¹⁸F-AlF-NOTA-octreotide PET/CT in high-grade G3 neuroendocrine tumors and neuroendocrine carcinomas: diagnostic...

Radiolabeled somatostatin receptor (SSTR) analogues are widely utilized for both imaging (PET or scintigraphy) and peptide receptor radionuclide therapy (PRRT) in the management of neuroendocrine neoplasms (NENs). These approaches have been extensively validated in low- to intermediate-grade gastroenteropancreatic neuroendocrine tumors (NET G1 - G2). However, data on the use of SSTR imaging - particularly SSTR PET imaging - in patients with high-grade NETs (G3) and neuroendocrine carcinomas (NECs) remain limited. This study aimed to evaluate the diagnostic performance of ¹⁸F-AlF-NOTA-octreotide (¹⁸F-AlF-OC) PET/CT in patients with high-grade NENs and assess its complementarity with ¹⁸F-FDG PET/CT.

Out of 426 patients who underwent ¹⁸F-AlF-OC PET/CT between January 2023 and October 2024, 42 patients with histologically confirmed high-grade NENs (28 with G3 NETs and 14 with NECs) were retrospectively analyzed. 36 patients also underwent ¹⁸F-FDG PET/CT. Lesions were classified as positive on PET/CT if their uptake exceeded organ background activity and could not be explained by physiologic biodistribution. Tumor uptake higher than normal liver was considered high uptake.

On a per-patient basis, ¹⁸F-AlF-OC PET/CT was positive in 39 of 42 patients, yielding a detection rate of 92.9%. Among all patients, 28 (66.7%, 28/42) exhibited high ¹⁸F-AlF-OC uptake, and 19 (45.2%, 19/42) demonstrated positivity in all lesions. Of the 36 patients who underwent both scans, detection rates were 91.7% (33/36) for ¹⁸F-AlF-OC and 88.9% (32/36) for ¹⁸F-FDG PET/CT. Discordant findings were observed in 11 patients (30.6%) with¹⁸F-AlF-OC-negative/¹⁸F-FDG-positive lesions and in 13 patients (36.1%) with ¹⁸F-AlF-OC-positive/¹⁸F-FDG-negative lesions. On a per-lesion basis, ¹⁸F-AlF-OC PET/CT showed a higher detection rate than ¹⁸F-FDG PET/CT (80.7% [547/678] vs. 72.9% [494/678]). Specifically, ¹⁸F-AlF-OC identified 109 lesions missed by ¹⁸F-FDG, while ¹⁸F-FDG identified 56 lesions missed by ¹⁸F-AlF-OC. The combined use of both tracers improved the detection rate to 89.1% (604/678), surpassing either modality alone.

¹⁸F-AlF-OC PET/CT demonstrated high detection rates in patients with high-grade NENs, with a substantial proportion showing strong SSTR expression and lesion-wide positivity, supporting its potential role in guiding PRRT eligibility. The complementary nature of ¹⁸F-AlF-OC and ¹⁸F-FDG PET/CT enhances overall diagnostic accuracy, making dual-tracer imaging a valuable approach in this setting.