A novel molecular imaging technique using [⁶⁸Ga]Ga-mDesmo PET-CT for localizing tumors in Cushing's disease.

Abstract

Localizing the source of adrenocorticotropic hormone (ACTH) in patients with ACTH-dependent Cushing's syndrome (CS) poses significant challenges. There is a pressing need for novel imaging modalities that provide both anatomical delineation and functional confirmation of corticotropinomas. This study utilized a modified form of desmopressin (mDesmo), an agonist of the V1b receptor, which is overexpressed in tumoral corticotrophs. After modification, radionuclide ⁶⁸Ga was chelated to produce a new radiopharmaceutical for positron emission tomography (PET) imaging. A total of 234 patients with CS were screened and 30 underwent [⁶⁸Ga]Ga-mDesmo imaging. Patient demographics and hormonal levels (plasma cortisol and ACTH) were recorded, and the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) and [⁶⁸Ga]Ga-mDesmo was compared, with histopathological evidence of a corticotropinoma serving as the reference standard. The cohort comprised 10 males (33%, CI: 16-50%) and 20 females (67%, CI: 50-84), with a mean age of 33.5 ± 13.5 years. Of 30 patients with CS, 24 patients had treatment naïve Cushing's disease (CD) of which 17 (71%, CI: 53-89%) had microadenomas and 7 (30%, CI: 12-48%) had macroadenoma; 4 (13%, CI: 0-25%) patients had ectopic Cushing syndrome (ECS). CE-MRI identified lesions in 16 patients (67%, CI: 48-86%), while [⁶⁸Ga]Ga-mDesmo successfully identified corticotropinomas in all 24 patients (100%, CI: 86-100%). In patients with microadenomas, CE-MRI had a diagnostic accuracy of 53% (CI: 29-77%), whereas [⁶⁸Ga]Ga-mDesmo achieved 100% (CI: 86-100%). There was no uptake of [⁶⁸Ga]Ga-mDesmo in the pituitary of patients with ECS. This study demonstrates that [⁶⁸Ga]Ga-mDesmo imaging is an effective in vivo molecular imaging technique for delineating corticotropinomas, surpassing the accuracy of CE-MRI and BIPSS, regardless of adenoma size. CTRI/2022/08/044615 dated 03/08/2022.