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Melanogenesis Investigation Leading to Selective Melanoma Neutron Capture Therapy and Diagnosis
Author(s) -
Mishima Yutaka
Publication year - 1994
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.1994.tb03310.x
Subject(s) - melanin , melanoma , in vivo , neutron temperature , in vitro , chemistry , tyrosinase , cancer research , biophysics , neutron , biochemistry , biology , genetics , physics , quantum mechanics , enzyme
Basic investigation into the nature of melanin monomer and polymer synthesis in pigment cells has revealed many of the new underlying factors involved in its regulation and control by three melanogenesis‐related genes, tyrosinase, TRP‐1 and TRP‐2, and other non‐tyrosinase glycoproteins. Pigment cells can undergo clinically and biologically recognizable progressive multi‐step carcinogenesis. Generally parallel to this progressive cancerization is accentuated melanogenesis. Using this accentuated melanogenesis to develop a specific diagnosis and cure for melanoma (Mm) has long been a challenge. However, until recently, no success was achieved. As an example, attempting to utilize the fact that dopa accumulates as a melanin substrate within Mm cells, hybrid compounds of dopa and cytotoxic drugs were developed. However, these compounds were found to have severe systemic side effects and were therefore unusable. Another newer Mm treatment involves high energy radiation such as fast neutrons. But this is quite non‐selective, killing both the target cancer and the normal surrounding tissue. Since 1972, I have developed the idea of coupling the high energy releasing system of thermal neutron irradiation with the non‐toxic 10 B‐dopa analogue, 10 B 1 ‐ l ‐ p ‐boronophenylalanine ( 10 B 1 ‐ l ‐BPA). Thermal neutrons are essentially harmless, but, after specific absorption by 10 B, release high LET α‐particles and 7 Li‐atoms with an energy of 2.33 MeV up to a distance of 14 μ, the diameter of Mm cells, thus selectively killing them without damaging surrounding normal tissue. After the synthesis of 10 B 1 ‐ l ‐BPA, exhaustive in vitro and in vivo radiological studies on its enhanced killing effect were done to develop optimal Mm Boron Neutron Capture Therapy (NCT). We have successfully treated 14 Mm cases to date. Our Mm NCT can be a prototype for the treatment of many other cancers which synthesize specific proteins. Following our progress with NCT, we recently developed a powerful, novel method for accurate diagnosis and 3‐dimensional imaging of Mm using Positron Emission Tomography with new 18 F‐ 10 B‐BPA. We can also determine the 10 B concentration in target melanomas and blood essential for most effective NCT.