Feasibility of imaging photodynamic injury to tumours by high-resolution positron emission tomography

Abstract

One early effect of the treatment of tumours by the new modality photodynamic therapy (PDT) is a reduction in tumour glucose levels. We have employed the widely used positron-emitting glucose analogue flurorine-18 fluoro-2-deoxy-D-glucose ([18F]-FDG), to determine whether, in principle, PDT-induced injury might be delineated non-invasively and quantitatively by positron emission tomography (PET). The scanner was of the high-density avalanche-chamber (HIDAC) type with a resolution of 2.6 mm. Subcutaneous T50/80 mouse mammary tumours, sensitised by haematoporphyrin ester, were illuminated by graded doses of interstitial 630 nm light. Thirty hours later, any remaining viable tumour was detected (a) by region-of-interest analysis of the PET images and (b) by gamma counting the excised tumour. PET measurements of % uptake of [18F]-FDG into tumour correlated closely with ex vivo gamma counting (slope=0.976, r2=0. 995), validating the in situ method. Uptake into untreated, control tumours was 3.8%+/-1.1% of the injected activity. Uptake of [18F]-FDG into treated tumours decreased by 0.7% for every 100 mm3 reduction in remaining viable histological volume. Outcome was further compared with that measured by (a) T2-weighted proton imaging on a 4.7-T magnetic resonance imaging (MRI) system and (b) histological analysis of subsequently sectioned tumours. PET using [18F]-FDG described the absolute volume of surviving tumour histological mass to the same degree as high-resolution MRI. The conclusion of these initial studies is that PET with [18F]-FDG, although non-specific, quantitatively described at early times the extent of tumour destruction by PDT.

Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization

“…Imaging techniques that have been successfully demonstrated and often clinically implemented for PDT outcome assessment include computed tomography (CT), positron emission tomography (PET),190 angiography, MRI, fluorescence imaging, and optical coherence tomography (OCT).…”

“…In 1998, Moore et al190 used flurorine-18 fluoro-2-deoxy-D-glucose to demonstrate that PET can be used to follow both tumor volume and surviving fractions at short time periods with the same degree of accuracy as high-resolution MRI. Necrosis and surviving tumor volume have also been successfully followed with pre-PDT and post-PDT contrast CT in the pancreas,171 bladder,172,173 lung, and bronchial tube.…”

Registration of micro-PET and high-resolution MR images of mice for monitoring photodynamic therapy

“…Positron emission tomography (PET) is widely used to study the physiology of many types of cancer. 3,4 Since tissue uptake of 18 F-fluorodeoxyglucose (FDG) depends on both blood flow and hexokinase activity, it can be a good probe to investigate the mechanisms of PDT that dependent on the two parameters. However, because FDG uptake depends on both, it is difficult to differentiate on the basis of FDG alone.…”

Photodynamic therapy for peripheral lung cancer

“…Unfortunately, CR cannot be confirmed solely on the basis of CT findings. It has been reported that with PET, qualitative changes in photodynamic effect can be shown and this may be used in determining results more accurately [21].…”