Non-invasive monitoring of photodynamic therapy with 99mTechnetium HMPAO scintigraphy

Non-invasive monitoring of photodynamic therapy with 99mTechnetium HMPAO scintigraphy

1992 | R.B. Moore, J.D. Chapman, A.D. Mokranowski, M.R. Arnfield, M.S. McPhee, A.J. McEwan
This study investigates the use of technetium HMPAO scintigraphy to monitor photodynamic therapy (PDT) in Dunning prostatic tumours. The radiopharmaceutical 99mTc-HMPAO was used to assess tumour perfusion before and after PDT. Tumours in the left flanks of rats were treated with interstitial PDT when their volumes reached 2–3 cm³. Qualitative and quantitative data from pre- and post-PDT scintigraphy showed a light-dose-dependent shutdown of tumour perfusion, which was also time-dependent. Maximal shutdown occurred about 8 hours post-PDT following a 1,600 J light dose. Light exposure 2 hours after photosensitiser administration produced a greater vascular shutdown than exposure 24 hours after. Regional differences in perfusion within treated and non-treated tumours were measured using tomographic procedures. Light-dose-dependent volumes of perfusion shutdown were demonstrated, along with naturally occurring regional differences in tumour perfusion. This radiopharmaceutical may have future utility for monitoring clinical PDT treatment of solid tumours. PDT can kill cells through direct and indirect mechanisms. Direct killing involves damage to cell membranes and organelles, while indirect killing results from microvascular damage causing cessation of blood flow and secondary tumour cell death. Previous studies showed that PDT can be enhanced by misonidazole, a bioreductive cytotoxic agent. This study used 99mTc-HMPAO scintigraphy to investigate PDT-induced vascular shutdown in both well-perfused and poorly-perfused Dunning prostate tumours. 99mTc-HMPAO is a good marker of tumour perfusion and was used to assess blood flow in human lung tumours. This non-invasive technique may be useful in the clinic for estimating the extent and kinetics of perfusion shutdown, which is important for monitoring early treatment response and scheduling adjuvant bioreductive chemotherapy. The study used a Dunning prostatic tumour model, with two sublines, R3327-H (well differentiated) and R3327-AT (anaplastic). Tumours were implanted into the left flanks of rats and treated with PDT when their volumes reached 2–3 cm³. The photosensitiser Photofrin II was administered 2 hours prior to PDT. Interstitial phototherapy was carried out using a laser tuned to 630 nm with a maximum output of 4 Watts. Tumour temperature was monitored to prevent hyperthermic effects. Scintigraphy was performed using 99mTc-HMPAO, with images obtained both supine and prone on a gamma-camera. Tomography was used to measure regional differences in perfusion. Isodose plots were used to determine light dosimetry in tumour studies. The study found that PDT-induced vascular shutdown was light-dThis study investigates the use of technetium HMPAO scintigraphy to monitor photodynamic therapy (PDT) in Dunning prostatic tumours. The radiopharmaceutical 99mTc-HMPAO was used to assess tumour perfusion before and after PDT. Tumours in the left flanks of rats were treated with interstitial PDT when their volumes reached 2–3 cm³. Qualitative and quantitative data from pre- and post-PDT scintigraphy showed a light-dose-dependent shutdown of tumour perfusion, which was also time-dependent. Maximal shutdown occurred about 8 hours post-PDT following a 1,600 J light dose. Light exposure 2 hours after photosensitiser administration produced a greater vascular shutdown than exposure 24 hours after. Regional differences in perfusion within treated and non-treated tumours were measured using tomographic procedures. Light-dose-dependent volumes of perfusion shutdown were demonstrated, along with naturally occurring regional differences in tumour perfusion. This radiopharmaceutical may have future utility for monitoring clinical PDT treatment of solid tumours. PDT can kill cells through direct and indirect mechanisms. Direct killing involves damage to cell membranes and organelles, while indirect killing results from microvascular damage causing cessation of blood flow and secondary tumour cell death. Previous studies showed that PDT can be enhanced by misonidazole, a bioreductive cytotoxic agent. This study used 99mTc-HMPAO scintigraphy to investigate PDT-induced vascular shutdown in both well-perfused and poorly-perfused Dunning prostate tumours. 99mTc-HMPAO is a good marker of tumour perfusion and was used to assess blood flow in human lung tumours. This non-invasive technique may be useful in the clinic for estimating the extent and kinetics of perfusion shutdown, which is important for monitoring early treatment response and scheduling adjuvant bioreductive chemotherapy. The study used a Dunning prostatic tumour model, with two sublines, R3327-H (well differentiated) and R3327-AT (anaplastic). Tumours were implanted into the left flanks of rats and treated with PDT when their volumes reached 2–3 cm³. The photosensitiser Photofrin II was administered 2 hours prior to PDT. Interstitial phototherapy was carried out using a laser tuned to 630 nm with a maximum output of 4 Watts. Tumour temperature was monitored to prevent hyperthermic effects. Scintigraphy was performed using 99mTc-HMPAO, with images obtained both supine and prone on a gamma-camera. Tomography was used to measure regional differences in perfusion. Isodose plots were used to determine light dosimetry in tumour studies. The study found that PDT-induced vascular shutdown was light-d
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