Preparation and Preliminary Clinical Application of [18F]AlF-NOTA-TATE

Abstract

68Ga-DOTA-TATE has been successfully applied in the diagnosis of clinical neuroendocrine tumors，but its short half-life limits its widespread use. This study aimed to develop [18F]AlF-NOTA-TATE to meet the clinical demands of patients with neuroendocrine tumors (NETs) for diagnosis and treatment evaluation. A new column chromatography purification method for [18F]AlF-NOTA-TATE was developed and automated synthesis was performed using a clinical single-vessel multi-functional fluorine synthesis module. The lipophilicity, in vitro stability，and pharmacokinetics of [18F]AlF-NOTA-TATE were studied，and biodistribution experiments and PET/CT imaging of nude mice with NCI-H69 (SSTR2 positive expression) small cell lung cancer were conducted，followed by preliminary clinical evaluation on three patients with neuroendocrine tumors. The new column chromatography purification method for [18F]AlF-NOTA-TATE was simple，which was synthesized in a short time with higher than 95% of radiochemical purity and，less than 3% of.ethanol content. Pharmacokinetic and biodistribution experiments in BALB/c mice showed rapid blood clearance of the drug and renal metabolism. PET/CT imaging of tumor-bearing mice showed specific uptake of the radiotracer in SSTR-positive tumors. Preliminary clinical application showed that [18F]AlF-NOTA-TATE is well targeted in patients with long retention time and can provide better image quality. The column chromatography method for the preparation of [18F]AlF-NOTA-TATE was simple and had high radiochemical purity. Preliminary clinical results suggested that [18F]AlF-NOTA-TATE has further value for clinical research.

Keywords

• [18f]alf-nota-tate
• column color layer purification
• neuroendocrine tumors
• clinical application