Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [⁶⁸Ga]Ga-DOTANOC and [⁶⁸Ga]Ga-DATA^5m-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [⁶⁸Ga]Ga-DOTANOC & [⁶⁸Ga]Ga-DATA^5m-LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [⁶⁸Ga]Ga-DATA^5m-LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [⁶⁸Ga]Ga-DOTANOC PET/CT (p < 0.0001). [⁶⁸Ga]Ga-DATA^5m-LM4 had statistical significance over [⁶⁸Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p < 0.0001 (292 vs. 253 {283 lesions on CT})] and bone metastases [100% vs. 82.9%; p = 0.005 (45 vs. 34 {41 lesions on CT})]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [⁶⁸Ga]Ga-DATA^5m-LM4 showed better sensitivity and a higher target-to-background ratio than [⁶⁸Ga]Ga-DOTANOC PET/CT. [⁶⁸Ga]Ga-DATA^5m-LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy.

Purpose: This study aimed to assess the biodistribution and radiation dosimetry of ⁶⁸Ga-DATA^5m LM4 in patients with gastroenteropancreatic neuroendocrine tumors. Patients and Methods: Eight patients (5 females and 3 males) with various gastroenteropancreatic neuroendocrine tumors were included in the study. Each patient underwent 3 whole-body PET scans at 10, 60, and 120 minutes after receiving an IV injection of approximately 162.5 MBq of ⁶⁸Ga-DATA^5m LM4. Organs considered for dosimetric analysis included the liver, heart, spleen, kidneys, adrenal glands, and lumbar vertebrae (L2 to L4). Dosimetric calculations were performed using the OLINDA/EXM 2.2 software. Results: Physiological uptake of ⁶⁸Ga-DATA^5m LM4 was observed in the pituitary gland, spleen, liver, adrenal glands, and the urinary tract (kidneys and urinary bladder) for all patients. The kidneys received the highest absorbed doses at (4.77E-02 ± 1.49E-02 mSv/MBq). The mean effective dose was 2.61E-03 ± 5.99E-04 mSv/MBq. Conclusions: ⁶⁸Ga-DATA^5m LM4 injection is safe and is primarily excreted through urine, delivering the highest radiation dose to the kidneys.