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PubMed1987

Changes of the blood lymphocyte population following 131I treatment for nodular goiter.

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goiter. The patients received one to three doses of 300-550 MBq of 131I administered at 1 week intervals. Lymphocyte counts were significantly reduced both 1 and 6 weeks after treatment. This reduction was accompanied by a changed composition of the lymphocyte population. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming) was significantly reduced 1 and 6 weeks after 131I-administration. At 6 weeks there was a slight but statistically significant increase of the frequency of T-cells as identified by Leu 1 monoclonal antibodies. This was largely caused by an increased proportion of helper/induced T-cells as identified by Leu 3a monoclonals. 131I-treatment also reduced the capacity of lymphocytes to secrete immunoglobulins (Ig) upon PWM-stimulation. The most pronounced effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with PHA and ConA were not significantly changed. We conclude that these changes observed, with the exception of mitogen reactivity, are essentially similar to those occurring after external radiation therapy for cancer. We speculate that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by emitted beta-particles.

Adult↗
PubMed1989

Calculating radiation absorbed dose for pheochromocytoma tumors in 131-I MIBG therapy.

A protocol for calculating radiation absorbed dose to pheochromocytoma tumors during treatment with 131I-labeled metaiodobenzylguanidine (MIBG) is described. The technique calls for (a) obtaining tumor volumes from Computed Tomography and/or Magnetic Resonance Imaging, (b) computing energy absorbed by assuming complete beta-particle absorption and a standard shape for gamma-ray absorption and (c) scaling from tracer to therapy dose rate by the ratio of administered activities. Also a 131I time-activity curve is obtained from planar, Anger-camera, conjugate-view images of the tumor and a known-strength source, both over a series of days. In addition, to correct for any systematic errors in the calculated uptakes, a larger activity of 123I MIBG is administered separately and quantitative Single Photon Emission Computed Tomography (SPECT) is undertaken. A known-strength source also undergoes SPECT to calibrate the tomograms. Correction for Compton scattering is accomplished by the dual-energy-window technique. The subtraction fraction was found to be 0.7 for the 1/2" crystal camera and the mean reduction in tumor counts for seven tumors from Compton correction was 0.76. The normalization factor needed to bring the conjugate-view activities into agreement with the SPECT values ranged from 0.74 to 1.06. A test study on an anthropomorphic phantom indicated that the error in resultant activities might be estimated as +/- 13%. Application of the protocol led to the calculation of real, or potential (when decision was finally made to not administer therapy) radiation absorbed dose to seven tumors in three patients from an administration of about 8 GBq of MIBG. For two metastatic tumors in a 19-year old patient who did not have her primary cancer resected, the calculated radiation absorbed dose was 170 and 180 Gy. For the four metastatic deposits evaluated in two older patients, both of whom had their primary tumor surgically removed, the values ranged from 18 to 31 Gy.

3-Iodobenzylguanidine↗
PubMed1994

A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media.

PURPOSE: To describe and evaluate a new, simple, inexpensive method for directly measuring the radiation dose and its spatial distribution generated from explanted tissues of animals previously injected with radiolabeled immunoconjugates or other agents. METHODS AND MATERIALS: This technique uses the newly developed radiochromic dye medium (Gafchromic) which responds reproducibly for therapeutic dose exposures, has high spatial resolution, does not require film processing, and is relatively insensitive to ambient light. We have evaluated the dose distribution from LS174T tumors and selected normal tissues in nude mice previously injected with 90Y labeled anti-carcinoembrionic antigen antibodies. Individual tissues from sacrificed animals are halved and the flat section of the tissue is placed onto the dosimetry media and then frozen. The dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from the frozen tissues. The relative darkening of the dosimetry medium depends on the dose deposited in the film. The dosimetry medium is scanned with a commercial flatbed scanner and the image intensity is digitally stored and quantitatively analyzed. Isodose curves are generated and compared to the actual tissue outline. RESULTS: The absorbed dose distribution due to 90Y exposure show only slight gradients in the interior of the tissue, with a markedly decreasing dose near the edges of the tissue. In addition, the isodose curves follow the tissue outline except in regions having radii of curvature smaller than the range of the beta-particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its curvature, are important in determining the minimum dose delivered to the tumor by radiation from 90Y monoclonal antibodies, and hence in evaluating the tumor response to the radiation. The dose and spatial dose distribution were calculated assuming that the total 90Y activity is distributed uniformly throughout a half ellipsoid. The calculated spatial dose distributions for the half ellipsoids were similar to those observed from the dosimetry media that had been exposed to radioactivity contained in the tumors. CONCLUSION: This method provides direct dose evaluation without elaborate summary calculations based on activity measurements from serial slices. The measured radiation dose actually indicates the dose rate at the time of animal sacrifice. Quantitative analysis of radiation emitted from the tissues is relatively fast, making it feasible to examine a number of tissues under a variety of conditions.

