Pauwels Elin, Cleeren Frederik, Tshibangu Térence, Koole Michel, Serdons Kim, Dekervel Jeroen, Van Cutsem Eric, Verslype Chris, Van Laere Koen, Bormans Guy, Deroose Christophe M
Nuclear Medicine, University Hospitals Leuven, Campus Gasthuisberg, Herestraat 49, BE-3000, Leuven, Belgium.
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3033-3046. doi: 10.1007/s00259-020-04918-4. Epub 2020 Jul 2.
The widespread use of gallium-68-labelled somatostatin analogue (SSA) PET, the current standard for somatostatin receptor (SSTR) imaging, is limited by practical and economic challenges that could be overcome by a fluorine-18-labelled alternative, such as the recently introduced [F]AlF-NOTA-octreotide ([F]AlF-OC). This prospective trial aimed to evaluate safety, dosimetry, biodistribution, pharmacokinetics and lesion targeting of [F]AlF-OC and perform the first comparison with [Ga]Ga-DOTATATE in neuroendocrine tumour (NET) patients.
Six healthy volunteers and six NET patients with a previous clinical [Ga]Ga-DOTATATE PET were injected with an IV bolus of 4 MBq/kg [F]AlF-OC. Healthy volunteers underwent serial whole-body PET scans from time of tracer injection up to 90 min post-injection, with an additional PET/CT at 150 and 300 min post-injection. In patients, a 45-min dynamic PET was acquired and three whole-body PET scans at 60, 90 and 180 min post-injection. Absorbed organ doses and effective doses were calculated using OLINDA/EXM. Normal organ uptake (SUV) and tumour lesion uptake (SUV and tumour-to-background ratio (TBR)) were measured. A lesion-by-lesion analysis was performed and the detection ratio (DR), defined as the fraction of detected lesions was determined for each tracer.
[F]AlF-OC administration was safe and well tolerated. The highest dose was received by the spleen (0.159 ± 0.062 mGy/MBq), followed by the urinary bladder wall (0.135 ± 0.046 mGy/mBq) and the kidneys (0.070 ± 0.018 mGy/MBq), in accordance with the expected SSTR-specific uptake in the spleen and renal excretion of the tracer. The effective dose was 22.4 ± 4.4 μSv/MBq. The physiologic uptake pattern of [F]AlF-OC was comparable to [Ga]Ga-DOTATATE. Mean tumour SUV was lower for [F]AlF-OC (12.3 ± 6.5 at 2 h post-injection vs. 18.3 ± 9.5; p = 0.03). However, no significant differences were found in TBR (9.8 ± 6.7 at 2 h post-injection vs. 13.6 ± 11.8; p = 0.35). DR was high and comparable for both tracers (86.0% for [Ga]Ga-DOTATATE vs. 90.1% for [F]AlF-OC at 2 h post-injection; p = 0.68).
[F]AlF-OC shows favourable kinetic and imaging characteristics in patients that warrant further head-to-head comparison to validate [F]AlF-OC as a fluorine-18-labelled alternative for gallium-68-labelled SSA clinical PET.
Clinicaltrials.gov : NCT03883776, EudraCT: 2018-002827-40.
镓-68标记的生长抑素类似物（SSA）PET作为生长抑素受体（SSTR）成像的当前标准，其广泛应用受到实际和经济挑战的限制，而氟-18标记的替代物，如最近推出的[F]AlF-NOTA-奥曲肽（[F]AlF-OC），可能克服这些挑战。这项前瞻性试验旨在评估[F]AlF-OC的安全性、剂量学、生物分布、药代动力学和病变靶向性，并在神经内分泌肿瘤（NET）患者中首次与[Ga]Ga- DOTATATE进行比较。
6名健康志愿者和6名先前接受过临床[Ga]Ga- DOTATATE PET检查的NET患者静脉推注4 MBq/kg的[F]AlF-OC。健康志愿者在注射示踪剂后至注射后90分钟进行系列全身PET扫描，在注射后150和300分钟进行额外的PET/CT扫描。在患者中，采集45分钟的动态PET图像，并在注射后60、90和180分钟进行三次全身PET扫描。使用OLINDA/EXM计算吸收器官剂量和有效剂量。测量正常器官摄取（SUV）和肿瘤病变摄取（SUV和肿瘤与背景比值（TBR））。进行逐病变分析，并确定每种示踪剂的检测率（DR），定义为检测到的病变比例。
[F]AlF-OC给药安全且耐受性良好。脾脏接受的剂量最高（0.159±0.062 mGy/MBq），其次是膀胱壁（0.135±0.046 mGy/mBq）和肾脏（0.070±0.018 mGy/MBq），这与脾脏中预期的SSTR特异性摄取和示踪剂的肾脏排泄一致。有效剂量为22.4±4.4 μSv/MBq。[F]AlF-OC的生理摄取模式与[Ga]Ga- DOTATATE相当。[F]AlF-OC的平均肿瘤SUV较低（注射后2小时为12.3±6.5，而[Ga]Ga- DOTATATE为18.3±9.5；p = 0.03）。然而，TBR无显著差异（注射后2小时为9.8±6.7，而[Ga]Ga- DOTATATE为13.6±11.8；p = 0.35）。两种示踪剂的DR都很高且相当（注射后2小时，[Ga]Ga- DOTATATE为86.0%，[F]AlF-OC为90.1%；p = 0.68）。
[F]AlF-OC在患者中显示出良好的动力学和成像特征，值得进一步进行直接比较，以验证[F]AlF-OC作为镓-68标记的SSA临床PET的氟-18标记替代物。
Clinicaltrials.gov：NCT038837`76，EudraCT：2018-002827-40。
