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P Micca

Publications and source records attributed to P Micca.

8 recordsLinked to original sources
PubMed1994

Boron neutron capture therapy: a guide to the understanding of the pathogenesis of late radiation damage to the rat spinal cord.

PURPOSE: Before the commencement of new boron neutron capture therapy (BNCT) clinical trials in Europe and North America, detailed information on normal tissue tolerance is required. In this study, the pathologic effects of BNCT on the central nervous system (CNS) have been investigated using a rat spinal cord model. METHODS AND MATERIALS: The neutron capture agent used was 10B enriched sodium mercaptoundecahydro-closododecaborate (BSH), at a dosage of 100 mg/kg body weight. Rats were irradiated on the thermal beam at the Brookhaven Medical Research Reactor. The large spine of vertebra T2 was used as the lower marker of the irradiation field. Rats were irradiated with thermal neutrons alone to a maximum physical absorbed dose of 11.4 Gy, or with thermal neutrons in combination with BSH, to maximum absorbed physical doses of 5.7 Gy to the CNS parenchyma and 33.7 Gy to the blood in the vasculature of the spinal cord. An additional group of rats was irradiated with 250 kVp X rays to a single dose of 35 Gy. Spinal cord pathology was examined between 5 and 12 months after irradiation. RESULTS: The physical dose of radiation delivered to the CNS parenchyma, using thermal neutron irradiation in the presence of BSH, was a factor of two to three lower than that delivered to the vascular endothelium, and could not account for the level of damage observed in the parenchyma. CONCLUSION: The histopathological observations of the present study support the hypothesis that the blood vessels, and the endothelial cells in particular, are the critical target population responsible for the lesions seen in the spinal cord after BNCT type irradiation and by inference, after more conventional irradiation modalities such as photons or fast neutrons.

Animals↗
PubMed1990

Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma.

The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. We have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of that observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma.

Animals↗
PubMed1989

Recent developments in neutron capture therapy.

The conditions for the possible initiation of clinical trials with neutron capture therapy at a number of locations in the U.S. is reviewed. There are several new technical developments or plans at the Brookhaven Medical Research Reactor (BMRR), the Power Burst Facility (PBF) at INEL, the Massachusetts Institute of Technology Reactor (MITR) and the Georgia Institute of Technology Research Reactor (GTRR). Emphasis is on the development of epithermal beams for the treatment of deepseated tumors with neutron fluxes in between 10(9) to 10(10) n/cm2s. Therapeutic dose gains, defined as the ratio of tumour dose to maximum normal tissue dose in the treatment volume are expected to be between 2 and 4, depending on the degree of suppression of fast neutron dose. Boron concentrations considered in this case in the tumour are around 35 micrograms 10B/g and tumour/normal tissue concentrations are around 10. The compound development throughout three generations is discussed. The compound proposed nowadays, Na2B12H11SH (or BSH), employed in the treatments in Japan, will likely be replaced in the future by analogous of biomolecules being enriched in the tumour by physiological pathways. Examples are p-boronophenylalanine or boronated porphyrius. The most promising solution envisaged would be the employment of tumour cell specific brononated monoclonal antibodies. Finally the mode of therapy is discussed which will likely be based on a fractioned scheme, to achieve optimized results.

Fast Neutrons↗
PubMed1986

Iodothiouracil as a melanoma localizing agent.

Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.

Animals↗