[¹⁸F]FMISO PET in metastatic neuroendocrine tumours: a pilot study

The phenomenon of peripheral [⁶⁸Ga]DOTATATE avidity without central avidity (which we have termed a "DONUT") has been observed in neuroendocrine neoplasm (NEN) lesions. There has been speculation as to whether this is due to hypoxia, de-differentiated disease or other causes. The presence of hypoxia may have prognostic and therapeutic implications, and was evaluated in these lesions using the PET hypoxia imaging biomarker [¹⁸F]FMISO.

Prospective pilot study in patients with metastatic NENs with at least one DONUT lesion (central [⁶⁸Ga]DOTATATE non-avidity). [¹⁸F]FDG and [¹⁸F]FMISO scans were acquired within 60 days of the [⁶⁸Ga]DOTATATE PET/CT. [¹⁸F]FMISO scans were acquired as a dynamic scan over 20 mins from injection with a delayed image at 2 hours. The dynamic acquisition was analysed quantitatively using a graphical approach yielding parametric images of Influx Rate Constant and Volume of Distribution. [¹⁸F]FMISO uptake within the identified DONUT hole on the 2 hr delayed scan was qualitatively scored by two experienced nuclear medicine physicians as: 0 (no uptake), 1 (uptake less than normal liver), 2 (uptake equal to normal liver), or 3 (uptake greater than normal liver).

Ten patients were enrolled with primary sites including pancreas (n=3), small bowel (n=3), rectum (n=2), duodenum (n=1) and lung (n=1). Six subjects were scored 1, three subjects were scored 2, and one subject was scored 3. All lesions evaluated were located in the liver. Quantitative [¹⁸F]FMISO parametric imaging showed evidence of increased uptake rate (Ki) in the photopenic areas of the DONUT lesions in 8/10 subjects. Surrounding uptake rate in normal liver was extremely low. In the qualitative delayed image assessment, only one subject demonstrated [¹⁸F]FMISO uptake greater than surrounding normal liver (small bowel primary, G2).

Only one of ten patients with DONUT lesions demonstrated increased [¹⁸F]FMISO uptake rate on delayed static imaging. In contrast, dynamic imaging demonstrated increased [¹⁸F]FMISO uptake rate in the region of [⁶⁸Ga]DOTATATE photopenia on 8 of 10 patients. Future research using [¹⁸F]FMISO in NEN patients should incorporate dynamic imaging.