ISSN:
1573-7373
Keywords:
brain neoplasm
;
hematoporphyrin derivative (HpDI)
;
laser
;
malignant glioma
;
photofrin II (HpDII)
;
photoradiation therapy (PRT)
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Increasing interest has developed in the use of the photodynamic agent, Hematoporphyrin derivative (HpD) for photoradiation therapy (PRT) as adjunctive therapy of malignant glial tumors of the brain. HpD, injected systemically, is preferentially taken up and retained by neoplastic tissue. Early studies of such uptake have largely relied on gross fluorescence as evidence of tissue uptake. In this study HpD was labelled with a tritiated radioisotope (3H) in order to quantify tissue uptake in visceral and in normal and neoplastic brain tissues in a rat brain model. 3H-HpD was injected intravenously at a 10 mg/kg dose into 30 Sprague-Dawley rats (Group A) without tumors in order to clarify method. Separately, 3H-HpD of like dosage was injected into 20 Fischer-344 rats (Group B), 5 control and 15 with a 9L gliosarcoma implanted in the left anterior cerebral cortex. Post injection sacrifice occurred at 6, 24 and 48 hours. From the Sprague-Dawley group multiple somatic and cerebral specimens were assayed. Differential areas within the brain showed no significant difference in uptake. The tumor area, peritumoral margin, and distant uninvolved areas of the Fischer-344 9L rats were likewise assayed. Definite uptake of normal visceral and cerebral tissue occurred with a markedly higher uptake differential in tumor areas. Such differential was relatively consistent from trial to trial, but multiple separate values obtained in the respective study groups were often unreliabe in their reproducibility and at variance with previously reported tissue level studies. These findings implied an instability of 3H-HpDI, subsequently confirmed chromatographically as contamination probably due to time related degradation and exchange. Therefore, 3H-HpD appears to inherently carry such a risk for contamination. The compound Photofrin II (HpDII) represents a chromatographic fraction of HpD (HpDI), currently considered its most photodynamically active and purest component. Tritiated Photofrin II was used for quantification. An assay was performed with 5 Fischer-344 9L brain tumor rats (Group C), sacrificed at 24 hours. Photofrin II provided results more reliably reproducible. Contamination, degradation, and exchange of 3H-Photofrin II did not appear to occur. Neoplastic brain levels of the Photofrin II isotope were higher than in the HpD studies, and highly fluorescent. Normal brain values were consistently minimal and without fluorescence. The differential tumor/ brain ratio in Photofrin II was consequently much higher. The isolated active substrate of HpDI and HpDII(Photofrin II) appears to be the compound DiHematoporphyrin Ether (DHE). Photofrin II is comprised of some 90% DHE, while HpD is only some 50% of such. Thus Photofrin II is a notably purer and more active compound. 3H-HpD appears to be a potentially unstable compound, as perhaps are all isotopically labelled porphyrins over a given period of time. However, the suspected active component of HpD, Photofrin II, though in an early stage of evaluation may well prove to be the definitive isotopic agent of choice for quantitative experimental studies. The pure unlabelled form of Photofrin II may well prove to be the definitive agent of choice for clinical use in photoradiation therapy (PRT).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00178119
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