The effect of neoadjuvant androgen deprivation therapy on tumour hypoxia in high-grade prostate cancer: a 18F-MISO PET/MRI imaging study.

Publication date: Available online 8 March 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ismini C. Mainta, Thomas Zilli, Jean-Christophe Tille, Thomas De Perrot, Jean-Paul Vallée, Franz Buchegger, Valentina Garibotto, Raymond Miralbell
PurposeTumour hypoxia is associated with radio-resistance and poor prognosis after radiotherapy (RT) for prostate cancer (PCa). In this prospective pilot study we assessed the ability of 18F-misonidazole (18F-MISO) PET/MRI to detect hypoxia in high-grade PCa patients candidates for curative RT and we evaluated 18F-MISO PET/MRI modulation after 3 months of neoadjuvant androgen-deprivation therapy (nADT).MethodsEleven PCa patients with Gleason score (GS) ≥8 underwent 18F-Choline (18F-FCH) PET/CT at diagnosis and two 18F-MISO hybrid PET/MRI before and after 3 months of nADT, respectively. Immunohistochemistry (IHC) for tissue hypoxia and proliferation-related biomarkers (Glut1, CA-IX, VEGF-A, Ki67, HIF-1-alpha, EGFR) was performed in lesions bearing the highest GS. We used non-parametric tests to assess: 1. the presence of 18F-MISO positive regions (Tumour-to-Background ratios - TBR ≥ 1.4) at baseline; 2. The correlation between imaging parameters (PET tracers uptake, Prostate Imaging Reporting and Data System (PIRADS) scores, dynamic contrast enhancement perfusion markers) at baseline; 3. The difference in IHC staining between 18F-MISO positive and 18F-MISO negative lesions; 4. The changes in 18F-MISO PET/MRI imaging after nADT.Results18F-MISO uptake was significant in 7 patients, 5 of them being coincidental with the highest GS region. A significant correlation was found at baseline between GS and 18F-MISO TBR, between 18F-MISO TBR and MRI perfusion markers, between GS and 18F-FCH SUVmax, between GS and PIRADS and between 18F-FCH SUVmax and PIRADS. No difference was found between 18F-MISO positive and negative biopsies with respect to tissue biomarkers. 18F-MISO TBR diminished significantly after nADT only in high-grade lesions and in regions with a significant uptake at baseline.Conclusions18F-MISO PET imaging showed variable uptake in PCa, associated with a higher GS, lowering significantly after 3 months of nADT in high grade lesions. These results suggest the existence of a hypoxic microenvironment in PCa and a re-oxygenation effect of nADT.

Teaser

Tumour hypoxia is associated to treatment resistance. In this prospective study of 11 patients, we evaluated the occurrence of hypoxia in high-grade prostate cancer by multiparametric integrated18F-MISO PET/MRI before and after 3 months of androgen deprivation. Our results show the presence of hypoxic conditions in prostate carcinoma, correlated with tumour grade and responding to androgen ablation, thus supporting the re-oxygenation role of a neoadjuvant androgen deprivation therapy phase in combination with curative radiotherapy.


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