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. 2021 Mar 17:11:606210.
doi: 10.3389/fonc.2021.606210. eCollection 2021.

Evaluation of 18F-FMISO PET and 18F-FDG PET Scans in Assessing the Therapeutic Response of Patients With Metastatic Colorectal Cancer Treated With Anti-Angiogenic Therapy

Sze Ting Lee  1   2   3   4   5 , Niall Tebbutt  3   4   6 , Hui Kong Gan  2   3   6 , Zhanqi Liu  2 , John Sachinidis  1 , Kunthi Pathmaraj  1 , Andrew Mark Scott  1   2   3   5
Affiliations

Evaluation of 18F-FMISO PET and 18F-FDG PET Scans in Assessing the Therapeutic Response of Patients With Metastatic Colorectal Cancer Treated With Anti-Angiogenic Therapy

Sze Ting Lee et al. Front Oncol. .

Abstract

Introduction: Tumor hypoxia and angiogenesis are implicated in tumor growth and metastases, and anti-angiogenic therapies have an important role in treating patients with metastatic colorectal cancer. However, the prevalence of hypoxia has not been fully evaluated in colorectal liver metastases, and hypoxic response to anti-angiogenic therapy has not been clearly established. The aims of the study were to evaluate the changes seen on 18F-FMISO and 18F-FDG PET scans in patients treated with anti-angiogenic therapy, and to correlate these measures of hypoxia and metabolism with clinical outcomes, and blood biomarkers of angiogenesis.

Methods: Patients with metastatic colorectal carcinoma planned for treatment with bevacizumab and chemotherapy received routine staging investigations prior to any treatment, including a FDG PET scan. A FMISO PET scan was performed within 4 weeks of staging tests, with blood specimens collected at that time for serum VEGF and osteopontin measurement. Follow-up FDG and FMISO scans were performed after 1 cycle of treatment. Results were compared to response (RECIST), progression free survival (PFS), and overall survival (OS).

Results: A total of 15 patients were recruited into this prospective trial, of which 13 patients were evaluable for assessment of treatment follow-up. Baseline FDG uptake was higher than FMISO uptake, and there was a significant decrease in FDG uptake (SUVmax and TGV) but not FMISO uptake (SUVmax and TNR) after treatment. There was a positive correlation between FDG and FMISO SUVmax on both baseline and post-treatment PET scans. Blood biomarkers of serum VEGF and osteopontin were significantly correlated with the FDG and FMISO PET parameters.

Conclusions: This study shows that hypoxia in metastatic colorectal cancer, assessed by FMISO PET, shows minor changes following initial treatment with anti-angiogenic therapy, but is associated with therapeutic response. FDG PET uptake changes (SUVmax, TLG) are also associated with response to anti-angiogenic therapy. These findings demonstrate the interplay between tumor metabolism and hypoxic regulation following anti-angiogenic treatment of metastatic colorectal cancer.

Keywords: angiogenesis; bevacizumab; fluoromisonidazole (FMISO) positron emission tomography (PET); hypoxia; metastatic colorectal carcinoma; response.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Pre and post-treatment FDG and FMISO PET scans in patient 8 in transverse (top row) and coronal (bottom row) projections. This shows complete metabolic and hypoxic response in the liver metastases to treatment, with photopenic defects in the liver on post-treatment scans. (B) Pre and post-treatment FDG and FMISO PET scans in patient 12 in transverse (top row) and coronal (bottom row) projections. This shows incomplete metabolic and hypoxic response to treatment on FDG & FMISO PET in retroperitoneal lymph nodes seen on CT (white arrowhead). Intense bowel activity on FMISO scans is noted anteriorly (black arrows).
Figure 2
Figure 2
(A) Correlation between baseline FDG and FMISO SUVmax, with a Pearson’s correlation of 0.67 and p-value of 0.007. (B) Correlation between baseline FDG and FMISO TNR, with a Pearson’s correlation of 0.49 with a non-statistically significant p-value of 0.06. (C) Correlation between post-treatment FDG and FMISO SUVmax, with a Pearson’s correlation of 0.61 and p-value of 0.06. (D) Correlation between post-treatment FDG and FMISO TNR, with a Pearson’s correlation of 0.79 and p-value of 0.0014.
Figure 3
Figure 3
Waterfall plot of the changes seen of PET parameters on FDG and FMISO PET scans, and RECIST measurements on diagnostic CT for each patient.
Figure 4
Figure 4
Post-treatment FMISO TNR and PFS and OS. (A) Post-treatment FMISO TNR and PFS (p-value 0.16); (B) Post-treatment FMISO TNR and OS (p-value 0.14).
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