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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Diagnostic test: Al18F-NOTA-LM3; Diagnostic test: 68Ga-DOTATATE; Diagnostic test: Al18F-NOTA-LM3; Diagnostic test: 68Ga-NODAGA-LM3

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Meixi Liu, MD; Phone Number: +86-15010405355; Email: meixiliu_pumc@126.com
• Study Contact Backup: Name: Li Huo, MD; Phone Number: +86-13910801986; Email: huoli@pumch.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Shuyang Zhang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Al18F-NOTA-LM3 and 68Ga-DOTATATE group; Patients will perform an Al18F-NOTA-LM3 PET/CT as well as a 68Ga-DOTATATE PET/CT.	Diagnostic test: 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.; Diagnostic test: 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.; Diagnostic test: 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.
Experimental: Arm B: Al18F-NOTA-LM3 and 68Ga-NODAGA-LM3 group; Patients will perform an Al18F-NOTA-LM3 PET/CT as well as a 68Ga-NODAGA-LM3 PET/CT.	Diagnostic test: 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.; Diagnostic test: 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.; Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Al18F-NOTA-LM3	Adverse effects were recorded according to CTCAE (version 5.0) after radiotracer injection and PET scan.	From radiotracer injection to 24 hours post-injection.
Detection rate of Al18F-NOTA-LM3 on per-patient basis	Percentage of patients with lesions detected on Al18F-NOTA-LM3 PET/CT.	From study completion to 6 months after completion.
SUVmax of lesions detected on Al18F-NOTA-LM3 PET/CT	The tracer uptake is quantified using maximal standard uptake value (SUVmax) by drawing a 3-dimensional region of interest.	From study completion to 6 months after completion.
Detection rate of 68Ga-DOTATATE on per-patient basis	Percentage of patients with lesions detected on 68Ga-DOTATATE PET/CT.	From study completion to 6 months after completion.
SUVmax of lesions detected on 68Ga-DOTATATE PET/CT	The tracer uptake is quantified using maximal standard uptake value (SUVmax) by drawing a 3-dimensional region of interest.	From study completion to 6 months after completion.
Detection rate of 68Ga-NODAGA-LM3 on per-patient basis	Percentage of patients with lesions detected on 68Ga-NODAGA-LM3 PET/CT.	From study completion to 6 months after completion.
SUVmax of lesions detected on 68Ga-NODAGA-LM3 PET/CT	The tracer uptake is quantified using maximal standard uptake value (SUVmax) by drawing a 3-dimensional region of interest.	From study completion to 6 months after completion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SUVmax of normal organs	The biodistribution of Al18F-NOTA-LM3 will be evaluated in the following organs: pituitary gland, parotids, thyroids, lungs, blood pool, liver, spleen, pancreas (head and uncinate process), gallbladder, stomach, small intestine, kidneys, and adrenal glands. SUVmax of these organs were measured and recorded.	From study completion to 6 months after completion.
Absorbed dose of target organs	Absorbed dose of target organs were calculated using HERMES software.	From study completion to 6 months after completion.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Meixi Liu, MD, Peking Uion Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Estimated): March 23, 2024
• Study Completion (Estimated): March 23, 2025

Study Registration Dates

• First Submitted: March 19, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors
• Other Study ID Numbers: ALFLM3NET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No