and pharmacology in human were comparable for Ga-68-DATATOC and Ga-68-DOTATOC. Findings of the present study highlight the promising qualities of Ga-68-DATATOC for routine clinical application owing to a particularly convenient kit-type labelling protocol.