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J L Humm

Publications and source records attributed to J L Humm.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effective targeting of magnetic radioactive 90Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results.

Magnetic biodegradable poly(lactic acid) microspheres that incorporate both magnetite and the beta-emitter 90Y were prepared. By applying a directional external magnetic field gradient in excess of 0.02 Tesla/cm across a 96-well plate containing neuroblastoma cells incubated with the 90Y magnetite loaded microspheres, the radiation dose to the cells could be enhanced or reduced relative to the dose from a uniform loading of the well with 90Y-DTPA. Using the MTT assay, cell survival was measured for the magnetic field directed from above (cell sparing) and from below (cell targeting) the well plate, resulting in 65 +/- 8% or 18 +/- 5% survival respectively. This method was then applied to an in vivo murine tumor model. The biodistribution of intraperitoneally injected magnetic radioactive microspheres, after 24 h in mice, showed that 73 +/- 32% of the radioactivity was found on the subcutaneous tumor that had a rare earth magnet fixed above it. In contrast, the tumor radioactivity with no attached magnet was 6 +/- 4%. Magnetically targeted radiopolymers such as 90Y-microspheres show great promise for regional or intracavitary radiotherapy.

Animals↗
PubMed1995

The spatial accuracy of cellular dose estimates obtained from 3D reconstructed serial tissue autoradiographs.

In order to better predict and understand the effects of radiopharmaceuticals used for therapy, it is necessary to determine more accurately the radiation absorbed dose to cells in tissue. Using thin-section autoradiography, the spatial distribution of sources relative to the cells can be obtained from a single section with micrometre resolution. By collecting and analysing serial sections, the 3D microscopic distribution of radionuclide relative to the cellular histology, and therefore the dose rate distribution, can be established. In this paper, a method of 3D reconstruction of serial sections is proposed, and measurements are reported of (i) the accuracy and reproducibility of quantitative autoradiography and (ii) the spatial precision with which tissue features from one section can be related to adjacent sections. Uncertainties in the activity determination for the specimen result from activity losses during tissue processing (4-11%), and the variation of grain count per unit activity between batches of serial sections (6-25%). Correlation of the section activity to grain count densities showed deviations ranging from 6-34%. The spatial alignment uncertainties were assessed using nylon fibre fiduciary markers incorporated into the tissue block, and compared to those for alignment based on internal tissue landmarks. The standard deviation for the variation in nylon fibre fiduciary alignment was measured to be 41 microns cm-1, compared to 69 microns cm-1 when internal tissue histology landmarks were used. In addition, tissue shrinkage during histological processing of up to 10% was observed. The implications of these measured activity and spatial distribution uncertainties upon the estimate of cellular dose rate distribution depends upon the range of the radiation emissions. For long-range beta particles, uncertainties in both the activity and spatial distribution translate linearly to the uncertainty in dose rate of < 15%. For short-range emitters (< 100 microns), such as alpha particle sources, the magnitude of the uncertainty in serial section alignment is comparable with the particle track length. Under these circumstances, dosimetric errors are introduced in proportion to the serial section alignment inaccuracy.

Animals↗
PubMed1994

Radiobiologic studies of low-dose-rate 90Y-lymphoma therapy.

BACKGROUND: Radioimmunotherapy and other forms of biologically targeted radiopharmaceutic treatment appear to show unexpected efficacy in many patients with lymphoma, neuroblastoma, and several other types of nonepithelial malignancies. The radiobiologic mechanisms responsible for this high clinical radioresponsiveness are unclear, but must involve some sort of cytotoxic enhancement or sensitization to protracted courses of low-dose-rate radiation exposure. MATERIALS AND METHODS: A series of in vitro experiments was performed with malignant lymphoma cell lines exposed under various conditions to high-dose-rate external beam radiotherapy or low-dose-rate 90Y radiation. Data were collected on cell cycle effects, DNA fragmentation, and modulation of cytotoxicity by caffeine and treatment sequence alterations. RESULTS: The data showed that some malignant lymphoma lines are highly sensitive to low-dose-rate radiation and that a portion of the cytotoxicity appears to be mediated by the induction of radiation-associated apoptosis (programmed cell death). Cell cycle effects of low-dose-rate radiation (such as G2M block) appear to be relatively minor in this experimental system. Agents that modulate apoptosis (such as the calcium-releasing agent caffeine) significantly enhance cell kill and DNA fragmentation after 90Y treatment. CONCLUSIONS: These results suggest that radiation-associated apoptosis may be important in the radiobiology of targeted radiopharmaceutical therapy.

