Amin I. Kassis

Biological studies of a new class of technetium complexes: the hexakis(alkylisonitrile)technetium(I) cations

This study describes the preparation and synthesis of a new class of cationic technetium compounds, the hexakis(alkylisonitrile)technetium(+ 1) complexes, at both carrier added and no carrier added concentrations in aqueous media from pertechnetate. Biological distribution and imaging data in animals indicate that certain members of this class may be effective for cardiac imaging in man. The usefulness of these lipophilic water-soluble species for labeling mammalian cells is also reported.

Bystander effect produced by radiolabeled tumor cells in vivo

The bystander effect, originating from cells irradiated in vitro, describes the biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in vitro tissue culture models and determine whether a bystander effect that is initiated by the in vivo decay of a radionuclide can be demonstrated in an animal, the ability of 5-[125I]iodo-2′-deoxyuridine (125IUdR)-labeled tumor cells to exert a damaging effect on neighboring unlabeled tumor cells growing s.c. in nude mice has been investigated. When mice are injected with a mixture of human colon LS174T adenocarcinoma cells and LS174T cells prelabeled with lethal doses of DNA-incorporated 125I, a distinct inhibitory effect on the growth of s.c. tumor (derived from unlabeled cells) is observed. Because (i) the 125I present within the cells is DNA-bound, (ii) ≈99% of the electrons emitted by the decaying 125I atoms have a subcellular range (<0.5 μm), and (iii) the overall radiation dose deposited by radiolabeled cells in the unlabeled cells within the growing tumor is <10 cGy, we conclude that the results obtained are a consequence of a bystander effect that is generated in vivo by factor(s) present within and/or released from the 125IUdR-labeled cells. These in vivo findings significantly impact the current dogma for assessing the therapeutic potential of internally administered radionuclides. They also call for reevaluation of the approaches currently used for estimating the risks to individuals and populations inadvertently exposed internally to radioactivity as well as to patients undergoing routine diagnostic nuclear medical procedures.

Kinetics of Uptake, Retention, and Radiotoxicity of 125IUdR in Mammalian Cells: Implications of Localized Energy Deposition by Auger Processes

The kinetics of uptake, retention, and radiotoxicity of 125IUdR have been studied in proliferating mammalian cells in culture. The radioactivity incorporated into the DNA is directly proportional to the duration of incubation and to the extracellular concentration of 125I. The rate of proliferation of cells is related to the intracellular radioactive concentration and is markedly reduced at medium concentrations greater than or equal to 0.1 mu Ci/ml. At 37% survival the high LET type cell survival curve is characterized by an uptake of 0.035 pCi/cell, and the cumulated mean lethal dose to the cell nucleus is about 80 rad compared to 580 rad of X-ray dose for this cell line. The strong cytocidal effects of the decay of 125I correlate with localized irradiation of the DNA by the low energy Auger electrons.

The Amazing World of Auger Electrons

Over the past 40 years, a small and highly committed group of scientists has pursued various investigations focused on understanding the physical phenomena underlying the emission of Auger electrons, the dosimetric implications of their submicroscopic deposition of energy, their radiobiological effects at the molecular and cellular levels, and their therapeutic potential in tumor‐bearing animals and patients with cancer. Herein, I present an overview ‐ historic vignette ‐ of the exciting findings reported in this field and outline the unique opportunities given to the fortunate few who have, mostly through serendipity, been working within the fascinating world of Auger electron emitters.

Radiotoxicity of 125I in mammalian cells.

The radiotoxicity of 125I in Chinese hamster V79 lung fibroblasts has been studied following extracellular (Na125I), cytoplasmic [125I]iododihydrorhodamine (125I-DR), and nuclear (125IUdR) localization of the radionuclide. Exposure of the cells for 18 h to Na125I (less than or equal to 7.4 MBq/ml) had no effect on survival. A similar exposure to 125I-DR produced a survival curve with a distinct shoulder and with a mean lethal dose (D37) of 4.62 Gy to the nucleus. While this value compares well with the 5.80 Gy X-ray D37 dose, it is in contrast to the survival curve obtained with DNA-bound 125IUdR which is of the high LET type and has a D37 of 0.80 Gy to the nucleus. Furthermore, when the uptake of 125I into DNA is reduced by the addition of nonradioactive IUdR or TdR to the medium and the survival fraction is determined as a function of 125I contained in the DNA, a corresponding increase in survival is observed. This work demonstrates the relative inefficiency of the Auger electron emitter 125I when located in the cytoplasm or outside the cell. It indicates that a high dose deposited within the cytoplasm contributes minimally to radiation-induced cell death and that radiotoxicity depends not upon the specific activity of IUdR but upon the absolute amount of 125I that is associated with nuclear DNA.

Lethality of Auger Electrons from the Decay of Bromine-77 in the DNA of Mammalian Cells

The uptake and radiotoxicity of bromine-77-deoxyuridine have been studied in V79 cells. Incorporation of

Therapeutic Radionuclides: Biophysical and Radiobiologic Principles

{}^{77}{\rm BrUdR}

Radiotoxicity of 5-[123I]iodo-2'-deoxyuridine in V79 cells: a comparison with 5-[125I]iodo-2'-deoxyuridine

into DNA of dividing cells is dependent on its extracellular concentration. The cell survival curve has no detectable shoulder and a

Radiotoxicity of an 125I-labeled DNA intercalator in mammalian cells.

D_{37}

The role of complement in hydatid disease: in vitro studies.

value of 0.13 pCi/cell. Theoretical estimates indicate that the observed high-LET-type radiotoxicity of this Auger electron emitter may be attributed to deposition of about 100 eV in a 10-A sphere around the