Abstract
Photofrin II (dihaematoporphyrin ether/ester, DHE) was labelled with indium-111 and its biodistribution in tumour bearing mice compared with that of 111In chloride. The uptake and clearance of 111In labelled DHE differed markedly from that of indium-111 chloride in that the former was not taken up by the tissues as much as the latter. Scintillation scanning with a gamma-camera showed marked uptake of both 111In agents at the site of the tumour, but a much lower tissue background (excluding the abdominal organs) for the mice given 111In DHE. Tumour:muscle ratios of dissected tissues were 2-3 times higher in 111In DHE treated animals as compared to the uptake of 111In chloride. There was a distinct difference in the pattern of distribution of the two 111In preparations in the tissues. The major accumulation of 111In chloride was in the kidneys, whereas the highest uptake of 111In DHE was in the liver, the organ in which unlabelled porphyrins accumulate. Extraction and testing of materials from tumours of 111In DHE treated animals indicated that most of the tumour extractable 111In had remained associated with the porphyrin in vivo up to 4 days after injection.
Highlights
The tumours seemed to take up relatively less of the radiolabelled DHE, compared to "'In given as the chloride, the tumour:muscle ratios found by ROI analyses of imaging data were very similar for both "'In preparations
These in vivo results are in contrast to the tissue dissection analyses, in which tumour:muscle ratios were significantly elevated for "'In DHE
The use of porphyrins in cancer diagnosis and therapy is based both on their phototoxic properties (Raab, 1900; Haussman, 1911) and on the localisation of fluorescent porphyrins in neoplastic tissues (Policard, 1924; Auler & Banzer, 1942; Figge et al, 1948)
Summary
Dihaematoporphyrin ether (DHE, Photofrin II) was obtained from Quadralogic Technologies Inc. at a concentration of 2.5mgml1' in normal saline. Carrier-free indium-111 chloride in 0.05M HCI was obtained from Merck Frosst Canada Inc. (prepared by Atomic Energy of Canada Ltd) at a specific activity of 74-333 MBq (2-9 mCi) ml-I and concentration of 9.3-42.0 ng ml-'. The binding of indium-1Il to DHE was carried out by an Experimental model. DBA/2J mice (Jackson Laboratories, Bar Harbor, MA, USA) weighing about 20g were injected in the right thigh with MI rhabdomyosarcoma cells (20,000 cells per mouse). After about 2 weeks, the tumours were approximately 1 cm in diameter and usually were not haemorrhagic or necrotic on direct examination. Tumours which were larger than 1.5cm diameter often did appear necrotic and haemorrhagic and did not label well with the "'In DHE
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