Chan David L, Conner Alice, Pavlakis Nick, Bailey Elizabeth, Aslani Alireza, Willowson Kathy, Diakos Connie, Bernard Elizabeth J, Clarke Stephen, Engel Alexander, Roach Paul J, Bailey Dale L
Faculty of Medicine and Health, University of Sydney, Camperdown, Australia and Department of Medical Oncology, Royal North Shore Hospital, St Leonards, Australia.
Faculty of Medicine and Health, University of Sydney, Camperdown, Australia.
Asia Ocean J Nucl Med Biol. 2025;13(2):117-125. doi: 10.22038/aojnmb.2025.83664.1611.
The phenomenon of peripheral [Ga]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 [F]FMISO.
Prospective pilot study in patients with metastatic NENs with at least one DONUT lesion (central [Ga]DOTATATE non-avidity). [F]FDG and [F]FMISO scans were acquired within 60 days of the [Ga]DOTATATE PET/CT. [F]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. [F]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 [F]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 [F]FMISO uptake greater than surrounding normal liver (small bowel primary, G2).
Only one of ten patients with DONUT lesions demonstrated increased [F]FMISO uptake rate on delayed static imaging. In contrast, dynamic imaging demonstrated increased [F]FMISO uptake rate in the region of [Ga]DOTATATE photopenia on 8 of 10 patients. Future research using [F]FMISO in NEN patients should incorporate dynamic imaging.
在神经内分泌肿瘤（NEN）病变中观察到了外周[镓] DOTATATE摄取而中央无摄取的现象（我们称之为“甜甜圈”现象）。对于其原因是缺氧、去分化疾病还是其他因素，一直存在猜测。缺氧的存在可能具有预后和治疗意义，因此使用PET缺氧成像生物标志物[氟] FMISO对这些病变进行了评估。
对患有转移性NEN且至少有一个“甜甜圈”病变（中央[镓] DOTATATE无摄取）的患者进行前瞻性试点研究。在[镓] DOTATATE PET/CT检查的60天内进行了[氟] FDG和[氟] FMISO扫描。[氟] FMISO扫描通过动态扫描进行，注射后20分钟内完成，2小时后有延迟图像。使用图形方法对动态采集数据进行定量分析，得出流入速率常数和分布容积的参数图像。在2小时延迟扫描中，由两位经验丰富的核医学医师对已识别的“甜甜圈”空洞内的[氟] FMISO摄取进行定性评分：0（无摄取）、1（摄取低于正常肝脏）、2（摄取等于正常肝脏）或3（摄取高于正常肝脏）。
共纳入10例患者，原发部位包括胰腺（n = 3）、小肠（n = 3）、直肠（n = 2）、十二指肠（n = 1）和肺（n = 1）。6名受试者评分为1分，3名受试者评分为2分，1名受试者评分为3分。所有评估的病变均位于肝脏。定量[氟] FMISO参数成像显示，10名受试者中有8名在“甜甜圈”病变的放射性缺损区域摄取率（Ki）增加。正常肝脏周围的摄取率极低。在定性延迟图像评估中，只有一名受试者（小肠原发，G2）的[氟] FMISO摄取高于周围正常肝脏。
10例有“甜甜圈”病变的患者中，只有1例在延迟静态成像中显示[氟] FMISO摄取率增加。相比之下，动态成像显示10例患者中有8例在[镓] DOTATATE放射性缺损区域的[氟] FMISO摄取率增加。未来在NEN患者中使用[氟] FMISO的研究应纳入动态成像。
