Pilot study of (89)Zr-bevacizumab positron emission tomography in patients with advanced non-small cell lung cancer

Abstract

Background: The aim of this pilot study was to evaluate whether the uptake of (89)Zr-bevacizumab in non-small cell lung cancer (NSCLC) tumors could be visualized and quantified. The correlation between tumor (89)Zr-bevacizumab uptake and tumor response to antitumor therapy with a bevacizumab-based regimen was explored.

Methods: Seven NSCLC patients underwent static PET scans at days 4 and 7 after injection of 36.4 ± 0.9 MBq (mean ± SD) (89)Zr-bevacizumab, prior to commencing carboplatin-paclitaxel-bevacizumab chemotherapy (CPB). Overall survival (OS) and progression-free survival (PFS) to CPB followed by bevacizumab maintenance therapy was correlated to tumor tracer uptake, quantified using peak standardized uptake values (SUVpeak).

Results: Zr-bevacizumab uptake (SUVpeak) was approximately four times higher in tumor tissues (primary tumor and metastases) than in non-tumor tissues (healthy muscle, lung, and fat) on days 4 and 7. A positive trend but no significant correlation could be found between SUVpeak and OS or PFS.

Conclusions: This pilot study shows that (89)Zr-bevacizumab PET imaging in NSCLC is feasible. Further investigation to validate this technique as a predictive biomarker for selecting patients for bevacizumab treatment is warranted.

Figure 1

Fused PET/CT images using FDG (A) and⁸⁹Zr-bevacizumab at day 4 (B) and day 7 (C). Per scan, an axial and coronal slice is shown. The color scale, indicating Becquerels per milliliter (BQML), ranges from 0 to a maximum value that corresponds with a SUV value of 6. In patient 1, a large tumor in the right lower lobe is seen. There is increased FDG uptake in the outer rims of the tumor and reduced uptake in the center of the tumor (probably due to necrosis). The ⁸⁹Zr-bevacizumab image on day 4 also shows high uptake in the outer rims of the tumor (T1) and high blood activity concentration (aorta descendens (AD) and heart chambers (H)). Low uptake is found in non-tumor tissues, such as healthy lung, fat, and muscle. The ⁸⁹Zr-bevacizumab image on day 7 shows high uptake in the outer rims of the tumor but low uptake in healthy tissues as well as low blood activity concentrations. In patient 2, the FDG scan shows increased uptake in both the primary tumor in the right upper lobe and enlarged mediastinal lymph node metastases. Interestingly, the ⁸⁹Zr-bevacizumab images only show increased uptake in the lymph node metastases (LN), while the uptake in the primary tumor (T2) on both days 4 and 7 is faint. In patient 3, the primary tumor, the mediastinal lymph node metastases, and rib metastasis all show increased FDG uptake. The ⁸⁹Zr-bevacizumab scans on days 4 and 7 show the highest uptake in the rib metastasis (M) and the primary tumor (T3), and moderate to high uptake is seen in the liver (L).

Figure 2

Comparison of⁸⁹Zr-bevacizumab SUV_peakand TBR in different tissues. The values were compared at day 4 (open bars) and day 7 (black bars). AD, aorta descendens; FT, fatty tissue; HL, healthy lung; LNM, lymph node metastasis; M, muscle; NLNM, non-lymph node metastasis; PT, primary tumor; TBR, tumor-to-blood ratio.

Figure 3

Comparison of tumor⁸⁹Zr-bevacizumab uptake (SUV_peak) on days 4 and 7. A correlation coefficient (r_s) of 1 (P < 0.001) was found.

Figure 4

Correlations between SUV_peakand clinical outcome (PFS and OS). The correlations are for day 4 (open circles) and day 7 (black squares). Correlation coefficients were not statistically significant for both PFS and OS, with r_s of 0.64 (P = 0.139) at days 4 and 7, respectively. PFS, progression-free survival; OS, overall survival.