Animals↗
PubMed1994

A miniature MOSFET radiation dosimeter probe.

Prototype miniature dosimeter probes have been designed, built, and characterized employing a small, radiation sensitive metal oxide semiconductor field effect transistor (MOSFET) chip to measure, in vivo, the total accumulated dose and dose rate as a function of time after internal administration of long range beta particle radiolabeled antibodies and in external high energy photon and electron beams. The MOSFET detector is mounted on a long narrow alumina substrate to facilitate electrical connection. The MOSFET, alumina substrate, and lead wires are inserted into a 16 gauge flexineedle, which, in turn, may be inserted into tissue. The radiation dosimeter probe has overall dimensions of 1.6 mm diam and 3.5 cm length. The MOSFET probe signals are read, stored, and analyzed using an automated data collection and analysis system. Initially, we have characterized the probe's response to long range beta particle emission from 90Y sources in solution and to high energy photon and electron beams from linear accelerators. Since the prototype has a finite substrate thickness, the angular dependence has been studied using beta particle emission from a 90Sr source. Temperature dependence and signal drift have been characterized and may be corrected for. Measurements made in spherical volumes containing 90Y with diameters less than the maximum electron range, to simulate anticipated geometries in animal models, agree well with Berger point kernel and EGS4 Monte Carlo calculations. The results from the prototype probes lead to design requirements for detection of shorter range beta particles used in radioimmunotherapy and lower photon energies used in brachytherapy.

Biophysical Phenomena↗
PubMed1994

Dosimetry of Auger-electron-emitting radionuclides: report no. 3 of AAPM Nuclear Medicine Task Group No. 6.

The biological effects of Auger-electron-emitting radionuclides can be as severe as those of alpha particles of high linear energy transfer. A great deal of effort has been expended in exploring the biological effects of Auger electron emitters. Much of this effort has been devoted to improving theoretical and experimental techniques required to calculate absorbed doses and correlate them with the observed biological effects. Given that the main purpose of dosimetry is to obtain a physical descriptor with which to correlate radiation toxicity, then nowhere is this challenge greater than when biological specimens are subject to Auger electron cascades. The dense shower of short-range Auger electrons released by radionuclides, which decay by electron capture or internal conversion, results in biological damage that is highly dependent on the location of the decay site within the cell. In this report, different approaches to Auger electron dosimetry are described and compared. Methods to calculate the absorbed dose from Auger electron emitters at the DNA, cellular, multicellular, and organ levels are described as they relate to the biological effects. The concept of a radiation weighting factor for Auger electrons to be used in the calculation of equivalent dose is reviewed. The importance of subcellular distribution of Auger emitters in determining the biological effects of these radionuclides is emphasized and incorporated into the equivalent dose formalism. The Task Group recommends that a preliminary radiation weighting factor of 10 be used for deterministic effects of Auger electrons, and a value of 20 for stochastic effects.

Biophysical Phenomena↗
PubMed1994

Collision avoidance in computer optimized treatment planning.

Of major concern in fully automated computerized treatment delivery is the possibility of gantry/couch or gantry/patient collisions. In this work, software has been developed to detect collisions between gantry and couch or patient for both transaxial and noncoplanar treatment fields during the treatment planning process. The code uses the gantry angles, turntable angles, and position of the couch surface relative to the isocenter supplied by the planner for the prescribed radiation fields. In addition, the maximum patient anterior-posterior and lateral separations are entered in order to model the patient outline by a conservative cylindrical ellipse. By accessing a database containing the precise mechanical dimensions of the therapy equipment, 3D analytical geometry is used to test for collisions between gantry/patient and gantry/couch for each treatment field. When collisions are detected, the software inspects the use of an extended distance treatment, by recalculating and testing for collisions, with the couch at a greater distance from the collimator along the direction of the central axis. If a collision is avoided at extended distance, the lateral, longitudinal, and vertical motions of the couch are recorded for entry into the treatment plan, or else a warning message is printed, together with the nearest permissible collision-free gantry angle. Upon inspection, the planner can either elect to use the calculated closest permissible gantry angle or reject the plan. The software verifies that each proposed treatment field is safe, but also that the transition between fields is collision-free. This requires that the sequence of the treatment fields be ordered, preferably into a sequence which minimizes the delivery time compatible with patient safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Accident Prevention↗
PubMed1994

Image analysis for the study of radionuclide distribution in tissue sections.

