The α-emitting radionuclide 211 At possesses many of the desired nuclear, chemical and radiobiological properties which make it eminently suitable for cancer therapy. The syntheses of high activity 211 At and high specific activity tumour-directed astatinated substrates, 6-[ 2 " At]-astato-MNDP and 4-[ 2 " At]-astato-MTB, have been outlined. The respective investigation of these compounds has been discussed within their context as possible high-LET endo-radiotherapeutic agents for thyroid, onco-phosphatase positive and melanotic neoplasms.
A. IntroductionThe development of tumour-specific anticancer agents represents an alternative and potentially attractive approach towards the management of disseminated malignant disease [1][2][3]. Unfortunately, the successful targeting of radionuclides to neoplastic cells by appropriately specific carrier molecules is limited by their general availability. However, by judicious consideration of tumour biochemistry, metabolism and immunology it may be possible to develop an appropriate molecular target substrate, so enabling an appreciable in situ radiocytotoxic effect to be achieved, with minimal damage to normal cells.Optimal endoradiotherapy would be best achieved by using radionuclides which decay by the emission of radiations of a high linear energy transfer (LET) quality, as they possess many advantages over the low-LET radiations usual in radiotherapy [4], The relative biological effect (RBE) of ionizing radiations has been observed to rise steadily with increasing LET reaching a maximum at approximately 100 keV μιτΓ 1 . In vitro cell studies have also demonstrated that the cell-killing effect of high-LET radiations is independent of dose-rate and as a result of its intense focal ionizing nature cell damage is lethal, being predominantly attributed to non-rejoining double strand breaks in DNA [ 5]. With such radiations there has been no evidence of repair of sub-lethal damage or potentially lethal damage [6,7]. It has also been observed that for high-LET radiations, there is a low oxygen enhancement ratio (OER) [8], so enabling comparable cytotoxic effects to be achieved in both euoxic and hypoxic tumour cell sub-populations.Astatine-211, the highest Group VIIB element, is a most suitable nuclide for therapeutic purposes. It decays along two branches: by direct α-particle decay (41.94 ± 0.50%, 5.87 MeV) to 2 glBi(f I/2 38y, decaying by electron capture to 2 g2Pb)and by electron capture to 2 84?° (tii2 0.52s) which is in transient equilibrium with 2 8sAt and subsequently decays by the emission of α-particles almost entirely of energy 7.45 MeV to form stable lead, 2 82Pb-The ranges of the α-particles of astatine-211 in unit density tissue are either, 55/Lim corresponding to energy 5.87 MeV for 42% of the disintegrations, or 80 μνη corresponding to energy 7.45 MeV for approximately 58% of the disintegrations. The total mean absorbed radiation dose in tissue is 40.7 ßGy g/Bq; the contribution from the long-lived decay of 207 Bi is negligible ( < 0.02%). The mean dose-averag...