Automated production of [18F]SiTATE on a Scintomics GRP™ platform for PET/CT imaging of neuroendocrine tumors

Abstract

Introduction: [¹⁸F]SiTATE (formerly known as [¹⁸F]SiFAlin-TATE) was recently introduced as a highly promising imaging agent for the diagnosis of well-differentiated neuroendocrine tumors (NET) using positron emission tomography/computed tomography (PET/CT). A high tumor uptake and excellent image quality, the straightforward labeling approach, as well as the economic and logistic advantages of ¹⁸F- over ⁶⁸Ga-labeled compounds predestinate [¹⁸F]SiTATE to become a potential new clinical reference standard. A novel state-of-the-art methodology of automated radiopharmaceutical production is required to establish [¹⁸F]SiTATE in clinical routine. This work illustrates the development of a novel synthesis procedure of [¹⁸F]SiTATE on an automated synthesis unit (ASU) and the clinical applicability of the tracer in human NET imaging.

Methods: A new synthesis protocol was generated for the production of [¹⁸F]SiTATE on the Scintomics GRP™ platform for clinical NET imaging. The synthesis was carried out according to common Good Manufacturing Practice (GMP) guidelines including all quality control measurements. To confirm utility, clinical batches (n = 3) were produced and applied to six patients diagnosed with NET.

Results: [¹⁸F]SiTATE was obtained in 54 ± 4% (n = 3) non-decay corrected radiochemical yield (RCY), with a radiochemical purity of 96.3 ± 0.1% and a molar activity (A_m) of 472 ± 45 GBq/μmol (n = 3). Quality control measurements always met the local release criteria. All specifications were taken or adapted from the Ph.Eur. regulations. PET/CT imaging with [¹⁸F]SiTATE produced on the GRP™ module confirmed the expected high image quality. The in vivo distribution pattern and excellent tumor to non-tumor contrast observed, matched the quality of the manually prepared [¹⁸F]SiTATE batches.

Conclusions: The automated manufacture of [¹⁸F]SiTATE was developed using the Scintomics GRP™ platform. The high quality of the radiotracer matched stringent quality control requirements adhering to common GMP guidelines, and its clinical applicability was confirmed by human PET/CT investigations.

Advances in knowledge and implications for patient care: The automated process for the manufacture of [¹⁸F]SiTATE described herein represents an important contribution to make [¹⁸F]SiTATE routinely accessible for its use in clinical NET diagnosis.

Keywords: Automation; GRP™; Neuroendocrine tumors; PET; SiFA; [(18)F]SiTATE.