UNLABELLED: Tissue section autoradiographs are often prepared to review the precise spatial locations of a radiolabeled molecule relative to cells, such as in the study of radiolabeled antibody distribution. The objective of this work was to develop and evaluate a method to automatically detect both grains and cell nuclei from stained tissue autoradiographs using a microscope and an image analyzer. METHOD: Using a sequence of morphological image operations, the densely stained regions of the section, representing the cell nuclei are identified first, and then subtracted from the original image. This enables the identification of autoradiographic grains under conditions of variable contrast, by separation of the grains overlapping the cell nuclei from the extracellular spaces, permitting a more accurate and robust automatic segmentation routine. RESULTS: The accuracy of the method to detect grains has been evaluated at different threshold levels. The highest accuracy obtained was approximately 90%. The accuracy in the detection of cell nuclei was histology-dependent. As examples, we have estimated accuracies of approximately: 86%, 81% and 77% for kidney, EL-4 lymphoma and pneumonocyte sections, respectively. CONCLUSION: This method was tested using specimens designed to study radiolabeled antibody distribution, but it should be applicable with comparable accuracy to other radiolabeled compounds for which quantitative information on the heterogeneity of distribution is required.

Animals↗
PubMed1993

Cell cycle alterations, apoptosis, and response to low-dose-rate radioimmunotherapy in lymphoma cells.

PURPOSE: In an attempt to elucidate some aspects of the radiobiological basis of radioimmunotherapy, we have evaluated the in vitro cellular response patterns for malignant lymphoma cell lines exposed to high- and low-dose-rate radiation administered within the physiological context of antibody cell-surface binding. METHODS AND MATERIALS: We used two different malignant lymphoma cell lines, a Thy1.2+ murine T-lymphoma line called EL-4 and a CD20+ human B-lymphoma line called Raji. Cells were grown in suspension cultures and exposed to high-dose-rate gamma radiation from an external 137Cs source or low-dose-rate beta radiation from DTPA-solubilized 90Y in solution. In some experiments, cells were pre-incubated with an excess of nonradioactive antibody in order to assess the effects of immunoglobulin surface binding during radiation exposure. Irradiated cells were evaluated for viability, cell-cycle changes, patterns of post-radiation morphologic changes, and biochemical hallmarks of radiation-associated necrosis and programmed cell death. RESULTS: The EL-4 line was sensitive to both high-dose-rate and low-dose-rate irradiation, while the Raji showed efficient cell kill only after high-dose-rate irradiation. Studies of radiation-induced cell cycle changes demonstrated that both cell lines were efficiently blocked at the G2/M interface by high-dose-rate irradiation, with the Raji cells appearing somewhat more susceptible than the EL-4 cells to low-dose-rate radiation-induced G2/M block. Electron microscopy and DNA gel electrophoresis studies showed that a significant proportion of the EL-4 cells appeared to be dying by radiation-induced programmed cell death (apoptosis) while the Raji cells appeared to be dying primarily by classical radiation-induced cellular necrosis. CONCLUSION: We propose that the unusual clinical responsiveness of some high and low grade lymphomas to modest doses of low-dose-rate radioimmunotherapy may be explained in part by the induction of apoptosis. The unusual dose-response characteristics observed in some experimental models of radiation-induced apoptosis may require a reappraisal of standard linear quadratic and alpha/beta algorithms used to predict target tissue cytoreduction after radioimmunotherapy.

Animals↗
PubMed1993

Effect of set-up error on the dose across the junction of matching cranial-spinal fields in the treatment of medulloblastoma.

