Monitoring response to antiangiogenic therapy of non-small cell lung cancer using ¹⁵O-water and PET

Objectives Bevacizumab (BEV), which targets tumor angiogenesis, is used in non-small cell lung cancer (NSCLC). PET using H₂¹⁵O can quantitatively evaluate antiangiogenic therapy effects by measuring tumor perfusion. The purpose of the present study is to evaluate the applicability of noninvasive image derived input function (IDIF) and to assess the therapy effect of BEV in NSCLC using IDIF.

Methods Four NSCLC patients underwent a 10 min dynamic H₂¹⁵O (185 MBq) PET scan followed by a low dose CT before administration of BEV. Data were acquired on a SET 3000 G/X scanner (Shimadzu) and reconstructed into 22 frames. During the scan, arterial blood was withdrawn continuously. Input functions were derived both from blood sampler data (BSIF) and from an ascending aorta volume of interest (IDIF). Parametric perfusion images were computed using a basis function implementation of the standard single-tissue-compartment model, together with IDIF and with BSIF. Three of four patients underwent dynamic H₂¹⁵O PET scans after administration of BEV. The times from the administration of BEV to scans were 1-2 days, 17 days and 38 days. IDIF was used to obtain perfusion images at the second, third and fourth scans.

Results Significant correlation between tumor perfusion values derived from BSIF and IDIF was found (r² = 0.89-0.98). The perfusion values averaged over tumor volume at baseline were 0.15-0.38 ml/ml/min, which were consisted with reported values. The perfusion was decreased by 6-77% at 1-2 days, by 34-72% at 17 days and by 60% at 38 days. In one case, the tumor perfusion decreased by 77% within 2 days in spite of little change in tumor size.

Conclusions IDIF is applicable for serial measurements of tumor perfusion. Monitoring tumor perfusion using H₂¹⁵O PET is promising to early evaluation of tumor response to antiangiogenic therapy.