Prospective Evaluation of 18F‑Fluoroethyltyrosine PET Positivity in Adults with de novo or Recurrent Functional Pituitary Adenomas and Indeterminate MRI

18FET PET will be used to estimate the functional pituitary adenoma positivity rate in adults with de novo, recurrent, or persistent disease and indeterminate pituitary MRI, to identify patients suitable for adenoma‑targeted surgery or external beam radiation therapy. Secondary objectives include:

• Proportion of PET‑positive patients who receive adenoma‑targeted treatment within 12 months.
• Proportion of PET‑negative patients who undergo exploratory surgery within 12 months.
• Response rate among patients undergoing surgery (adenoma‑targeted for PET‑positive and exploratory for PET‑negative) during the 12‑month period.
• Quantitative PET parameters (SUVmax, SUVmean, SUVpeak, adenoma‑to‑brain ratios, activity‑time curve, time to peak) in PET‑positive cases.
• Correlation of PET findings with histological subtypes of the adenoma.
• Inter‑reader reproducibility of PET positivity interpretation.

The sponsor did not provide information on the total number of participants. The trial enrolled adult men and women, each aged ≥ 18 years, who presented with a suspected functional pituitary adenoma (including prolactinoma, Cushing’s disease, acromegaly, or thyrotropic adenoma), either newly diagnosed or with recurrence/persistence, and who had an indeterminate pituitary MRI. All subjects were required to be covered by social security, eligible for surgery and/or external beam radiation therapy should 18FET PET prove positive, and willing to comply with study procedures for the study duration. The population comprised patients of both sexes without restriction based on vulnerability status, and selection was based on meeting the specified inclusion criteria; no specific lifestyle factors such as diet or physical activity were stipulated.

The study is a prospective, single‑center, single‑arm, phase IV trial evaluating the diagnostic contribution of 18F‑fluoro‑ethyl‑tyrosine PET in adults with suspected functional pituitary adenoma and indeterminate pituitary MRI; no randomization, blinding, or control arm is employed. After an initial screening visit to confirm eligibility, participants receive an intravenous injection of 250 MBq of the radiotracer followed by a PET scan (baseline visit). Subsequent follow‑up visits are scheduled at approximately 3, 6, and 12 months to document any adenoma‑targeted interventions (surgery or external beam radiation), assess laboratory response, and record imaging parameters. The end‑of‑study visit occurs at 12 months, concluding the participant’s involvement, which therefore spans roughly one year from enrollment. Early termination may occur if a participant withdraws consent, experiences a serious adverse event related to the investigational product, or is found to be ineligible after the screening assessment.

IASOglio 2 GBq/mL, solution injectable, containing fluoroethyltyrosine f-18 as the active radiopharmaceutical, is administered as a single intravenous injection of 250 MBq. The preparation is supplied as a sterile solution for injection and is given once per imaging session. The dose is fixed, and the administration occurs prior to the scheduled PET scan in accordance with the diagnostic protocol.

No non‑experimental therapeutic agents, placebo, or comparator treatments are provided in this single‑arm study. Study conduct relies exclusively on the diagnostic imaging performed with the radiotracer, and compliance monitoring includes verification of the injection time, documentation of the administered activity, and confirmation of completion of the PET acquisition.

Efficacy assessment is based on imaging and clinical response parameters. The primary efficacy parameter is the prevalence of patients with positive 18FET PET, defined by consensus of three independent readers as focal hyperuptake exceeding the intensity of normal cerebral and pituitary background. Secondary efficacy parameters include: the proportion of patients with a positive scan who receive adenoma‑targeted therapy (surgery and/or external beam radiation) within the 12‑month observation period; the proportion of patients with a negative scan who undergo exploratory surgery during the same period; the proportion of surgically treated patients who achieve improvement or normalization of laboratory values specific to the histological subtype; quantitative PET metrics such as SUVmax, SUVmean, SUVpeak, the ratios of adenoma to healthy brain tissue for SUVmax and SUVmean, and kinetic parameters (activity‑time curve, time to peak); analysis of PET results stratified by histological subtype using the same quantitative metrics; and the level of inter‑reader agreement measured by Krippendorff’s alpha coefficient.

Imaging assessments are performed using a standardized 18F‑fluoro‑ethyl‑tyrosine PET protocol with intravenous administration of 250 MBq of the radiotracer. Images are acquired according to validated PET acquisition parameters, and quantitative values (SUVmax, SUVmean, SUVpeak, ratios, and kinetic data) are derived using dedicated image‑analysis software. Three blinded readers independently evaluate each scan for positivity; consensus is reached through a predefined adjudication process. Clinical laboratory parameters are collected at baseline and at scheduled follow‑up visits throughout the 12‑month study period to determine treatment response. All data are analyzed descriptively, with prevalence and proportion outcomes expressed as percentages, and inter‑reader reliability reported using the calculated Krippendorff’s alpha.