PURPOSE: The effect of systematic and stochastic setup error on the dose delivered to the gap region for the three field radiation treatment of medulloblastoma is studied. The consequences of such setup error is discussed. METHODS AND MATERIALS: The treatment of medulloblastoma is typically a 3 field technique, in which two lateral cranial fields are matched with a spine field. The x-ray dose delivered to the region between the matched fields depends upon the gap size. The choice of the gap width between the cranial and spinal fields is controversial. It is currently a compromise between minimizing the risk of dose hot spots to the spine, and the associated clinical complications, as well as the magnitude of cold spots (underdosing) across the gap, with the associated risk of disease recurrence. In this paper, we examine the effect of gap width with a moving junction, referred to as "field feathering", on the dose across the field junction for a 6MV photon beam. In addition, we have studied 129 portal films and 40 simulation films to assess the accuracy and precision of patient setup during treatment with a plan involving feathered fields. Selected landmarks observable on both portal and simulation films were identified and the variation in the distances to the field edges measured. The distribution of patient setup error was convoluted with the beam profiles for a 6MV linac. These convoluted field edges were used obtain dose profiles across the gap region as a function of gap separation. The consequences for therapy are discussed. In addition, analysis of patient setup error on an alternative treatment involving beam modifiers to broaden the beam penumbra is discussed. RESULTS: The magnitude of the spatial stochastic and systematic setup error was determined to be approximately three and two millimeters respectively. The dosimetric consequences of patient setup error lead to over and under dosing in the spinal gap region for the three field technique. The degree of under or over dose depends on the nature and magnitude of the patient setup error. CONCLUSIONS: The effect of patient setup error can lead to significant dosimetric errors in the dose to the gap region depending on the magnitude of the setup errors. The effective over and under dose can be compensated by the use beams modifiers such as a beam spoiler or vibrating jaws.

Calibration↗
PubMed1993

G2M arrest and apoptosis in murine T lymphoma cells following exposure to 212Bi alpha particle irradiation.

Asynchronous exponentially growing EL4 murine T lymphoma cells were exposed either to high LET alpha-radiation from 212Bi-DTPA or to gamma-radiation from a 137Cs source. Radiation-induced cell cycle perturbation was studied by flow cytometry. Alpha irradiation, like gamma, transiently arrested cells in the G2M phase in a dose-dependent manner. The maximum percentages of cells accumulated in G2M 18 h after alpha- and gamma-irradiation were comparable, though the dose-response relationships differed. The "RBE" value for G2M block for alpha- versus gamma-radiation was approx. 4. Electron microscopic studies of the cell samples where a large proportion of cells were arrested in G2M showed subcellular changes in nuclear membrane and the presence of morphologically apoptotic cells. Biochemical analysis of DNA from irradiated cells by agarose gel electrophoresis revealed more extensive DNA fragmentation for alpha- vs gamma-irradiation, even at relatively low total doses. We conclude that the high LET radiation is more efficient in inducing G2M block and apoptosis in EL4 lymphoma cells. The overall radiosensitivity of some high and low grade malignant lymphoma cells to radiation may correlate with these processes. The clinical implications of 212Bi-induced G2M delay may be particularly important for biologically targeted high LET radiopharmaceutical therapy.

Alpha Particles↗
PubMed1993

Morphological, biochemical, and molecular changes in endothelial cells after alpha-particle irradiation.

The response of cultured bovine aortic endothelial (BAE) cells after exposure to alpha-particle radiation from chelated 212Bi has been evaluated. The results suggest that even relatively high doses of alpha-particle radiation from 212Bi (20-72 Gy) cause only minor acute changes in the morphology of BAE cells (light and electron microscopy) under conditions of confluent monolayer growth. Significant morphological changes can be detected in cells that detach from the monolayer, though it is unclear whether these changes represent a genuine response to irradiation or reflect the causes or effects of monolayer detachment with the consequent loss of intercellular biochemical communication. After alpha-particle irradiation (20-40 Gy) angiotensin-converting-enzyme activity was not detectable in the monolayer culture medium but was significantly decreased within the cell monolayer. Neutral-elution-assay data demonstrated that DNA double-strand-break (DSB) damage occurred in these cells and that about 35% of the DSBs were repairable.

Alpha Particles↗
PubMed1993

Internal dosimetry using data derived from autoradiographs.

