[(68)Ga]NODAGA-RGD - Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis

Abstract

Purpose: This study was designed to determine safety, tolerability, and radiation burden of a [(68)Ga]NODAGA-RGD-PET for imaging integrin αvβ3 expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled.

Methods: After injection of 154-184 MBq [(68)Ga]NODAGA-RGD three consecutive PET/CT scans were acquired starting 8.3 ± 2.1, 36.9 ± 2.8, and 75.1 ± 3.4 min after tracer injection. For metabolite analysis, blood and urine samples were analyzed by HPLC. For dosimetry studies, residence time VOIs were placed in the corresponding organs. The OLINDA/EXM program was used to estimate the absorbed radiation dose.

Results: The radiopharmaceutical was well tolerated and no drug-related adverse effects were observed. No metabolites could be detected in blood (30 and 60 min p.i.) and urine (60 min p.i.). [(68)Ga]NODAGA-RGD showed rapid and predominantly renal elimination. Background radioactivity in blood, intestine, lung, and muscle tissue was low (%ID/l 60 min p.i. was 0.56 ± 0.43, 0.54 ± 0.39, 0.22 ± 0.05, and 0.16 ± 0.8, respectively). The calculated effective dose was 21.5 ± 5.4 μSv/MBq, and the highest absorbed radiation dose was found for the urinary bladder wall (0.26 ± 0.09 mSv/MBq). No increased uptake of the tracer was found in HCC compared with the background liver tissue.

Conclusions: [(68)Ga]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [(68)Ga]NODAGA-RGD was well tolerated and metabolically stable. Due to rapid renal excretion, background radioactivity was low in most of the body, resulting in low radiation burden and indicating the potential of [(68)Ga]NODAGA-RGD PET for non-invasive determination of integrin αvβ3 expression.

Keywords: Dosimetry; Hepatocellular carcinoma; Metabolic stability; PET; Whole-body distribution; [68Ga]NODAGA-RGD.

Fig. 1

Metabolite analysis via HPLC. Left Analysis of the blood via fractionation and subsequent measurement of the fractions in a gamma counter. Right Analysis of the urine directly with the radiodetector of the HPLC system

Fig. 2

Maximum intensity projections from static [⁶⁸Ga]NODAGA-RGD PET scans of a male patient (no. 3) with HCC starting at 13 min (a), 40 min (b), and 76 min (c) after tracer injection. The tracer shows rapid predominant renal elimination with highest radioactivity in bladder, kidneys, liver, spleen, and intestine. Low background radioactivity is found in brain, thorax, and extremities. For all three images, gray scale is set to the same values

Fig. 3

Biodistribution data of [⁶⁸Ga]NODAGA-RGD from major organs and tissue. Mean percentage injected radioactivity per liter is given (%ID/l). Data are extracted from the three static PET scans corrected for decay. White bar = 8 ± 2 min p.i.; black bar = 37 ± 3 min p.i.; gray bar = 75 ± 4 min p.i. Due to the great differences of the determined values, three different y-axes are included

Fig. 4

Organ time–activity curves and corresponding effective half-lives for [⁶⁸Ga]NODAGA-RGD averaged over all patients. The graphs present the percentage of total injected radioactivity in each organ/tissue vs. time after tracer injection. Additionally, the averaged TAC of the lesions with deficit uptake including two patients was presented (top right). Uptake/elimination of the other lesions (altogether seven patients) followed the TAC of the liver (top left)

Fig. 5

Transaxial PET/CT images of the tumor region. a Patient 7: Tracer uptake in the tumor is comparable with background radioactivity of the liver. b Patient 4: A deficit uptake is found in the lesion compared to the background radioactivity of the liver. Arrows indicate the position of the lesions