Animals↗
PubMed1990

In vivo stability of ferric hydroxide macroaggregates (FHMA). Is it a suitable carrier for radionuclides used in synovectomy?

Ferric hydroxide macroaggregates (FHMA) have been widely used as a carrier for several radionuclides used in radiation synovectomy. Different rates of extra-articular leakage of radioactivity have been observed with 90Y and 165Dy. In order to understand the mechanism(s) involved in the extra-articular leakage of radioactivity, the in vivo stability of FHMA carrier was studied. Following an injection of [59Fe]Fe-FHMA into the knees of normal rabbits, the cumulative leakage of [59Fe]Fe-FHMA was 2.9% at 5 days and 12.3% at 14 days. More than 60% of this activity was in the blood. But when FHMA was double labeled with 59Fe and 166Ho, the 59Fe leakage significantly increased to 18.5% at 5 days and 27% by 14 days. The instability of FHMA is accelerated when it is complexed with 166Ho and may be due to the "mass effect" of 166Ho or due to radiolysis induced by high energy beta particles from 166Ho. These results suggest that FHMA is a suitable carrier only for the short lived radionuclides used in synovectomy.

Animals↗
PubMed2005

Absorbed dose estimates at the cellular level for 131I.

Microdosimetric calculations of 131I have been evaluated for a single cell and for cell clusters. A VsBasic program has been used to calculate stopping power, linear energy transfer, range values and deposited energies per decay for beta particles, Auger and conversion electrons of 131I. The chemical composition of the cell has been taken into account in this model; results were compared with water medium. Besides, total absorbed doses have been calculated for the radionuclides distributed randomly within the cell and clusters. Cross-fire irradiation has been considered for clusters of cells. In this case, absorbed doses per cell within a cluster were found to be significantly higher than absorbed doses per single cell, depending on the cluster size. Results showed that 131I is a promising radionuclide for therapy of tumors from millimeter to centimeter dimensions.

Iodine Radioisotopes↗
PubMed2005

A statistical analysis of the initial biodistribution of 153Sm-EDTMP in a canine.

(153)Sm (t(1/2)=46 h) emits a 103 keV gamma photon and two medium-energy beta particles. Five mCi of Samarium-153 ethylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP) were administered to a clinically normal dog and whole body scans were obtained at 15min, 2h, and 24h post-injection (PI). Regions of interest (ROIs) were drawn representing abdomen, knee, rib, vertebral bodies, bladder, kidney, and liver, in each image. For each ROI, the mean intensity and standard deviation were computed, and a histogram was created. Clinically significant increased uptakes were found in liver and kidney.

Animals↗
PubMed2006

Determination of 222Rn in fresh water: development of a robust method of analysis by alpha/beta separation liquid scintillation spectrometry.

Liquid scintillation spectrometry is used widely for determining (222)Rn in natural waters; however, the benefits of alpha/beta separation have not been fully explored. The extractants toluene and Ultima Gold F were compared, and both performed well for a range of extreme waters. A robust method for calibrating extraction and counting efficiencies has been developed. Detection limits are 20 mBql(-1) (toluene) and 16 mBql(-1) (UGF) for a 60 min count and 600-ml sample, halving the required sample volume.

Alpha Particles↗
PubMed2006

Monoclonal antibodies and immunoconjugates in acute myeloid leukemia.

