abstract: Evaluation of 2-Deoxy-2-[18F]Fluoro-D-glucose- and 3′-Deoxy-3′-[18F]Fluorothymidine–Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer

Molecular Imaging and Biology, Online First™ 

Abstract

Purpose  

We evaluated whether 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and 3′-deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) could be used as imaging biomarkers of platinum resensitization in ovarian cancer.

Procedures  

Paired platinum-sensitive and platinum-resistant ovarian cancer cells from the same patient, PEO1 and PEO4, grown as tumor xenografts in nude mice, were assessed by PET.

Results  

The AKT inhibitor, API-2, resensitized platinum-resistant PEO4 tumors to cisplatin, leading to a markedly lower Ki67 labeling index (p ≤ 0.006, n = 6 per group). [¹⁸F]FDG-PET and [¹⁸F]FLT-PET imaging variables were lower after combination treatment compared with vehicle treatment (p ≤ 0.006, n = 6 per group). No changes were seen with either drug alone. PRAS40 phosphorylation status was a sensitive biochemical marker of pathway inhibition, whereas reductions thymidine kinase 1 expression defined the [¹⁸F]FLT response.

Conclusions  

Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [¹⁸F]FDG-PET and [¹⁸F]FLT-PET warranting further assessment. 

New drugs hope for those with 'resistant' cancers - media - Prof Hani Gabra/UK

"But now scientists at the charity Ovarian Cancer Action have discovered the reason why their cancers apparently develop this resistance. Rather than the cancers developing immunity, they found that minute traces of cancers that were always resistant to platinum therapy were there from the beginning. This discovery has helped them identify four or five different molecular "targets" that could be the focus of new drugs, said Prof Hani Gabra, director of the charity's research centre. He said: "These cancers look like they are platinum-resistant, but in fact they were there from the outset and they were never touched by the drugs." .....cont'd

Cochrane review: Interventions for preventing neuropathy caused by cisplatin and related compounds

AUTHORS' CONCLUSIONS: At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.