Cancer therapies based on administered radionuclides require accurate information on tumor dose. One of the major factors influencing the distribution of absorbed-dose characteristics is the uniformity of the radiolabel distribution in tissue. To study the effect of nonuniformities, we used image analysis techniques to measure automatically the coordinates of autoradiographic grains (sources) and cell nuclei in cut sections from three different tumors, following treatment with radiolabeled antibodies. The spatial distribution data of sources and cell nuclei from these tumor sections were assessed and the pattern of energy deposition in the cell nuclei calculated, assuming that each autoradiograph grain corresponded to a source of the alpha emitter astatine-211 (211At) or the beta emitter yttrium-90 (90Y). The distribution of deposited energy obtained for the real grain distributions was compared to the distribution assuming a locally uniform source distribution, i.e., simulating grain count averaging as produced by a microdensitometric method within a 100 x 100 microns 2 frame size (frame averaging), and a uniform distribution across the entire section (section averaging). The results show first that when the grain distribution is uniform, the average dose within the section is an adequate estimate of the dose to the cell nuclei. Second, when the grain distribution is nonuniform, the distribution of doses to the cell nuclei is significantly less when calculations use the measured grain coordinates, or frame averaging, than when section averaging is used. Third, when the sources are located on or in the cells, both frame and section averaging produce underestimates of the dose to the cell nuclei.

Animals↗
PubMed1993

A model of cell inactivation by alpha-particle internal emitters.

Tumor-associated antibodies labeled with 131I and 90Y have been used in the treatment of malignant disease with some success. The use of alpha-particle-emitting radionuclides as radiolabels offers potential advantages over beta-particle sources. The short range in tissue (< 100 microns) and the high linear energy transfer associated with alpha-particle emitters will result in a more concentrated deposition of energy at the site of radionuclide decay. Thus, if radiolabeled antibodies can be bound to malignant cells specifically, a high differential cell killing can be achieved between the malignant and the normal cells. However, the energy deposition pattern will be strongly dependent upon the configuration of alpha-particle sources relative to the cells, and will consequently impact upon the dose-response characteristics. The purpose of this paper is to study distributions of energy deposition from alpha-particle-emitting radioimmunoconjugates distributed uniformly and nonuniformly around cells through theoretical modeling. Energy deposition spectra for cell nuclei are calculated and used to estimate the survival fraction by a simple biological model. We show that survival curves resulting from nonuniform distributions of alpha-particle-emitting radiolabeled antibodies can depart significantly from the classical exponential survival model applied to external alpha-particle beams. The survival curves may have initial slopes much steeper than those produced by a uniform distribution of sources, and they may also depart from linearity. Furthermore, the results of the modelling indicate how survival curves are dependent on the cell and radiolabel spacing. The results from our model compare reasonably well with published experimental data and can be used to facilitate the design and interpretation of radiobiological experiments.

Alpha Particles↗
PubMed1992

Analysis of cytotoxicity of 131I-labelled OC125 F(ab')2 on human epithelial ovarian cancer cell lines.

Monoclonal antibody (mAb) OC125 detects the cell surface-antigen CA125, which is expressed in more than 80% of epithelial ovarian cancers but not in normal adult ovaries. Its high specificity and binding affinity makes OC125 a potential candidate for use in radioimmunotherapy (RIT) in patients with recurrent ovarian cancer. Initial biodistribution studies using radiolabelled specific mAbs have demonstrated significant increase in tumor uptake of dose as compared to radiolabelled irrelevant antibody. We report here an isodose comparison of the cytotoxicity of 131I-labelled OC125 F(ab')2, 131I-labelled nonspecific protein and external beam irradiation using a cesium-137 gamma source. Enhancement of cytotoxity due to the specific binding of the mAb could only be observed when a critical activity of 131I localized at the cell membrane. At a specific activity labelling of less than 4.1 mCi/mg, the antigen specificity of OC125 does not contribute to cell kill. Using a specific activity of 10.2 mCi/mg, the relative biological effectiveness of 131I-labelled OC125 (F(ab')2 was increased by a factor of 5 compared with external-beam X-ray therapy, and the specificity of mAb OC125 was found to enhance the cytotoxicity of the radioimmunoconjugate (RIC) by a factor of 2.7. This low value is in accordance with previously reported theoretical calculations for long range, low-LET isotopes and may be one of the reasons why RIT using 131I has severe limitations. In conclusion, it is necessary to maximize the specific activity of RICs with low-LET isotopes such as iodine-131 in order to maximize the ratio of the dose delivered specifically by membrane-bound mAb versus free-floating nonspecific protein.

Adenocarcinoma↗
PubMed1992

DNA damage produced in V79 cells by DNA-incorporated iodine-123: a comparison with iodine-125.

