1. Clinical evaluation of [68Ga]Ga-DATA-TOC in comparison to [68Ga]Ga-DOTA-TOC in patients with neuroendocrine tumours
B Kreppel, J P Sinnes, T Plum, M Essler, H Strunk, E Eppard, R A Bundschuh, F Rösch, F C Gaertner, M Meisenheimer Nucl Med Biol . 2019 Sep-Oct;76-77:1-9. doi: 10.1016/j.nucmedbio.2019.08.006.
Introduction:[68Ga]Ga-DATA-TOC is a new radiolabelled somatostatin-analogue for positron emission tomography (PET) imaging of neuroendocrine tumours. Its advantage over DOTA-conjugated compounds is the possibility for high-efficiency labelling with gallium-68 quickly at room temperature with high reliability and without the need for product purification, which enables the development of an instant kit-type labelling method. We evaluated its imaging characteristics in patients with neuroendocrine tumours in comparison to [68Ga]Ga-DOTA-TOC.Methods:19 patients imaged with [68Ga]Ga-DATA-TOC were retrospectively analysed and uptake in normal tissues was compared with a group of 19 patients imaged with [68Ga]Ga-DOTA-TOC. 10 patients imaged with [68Ga]Ga-DATA-TOC had a history of [68Ga]Ga-DOTA-TOC imaging before and were additionally analysed to obtain biodistribution data of both tracers in the same patients. In 5 patients showing stable disease between both examinations, tumour uptake, lesion detectability and lesion conspicuity of both tracers were evaluated.Results:Uptake of [68Ga]Ga-DATA-TOC in normal organs with expression of the somatostatin receptor was 25-47% lower compared to [68Ga]Ga-DOTA-TOC. Background of [68Ga]Ga-DATA-TOC was 40-41% lower in the liver. A higher retention of [68Ga]Ga-DATA-TOC was observed in the blood (up to 67%) and in the lungs (up to 44%). Tumour uptake (SUV) was 22-31% lower for [68Ga]Ga-DATA-TOC. However, no significant differences were observed for tumour-to-background ratios and lesion detectability. Regarding liver metastases, [68Ga]Ga-DATA-TOC uptake (SUV) reached 69-73% of [68Ga]Ga-DOTA-TOC uptake, but tumour-to-background ratios of [68Ga]Ga-DATA-TOC were 105-110% of [68Ga]Ga-DOTA-TOC ratios. CONCLUSIONS, ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: We demonstrated the feasibility of the new PET tracer [68Ga]Ga-DATA-TOC for imaging of patients with neuroendocrine tumours, showing a comparable performance to [68Ga]Ga-DOTA-TOC. [68Ga]Ga-DATA-TOC has the potential for development of an instant kit-type labelling method at room temperature similar to99mTc-labelled radiopharmaceuticals, which might help to increase the availability of68Ga-labelled somatostatin analogues for clinical routine use.
2. Good practices for 68Ga radiopharmaceutical production
Bryce J B Nelson, Jan D Andersson, Frank Wuest, Sarah Spreckelmeyer EJNMMI Radiopharm Chem . 2022 Oct 22;7(1):27. doi: 10.1186/s41181-022-00180-1.
Background:The radiometal gallium-68 (68Ga) is increasingly used in diagnostic positron emission tomography (PET), with68Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional99mTc agents. In precision medicine, PET applications of68Ga are widespread, with68Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin.Main body:These68Ga radiopharmaceuticals include agents such as [68Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [68Ga]Ga-PLED for assessing renal function, [68Ga]Ga-t-butyl-HBED for assessing liver function, and [68Ga]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (68Ge) generators and cyclotron production routes strongly positions68Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the68Ga radiopharmaceutical community, and recommendations for centers interested in establishing68Ga radiopharmaceutical production.Conclusion:This review outlines important aspects of68Ga radiopharmacy, including68Ga production routes using a68Ge/68Ga generator or medical cyclotron, standardized68Ga radiolabeling methods, quality control procedures for clinical68Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming68Ga radiopharmaceutical production. Finally, an outlook on68Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community.
3. Gibberellin signaling
Lynn M Hartweck Planta . 2008 Dec;229(1):1-13. doi: 10.1007/s00425-008-0830-1.
This review covers recent advances in gibberellin (GA) signaling. GA signaling is now understood to hinge on DELLA proteins. DELLAs negatively regulate GA response by activating the promoters of several genes including Xerico, which upregulates the abscisic acid pathway which is antagonistic to GA. DELLAs also promote transcription of the GA receptor, GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and indirectly regulate GA biosynthesis genes enhancing GA responsiveness and feedback control. A structural analysis of GID1 provides a model for understanding GA signaling. GA binds within a pocket of GID1, changes GID1 conformation and increases the affinity of GID1 for DELLA proteins. GA/GID1/DELLA has increased affinity for an F-Box protein and DELLAs are subsequently degraded via the proteasome. Therefore, GA induces growth through degradation of the DELLAs. The binding of DELLA proteins to three of the PHYTOCHROME INTERACTING FACTOR (PIF) proteins integrates light and GA signaling pathways. This binding prevents PIFs 3, 4, and 5 from functioning as positive transcriptional regulators of growth in the dark. Since PIFs are degraded in light, these PIFs can only function in the combined absence of light and presence of GA. New analyses suggest that GA signaling evolved at the same time or just after the plant vascular system and before plants acquired the capacity for seed reproduction. An analysis of sequences cloned from Physcomitrella suggests that GID1 and DELLAs were the first to evolve but did not initially interact. The more recently diverging spike moss Selaginella has all the genes required for GA biosynthesis and signaling, but the role of GA response in Selaginella physiology remains a mystery.
