Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

Abstract

Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([68Ga]DOTAGA, Tyr3, Thr8) octreotide ([68Ga]DOTAGA-TATE) and ([68Ga]DOTAGA, Tyr3) octreotide ([68Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [68Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1h post-injection (p.i.). [68Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170MBq, 1h p.i.) with histologically confirmed well-differentiated NETs. [68Ga]DOTAGA-TATE exhibited hydrophilicity similar to [68Ga]DOTA-TATE (log P=-3.51 vs -3.69) whereas [68Ga]DOTAGA-TOC was more hydrophilic than [68Ga]DOTA-TOC (log P=-3.27 vs -2.93). [68Ga]DOTAGA-TATE and [68Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p<0.05) of [68Ga]DOTAGA-TATE was observed from other non-specific organs (liver, lungs, spleen, intestine). [68Ga]DOTAGA-TOC also demonstrated rapid clearance from blood and kidneys (p<0.05) in comparison to [68Ga]DOTA-TOC. The metastatic lesions in NET patients were well identified by [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC. The phenomenal analogy was observed between [68Ga]DOTAGA-TATE and [68Ga]DOTA-TATE as well as between [68Ga]DOTAGA-TOC and [68Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.