(18)F-Alfatide II PET/CT in healthy human volunteers and patients with brain metastases

Abstract

Purpose: We report the biodistribution and radiation dosimetry of an integrin αvβ3 specific PET tracer (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) (denoted as (18)F-Alfatide II). We also assessed the value of (18)F-Alfatide II in patients with brain metastases.

Methods: A series of torso (from the skull to the thigh) static images were acquired in five healthy volunteers (3 M, 2 F) at 5, 10, 15, 30, 45, and 60 min after injection of (18)F-Alfatide II (257 ± 48 MBq). Regions of interest (ROIs) were drawn manually, and the time-activity curves (TACs) were obtained for major organs. Nine patients with brain metastases were examined by static PET imaging with (18)F-FDG (5.55 MBq/kg) and (18)F-Alfatide II.

Results: Injection of (18)F-Alfatide II was well tolerated in all healthy volunteers, with no serious tracer-related adverse events found. (18)F-Alfatide II showed rapid clearance from the blood pool and kidneys. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0277 ± 0.003 mSv/MBq and 0.0198 ± 0.002 mSv/MBq, respectively. The organs with the highest absorbed dose were the kidneys and the spleen. Nine patients with 20 brain metastatic lesions identified by MRI and/or CT were enrolled in this study. All 20 brain lesions were visualized by (18)F-Alfatide II PET, while only ten lesions were visualized by (18)F-FDG, and 13 by CT.

Conclusion: F-Alfatide II is a safe PET tracer with a favorable dosimetry profile. The observed ED suggests that (18)F-Alfatide II is feasible for human studies. (18)F-Alfatide II has potential value in finding brain metastases of different cancers as a biomarker of angiogenesis.

Keywords: Alfatide II; Brain metastasis; Integrin; PET/CT; RGD peptide.

Conflict of interest statement

Conflicts of interest

None.

Figures

Figure 1

Schematic structure of 18F-NOTA-E[PEG4-c(RGDfk)]2 (denoted as [18F]Alfatide II).

Figure 2

Representative torso maximum intensity projection (MIP) images of a healthy volunteer at different time points after intravenous injection of 18F-Alfatide II. Main regions with prominent 18F-Alfatide II uptake are kidneys, spleen, liver, urinary ducts and bladder.

Figure 3

Decay corrected-time activity curves of major organs between 5 and 60 min after injection of 18F-Alfatide II in healthy volunteers (n = 5, 3 M and 2 F).

Figure 4

18F-Alfatide II (A) and 18F-FDG (B) CT, PET and corresponding PET/CT image of a lung cancer patient with left frontal lobe metastasis (patient 1 in Table 1). In the left frontal lobe metastatic lesion, 18F-Alfatide II shows a high tumor/background ratio of 9.45, but not 18F-FDG. (C) T1-, T2- and enhanced T1-weighted magnetic resonance (MR) images of the left frontal lobe metastasis. Arrows point to brain metastatic lesion.

Figure 5

18F-Alfatide II (A) and 18F-FDG (B) CT, PET and corresponding PET/CT images of a patient with unknown primary cancer and right parietal lobe metastasis (patient 9 in Table 1). CT image shows normal density compared with the contralateral lobe. In the brain metastatic region 18F-Alfatide II shows a high tumor/background ratio of 22.8, but no tumor contrast is identified with 18F-FDG PET.

Figure 6

18F-FDG (A) and 18F-Alfatide II (B) CT, PET and corresponding PET/CT images of a left lung cancer patient with right temporal lobe metastasis (patient 6 in Table 1). CT image shows high density with peripheral edema. The right temporal metastasis shows intense 18F-Alfatide II uptake with a tumor/background ratio of 13 and 18F-FDG PET shows no increased uptake.