Studies on the Thyroidal Uptake of Astatine in the Rat*†

Shellabarger, Claire J.; Godwin, John T.

doi:10.1210/jcem-14-10-1149

Cited by 26 publications

(11 citation statements)

References 11 publications

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“…It has been clearly established that At 21 l is accumulated, though in quanti ties much lower than for KI'31 (24), by the thyroid gland of rats, guinea pigs, monkeys, and man (25). In 90 min.…”

Section: Site and Mechanism Of Thyroidal Iodide Trappingmentioning

confidence: 95%

Thyroid

Michel¹

1956

Annu. Rev. Physiol.

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The functions of the thyroid gland are to elaborate, store, and secrete iodinated hormones. These hormones are carried away by certain blood pro teins and distributed among all the tissues. Their mode of action is n ot yet known, but there is no doubt, however, that the iodine contained in their molecul e is in volve d, so that a re view on the thyroid gland should include not only recent information on the biosynthesis of the hormones but also data on their utilization; that is, it should cover the general problem of iodine metabolism. With the limited space available here it is not possible to present all the progress which has been mad e in the last two years. This review will be an addition to the excellent article of

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Section: Site and Mechanism Of Thyroidal Iodide Trappingmentioning

confidence: 95%

Thyroid

Michel¹

1956

Annu. Rev. Physiol.

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“…Because astatine is directly below iodine in the periodic table, the pharmacokinetic behavior of their respective halide ions have some similarities; however, there also are important differences. The proclivity of astatide for the thyroid is higher than any other elemental ion except iodide, with thyroid: plasma ratios of ~200:1 observed for [ 211 At]astatide in the rat [31]. Accumulation of astatide in the stomach is similar to that of iodide; however, astatide exhibits up to an order of magnitude higher uptake compared with iodide in macrophagebearing organs such as spleen and lungs [32].…”

Section: [ 211 At]astatidementioning

confidence: 99%

Astatine-211-Labeled Radiotherapeutics An Emerging Approach to Targeted Alpha-Particle Radiotherapy

Zalutsky

Vaidyanathan²

2000

CPD

169

102

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Targeted radiotherapy or endoradiotherapy is an appealing approach to cancer treatment because of the potential for delivering curative doses of radiation to tumor while sparing normal tissues. Radionuclides that decay by the emission of alpha-particles such as the heavy halogen astatine-211 (211At) offer the exciting prospect of combining cell-specific molecular targets with radiation having a range in tissue of only a few cell diameters. Herein, the radiobiological advantages of alpha-particle targeted radiotherapy will be reviewed, and the rationale for using 211At for this purpose will be described. The chemistry of astatine is similar to that of iodine; however, there are important differences which make the synthesis and evaluation of 211At-labeled compounds more challenging. Perhaps the most successful approach that has been developed involves the astatodemetallation of tin, silicon or mercury precursors. Astatine-211 labeled agents that have been investigated for targeted radiotherapy include [211At]astatide, 211At- labeled particulates, 211At-labeled naphthoquinone derivatives, 211At-labeled methylene blue, 211At-labeled DNA precursors, meta-[211At]astatobenzylguanidine, 211At-labeled biotin conjugates, 211At-labeled bisphosphonates, and 211At-labeled antibodies and antibody fragments. The status of these 211At-labeled compounds will be discussed in terms of their labeling chemistry, cytotoxicity in cell culture, as well as their tissue distribution and therapeutic efficacy in animal models of human cancers. Finally, an update on the status of the first clinical trial with an 211At-labeled targeted therapeutic, 211At-labeled chimeric anti-tenascin antibody 81C6, will be provided.

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“…It concentrates in normal thyroid tissue to a high degree [9,10,13,14]; small doses of 211 At profoundly modify thyroid function in animals [15]. Like iodine, its ion-transport into thyroid cells can be blocked by anions of similar van der Waal's radius, e.g.…”

Section: B Sodium [ 211 At ]-Astatidementioning

confidence: 99%

“…CIO4 , TcOi, SCN" [10,11,15,16]. However, paradoxically, thiouracil and propylthiouracil, which both inhibit the Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 7/16/15 11:27 AM oxidation of iodide and its subsequent incorporation into tyrosine, cause an increased uptake of 211 At into thyroid tissue [14,16]. Though the in vivo metabolism of 211 At in thyroid tissue is dissimilar from that of its nearest homologue, precise intracellular biochemical mechanisms have not yet been fully elucidated; molecular considerations alone suggest a more complicated reaction pathway [3,17], Whilst the 0-emitting nuclide 131 1 is routinely used for the treatment of well differentiated papillary and follicular thyroid carcinoma [18], it has rarely been found to concentrate in undifferentiated variants to an extent sufficient to deliver a tumouricidal absorbed radiation dose.…”

Section: B Sodium [ 211 At ]-Astatidementioning

confidence: 99%

α-Particle Endoradiotherapy: Experimental Studies with ²¹¹ At^- and Tumour-Affinic ²¹¹ At- Biomolecules

Brown

Carpenter

1989

Radiochimica Acta

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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...

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Studies on the Thyroidal Uptake of Astatine in the Rat*†

Cited by 26 publications

References 11 publications

Thyroid

Thyroid

Astatine-211-Labeled Radiotherapeutics An Emerging Approach to Targeted Alpha-Particle Radiotherapy

α-Particle Endoradiotherapy: Experimental Studies with ²¹¹ At^- and Tumour-Affinic ²¹¹ At- Biomolecules

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Studies on the Thyroidal Uptake of Astatine in the Rat*†

Cited by 26 publications

References 11 publications

Thyroid

Thyroid

Astatine-211-Labeled Radiotherapeutics An Emerging Approach to Targeted Alpha-Particle Radiotherapy

α-Particle Endoradiotherapy: Experimental Studies with 211 At- and Tumour-Affinic 211 At- Biomolecules

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α-Particle Endoradiotherapy: Experimental Studies with ²¹¹ At^- and Tumour-Affinic ²¹¹ At- Biomolecules