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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Diagnostic Test: Al18F-NOTA-LM3
* Diagnostic Test: 68Ga-DOTATATE
* Diagnostic Test: Al18F-NOTA-LM3
* Diagnostic Test: 68Ga-NODAGA-LM3


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Al18F-NOTA-LM3 and 68Ga-DOTATATE group<br>Patients will perform an Al18F-NOTA-LM3 PET/CT as well as a 68Ga-DOTATATE PET/CT. | Diagnostic Test: Al18F-NOTA-LM3<br>* 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.<br>Diagnostic Test: 68Ga-DOTATATE<br>* 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.<br>|
| Experimental: Arm B: Al18F-NOTA-LM3 and 68Ga-NODAGA-LM3 group<br>Patients will perform an Al18F-NOTA-LM3 PET/CT as well as a 68Ga-NODAGA-LM3 PET/CT. | Diagnostic Test: Al18F-NOTA-LM3<br>* 40 patients will be enrolled in this arm. All patients will undergo a whole-body PET/CT scan 60-120 minutes after injection.<br>Diagnostic Test: 68Ga-NODAGA-LM3<br>* 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.<br>|

What is the study measuring?
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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. |