Head-to-Head comparison of [¹⁸F]AlF-NOTA-TATE and [⁶⁸Ga]Ga-DOTA-TATE PET/CT in patients with neuroendocrine tumors: a prospective study.

Abstract

A prospective comparison was conducted between [¹⁸F]AlF-NOTA-TATE and the routinely used clinical imaging agent [⁶⁸Ga]Ga-DOTA-TATE in patients with neuroendocrine tumors (NETs) to evaluate diagnostic performance, pharmacokinetic characteristics, and safety. Additionally, the clinical potential of [¹⁸F]AlF-NOTA-TATE as an alternative imaging agent was explored. [¹⁸F]AlF-NOTA-TATE was synthesized automatically using a self-developed direct purification technology based on column chromatography, with strict adherence to quality control standards. A clinical comparative study enrolled 20 patients with suspected or confirmed neuroendocrine tumors (NETs) (median age: 52 years). All patients underwent PET/CT imaging with both [¹⁸F]AlF-NOTA-TATE (7.8 ± 1.8 mCi) and [⁶⁸Ga]Ga-DOTA-TATE (3.9 ± 0.6 mCi) within a 3-day interval. Image analysis included evaluation of parameters such as lesion detection rate, maximum standardized uptake value (SUVmax), and tumor-to-background ratio (TBR). In parallel, radiation dosimetry and biodistribution characteristics were also assessed. Among the 20 patients, 13 were diagnosed with NETs, 4 exhibited negative imaging findings, and 3 had non-NET lesions. Biodistribution analysis revealed that [¹⁸F]AlF-NOTA-TATE showed higher physiological uptake in normal organs such as the pituitary gland and spleen compared to [⁶⁸Ga]Ga-DOTA-TATE, but lower uptake in the brain and blood pool. The overall lesion detection rates of [¹⁸F]AlF-NOTA-TATE and [⁶⁸Ga]Ga-DOTA-TATE in pancreas, liver, lymph nodes and bone metastases were consistent; however, [¹⁸F]AlF-NOTA-TATE demonstrated significantly higher uptake in liver metastases (SUVmax: 63.9 ± 24.9 vs. 37.2 ± 6.2, P = 0.009), lymph node metastases (median SUVmax: 33.8 vs. 22.4, P = 0.021), and bone metastases (SUVmax: 112.9 ± 20.7 vs. 66.1 ± 6.7, P < 0.001). In terms of tumor-to-background ratio (TBR), [¹⁸F]AlF-NOTA-TATE also outperformed [⁶⁸Ga]Ga-DOTA-TATE for liver lesions (77.8 ± 32.4 vs. 57.3 ± 17.6, P = 0.040) and bone metastases (135.2 ± 28.6 vs. 89.3 ± 18.9, P = 0.001). Dosimetry analysis indicated an effective dose of 0.021 ± 0.007 mSv/MBq, with the spleen receiving the highest absorbed dose (0.109 ± 0.059 mGy/MBq), and confirmed good safety. [¹⁸F]AlF-NOTA-TATE demonstrated a comparable lesion detection rate to [⁶⁸Ga]Ga-DOTA-TATE for the diagnosis of neuroendocrine tumors (NETs), while exhibiting higher tumor uptake and superior tumor-to-background ratios (TBR). These results suggest that [¹⁸F]AlF-NOTA-TATE may serve as a promising alternative for the diagnosis of NETs. Chinese Clinical Trial Registry (ChiCTR2300072266), registered on 8 June 2023.