The neutral elution technique (pH 9.6) has been used to compare the damage produced in the DNA of V79 cells following the decay of the Auger-electron emitters 123I and 125I incorporated into DNA in the form of 5-[123I/125I]iodo-2'-deoxyuridine (123IdU, 125IdU) or after 60Co gamma irradiation. Elution profiles of retained radioactivity versus eluted volume were generally found to be nonlinear and partially dependent on the cell treatment prior to elution. Plots of a suitable function of radioactivity retention on the filters versus total decays for 123I or 125I and dose (Gy) for gamma radiation were linear. Assuming that each 125I decay produces one double-strand break (DSB), the 60Co efficiency in DSB production was found to be 53.4 DSBs/Gy/cell (or 17.8 DSBs/Gy/10(12) Da), in agreement with values reported previously. The decay of 123I led to 0.74 DSB/decay/cell if decays occurring only during nonrepair conditions were counted. This DSB production efficiency is in agreement with Monte Carlo semiempirical models of the action of radiation on DNA.

Animals↗
PubMed1992

Cellular kinetics, dosimetry, and radiobiology of alpha-particle radioimmunotherapy: induction of apoptosis.

Though clinical results for radioimmunoconjugate therapy of most common epithelial tumors have been disappointing, dramatic responses have been observed repeatedly in the treatment of high- and low-grade malignant lymphomas. This high clinical responsiveness after radioimmunoconjugate therapy sometimes appears to be out of proportion to the calculated radiation dose absorbed by the lymphoma tissue. Here we describe some key aspects of the kinetics, dosimetry, and cellular radiobiology of murine lymphoma cells exposed to 212Bi-radiolabeled alpha-particle-emitting immunoconjugates specific for the differentiation antigen Thy 1.2. Approximately 25 cell-bound alpha-particle-emitting immunoconjugates per target cell were required to reduce clonogenic survival by 90% (the radiobiological D10). Serial kinetic analyses of the antibody and radioisotope components of the immunoconjugates revealed significant levels of dechelation and up to 7.5% cellular internalization of the isotope. Cellular radiation dosimetry performed by Monte Carlo computer simulation of alpha-particle energy deposition patterns based on the observed radiopharmacokinetics showed that the D10 resulted from approximately four alpha-particle traversals through the nucleus, corresponding to an absorbed radiation dose of approximately 0.95 Gy to the cell nucleus. Electron micrographs and DNA gel studies of murine lymphoma cells undergoing radioimmunoconjugate therapy in vivo and in vitro demonstrated bizarre blebbing patterns, condensation of chromosomal material, and internucleosomal DNA fragmentation patterns characteristic of programmed cell death (apoptosis). We conjecture that the efficacy of radioimmunoconjugates against responsive cell types may be the result of passive DNA damage by ionizing radiation and the initiation of apoptosis in response to radioimmunotherapy.

Alpha Particles↗
PubMed1991

Tissue dose estimates following the selective uptake of 125IUdR and other radiolabelled thymidine precursors in resistant tumours.

For the purposes of evaluation of the therapeutic potential of the radiohalogenated thymidine analogue 125IUdR, estimation of the radiation dose to the tumour cells and normal tissues is important. To determine the dose to any tissue from the radionuclide 125I is not simple, since the major emissions are very short-range Auger electrons. The cytotoxicity of 125I is strongly dependent on the position of the decay relative to the DNA, the principal target for cell sterilization. Estimates of the cytotoxicity of 125I based on the traditional MIRD recommended formulation (ICRU Report 32, 1979) may produce gross underestimates if it is incorporated into the DNA via the thymidine precursor 125IUdR. In this work, tissue count and autoradiography (ARG) data from studies by Bagshawe et al were used to estimate tissue doses following the administration of 125IUdR to LS174/T (a colorectal carcinoma) and CC3 (a choriocarcinoma) tumour-bearing animals, after a hydroxyurea block of the normal tissue turnover. The tumour cell toxicity is estimated from ARG data on the degree of 125I incorporation into the cell nucleus. Major drawbacks with 125I for this type of therapy are the long 60-day half-life, leading to radiological and waste disposal problems and the extreme short range of the radiotoxic effects. Possible alternative radiohalogens, 13I, 77Br, 131I and 211At, are suggested in place of 125I in the thymidine analog iododeoxyuridine. Dose calculations are performed and cytotoxicities estimated on the assumption that their biological retention characteristics are the same as for 125IUdR.

Adenocarcinoma↗