Comparison of Al18F-NOTA-LM3 With 68Ga-DOTATATE and 68Ga-NODAGA-LM3 PET/CT in Patients With Well-differentiated Neuroendocrine Tumors

Официальное название

Evaluation of Biodistribution, Dosimetry, Diagnostic Ability, and Safety of Al18F-NOTA-LM3 in Patients With Well-differentiated Neuroendocrine Tumors, and Comparison With 68Ga-DOTATATE and 68Ga-NODAGA-LM3: A Prospective, Single-center, Double-blinded Study

Обзор

This prospective, single-center, double-blinded study investigates the biodistribution, dosimetry, safety, and diagnostic ability of Al18F-NOTA-LM3 in patients with well-differentiated neuroendocrine tumors. And compares the diagnostic ability of Al18F-NOTA-LM3 with 68Ga-DOTATATE PET/CT and 68Ga-NODAGA-LM3 PET/CT. Clinical management will also be compared using different imaging modalities.

Подробное описание

Somatostatin receptors (SSTR), especially SSTR subtype 2 (SSTR2), are highly expressed in well-differentiated neuroendocrine tumors (NETs). Radiolabeled somatostatin analogs, including 68Ga-DOTATATE, are widely used for NET imaging and play essential roles in primary tumor seeking, staging, as well as management. SSTR antagonists have recently emerged as another type of somatostatin analog and showed better performance than analogs. Our previous studies exhibited better diagnostic efficacy of 68Ga-DOTA-LM3, 68Ga-DOTA-JR11, and 68Ga-NODAGA-LM3 compared to 68Ga-DOTATATE, especially liver metastasis.

18F-labeled radiotracers have shown several advantages compared to 68Ga-labelled tracers, including increased cyclotron production, lower positron energy, and longer half-life when compared to 68Ga, theoretically to the benefit of image quality. The purpose of this study is to investigate the biodistribution, safety, and diagnostic ability of Al18F-NOTA-LM3 in patients with well-differentiated neuroendocrine tumors. And compare the diagnostic ability of Al18F-NOTA-LM3 with 68Ga-DOTATATE PET/CT and 68Ga-NODAGA-LM3 PET/CT. Clinical management related to imaging will also be compared.

Patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) will be recruited in this study. All patients will be randomized into two arms (A and B): Patients in arm A performed Al18F-NOTA-LM3 and 68Ga-DOTATATE. Patients in arm B performed Al18F-NOTA-LM3 and 68Ga-NODAGA-LM3. The first eight patients will undergo serial PET scans at 5, 15, 30, 45, 60, and 120 min after injection of Al18F-NOTA-LM3. The following patients will perform a whole-body PET/CT scan at 60-90 minutes after injection of Al18F-NOTA-LM3. All patients a whole-body PET/CT scan at 40-60 minutes after administering 68Ga-DOTATATE or 68Ga-NODAGA-LM3. For each patient, the two pet scans should be done within a week and the interval between the two scans should be at least 24h in case of mutual interference.

The images were reviewed by 2 experienced nuclear medicine physicians who were masked to all patients' clinical information. The results were based on consensus, with any discrepant result resolved by a consensus image interpretation by a third senior physician.

The biodistribution, dosimetry, safety, and diagnostic ability of Al18F-NOTA-LM3 will be explored. The diagnostic ability of Al18F-NOTA-LM3 with 68Ga-DOTATATE PET/CT and 68Ga-NODAGA-LM3 PET/CT will be compared. We will also compare the clinical management using different imaging modalities.

Вмешательства

• Диагностический тест Al18F-NOTA-LM3
  40 patients will be enrolled in this arm. The first enrolled 8 patients will undergo serial whole-body PET/CT scans at multiple time points (5, 15, 30, 45, 60, and 120 min) after injection of Al18F-NOTA-LM3. The following patients will undergo a whole-body PET/CT scan 60-120 minutes after injection.
• Диагностический тест 68Ga-DOTATATE
  All patients in arm A will undergo a whole-body PET/CT scan 40-60 minutes after injection of 68Ga-DOTATATE. 68Ga-DOTATATE PET/CT and Al18F-NOTA-LM3 PET/CT should be performed within a week and the interval between the two scans at least 24h.
• Диагностический тест Al18F-NOTA-LM3
  40 patients will be enrolled in this arm. All patients will undergo a whole-body PET/CT scan 60-120 minutes after injection.
• Диагностический тест 68Ga-NODAGA-LM3
  All patients in arm B will undergo a whole-body PET/CT scan 40-60 minutes after injection of 68Ga-NODAGA-LM3. 68Ga-NODAGA-LM3 PET/CT and Al18F-NOTA-LM3 PET/CT should be performed within a week and the interval between the two scans at least 24h.

Первичные конечные точки

• Safety of Al18F-NOTA-LM3 [Срок оценки: From radiotracer injection to 24 hours post-injection.]
• Detection rate of Al18F-NOTA-LM3 on per-patient basis [Срок оценки: From study completion to 6 months after completion.]
• SUVmax of lesions detected on Al18F-NOTA-LM3 PET/CT [Срок оценки: From study completion to 6 months after completion.]
• Detection rate of 68Ga-DOTATATE on per-patient basis [Срок оценки: From study completion to 6 months after completion.]
• SUVmax of lesions detected on 68Ga-DOTATATE PET/CT [Срок оценки: From study completion to 6 months after completion.]
• Detection rate of 68Ga-NODAGA-LM3 on per-patient basis [Срок оценки: From study completion to 6 months after completion.]
• SUVmax of lesions detected on 68Ga-NODAGA-LM3 PET/CT [Срок оценки: From study completion to 6 months after completion.]

Вторичные конечные точки (2)

• SUVmax of normal organs [Срок оценки: From study completion to 6 months after completion.]
• Absorbed dose of target organs [Срок оценки: From study completion to 6 months after completion.]

Критерии участия

Критерии включения

• Patients aged 18 to 80 years.
• Histologically proven, well-differentiated, NETs (G1 or G2).
• No long-acting somatostatin analog treatment within 4 weeks.
• No PRRT treatment within 8 weeks.

Критерии исключения

• Combined with other types of tumors.
• Severe liver or renal dysfunction (ALT/AST≥5 ULN, GFR<30ml/min).
• Active infection.
• Pregnant or breast-feeding women.
• Inability to perform PET/CT scans.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Диагностика

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Публикации

• Liu M, Zhang Y, Yan X, Zhang H, Ren C, Huang Z, Cheng Y, Xu Q, Li Y, Jia R, Zhu W, Huo L. Assessment of the diagnostic efficacy and clinical significance of [18F]AlF-NOTA-LM3 PET/CT in patients with well-differentiated neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2026 Jan;53(2):954-967. doi: 10.1007/s00259-025-07484-9. Epub 2025 Aug 5. PMID 40762797
• Liu M, Ren C, Zhang H, Zhang Y, Huang Z, Jia R, Cheng Y, Bai C, Xu Q, Zhu W, Huo L. Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial. Eur J Nucl Med Mol Imaging. 2024 Oct;51(12):3719-3730. doi: 10.1007/s00259-024-06790-y. PMID 38878175

Идентификаторы

NCT: NCT06056362 · ALFLM3NET

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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