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

TL;DR

This pilot study explores whether hypoxia explains the 'DONUT' phenomenon in neuroendocrine tumors using [18F]FMISO PET scans.

Contribution

The study introduces dynamic [18F]FMISO imaging to evaluate hypoxia in DONUT lesions of metastatic neuroendocrine tumors.

Findings

Dynamic [18F]FMISO imaging showed increased uptake in DONUT lesions for 8 out of 10 patients.

Only one patient showed [18F]FMISO uptake greater than normal liver on delayed static imaging.

Dynamic imaging is suggested as more effective than static imaging for detecting hypoxia in these lesions.

Abstract

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.

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