The use of monoclonal antibodies for patients with acute myeloid leukemia is based on targeting cell-surface antigens preferentially expressed on leukemic blasts while sparing normal cells and tissues. The majority of studies performed to date have used antibodies reactive with the CD33 antigen. Phase II studies have demonstrated antileukemic responses with all agents, although less so with unlabeled antibodies. The most promising results have been obtained in the treatment of minimal residual disease in patients with acute promyelocytc leukemia. Antibody-targeted chemotherapy with gemtuzumab ozogamicin has also shown significant activity in patients with relapsed acute myeloid leukemia. Radioimmunotherapy with beta-particle emitters may be most effective for the treatment of bulky disease or as part of a conditioning regimen for hematopoietic stem-cell transplantation, whereas radioimmunotherapy with alpha-particle emitters may be better suited to the treatment of small-volume or minimal residual leukemia. Whether or not monoclonal antibody therapy will improve disease outcome compared with conventional treatment regimens remains to be demonstrated by well-designed clinical trials.

Acute Disease↗
PubMed2005

Calibration of the photon component of 198Au stents.

PURPOSE: 198Au has promising characteristics for radioactive stent material, having properties as a mixed beta-particle and gamma emitter. Calibration of these radioactive stents is required to provide accurate clinical dosimetry. METHODS AND MATERIALS: We have developed an electroplating technique to incorporate stable gold onto stents followed by activation to 198Au in the University of Wisconsin nuclear reactor. The calibration method is a modification of the NIST traceable, in-air calibration technique for high-dose-rate (HDR) 192Ir sources. RESULTS: The air-kerma strength of HDR and low-dose-rate (LDR) sources was measured for proof of principle and found to agree to within 3% of values obtained with other NIST traceable calibration techniques. The photon component of two 198Au radioactive stents was measured over a period of 3 days. CONCLUSION: The air-kerma strength of HDR and LDR sources was measured for proof of principle and found to agree to within 3% of values obtained with other NIST traceable calibration techniques.

Calibration↗
PubMed2005

Radiation: basic principles.

This communication describes some basic principles of radiation that are relevant for understanding its use in vascular brachytherapy. It describes various characteristics of gamma-rays and beta-particles, including their interaction with matter such as tissues. It also explains different terms and concepts such as radioactivity, half-life, absorbed dose, range which would help the brachytherapy practitioners appreciate the physics aspects of the therapy.

Brachytherapy↗
PubMed2004

A simple calibration method for 106Ru-106Rh eye applicators.

Ru-Rh eye applicators are used for the radiotherapy of eye malignancies such as melanomas. We present a method of dosimetry of these beta particle emitting applicators. Method is based on a Plexiglas phantom (constructed for this purpose) containing spherical shells and very small, 1x1x1mm3 thermoluminescent dosimeters (TLD) as dosimeters. We determined 3-D depth doses and interpolated depth dose functions. Surface dose rate inhomogeneities and the consequences were considered and discussed. A possible influence of photon component of the emission on the results was analysed. The method has overall combined uncertainty + or -6% which is comparable, and slightly better, than other recent dosimetric methods.

Calibration↗
PubMed2005

Staging and treatment of differentiated thyroid carcinoma with radiolabeled somatostatin analogs.

In patients with progressive metastatic (or recurrent) differentiated thyroid carcinoma that either do not take up radioiodine or are unresponsive to continued radioiodine therapy, staging is difficult and treatment options are few. However, in most of these patients uptake of radiolabeled somatostatin analogs is evident on somatostatin-receptor scintigraphy (SRS). Using SRS, patients with sufficient uptake of radiolabeled somatostatin analogs can be selected for high-dose peptide receptor radionuclide therapy (PRRT) as an alternative targeted-treatment option. PRRT with the beta-particle-emitting radionuclides (90)yttrium ((90)Y) and (177)lutetium ((177)Lu) gives the best results in terms of objective tumor response. Promising, novel, radiolabeled somatostatin analogs that have a broader receptor affinity profile and, thus, a potentially wider therapeutic range are being tested clinically.

Adenocarcinoma, Follicular↗
PubMed1990

Radioiodinated tracers for myocardial imaging.

Recent advances in the efficient production of high purity radioiodine (123I) and new efficient radiolabeling techniques have allowed the development of new classes of cardiovascular radiopharmaceuticals. These include 123I-labeled fatty acids to assess myocardial metabolism, 123I-metaiodobenzylguanidine (MIBG) for myocardial neuronal activity, labeled monoclonal antibodies for myocardial necrosis, and labeled lipoproteins for receptor concentration. 123I-labeled fatty acids and MIBG are under clinical investigation with encouraging results. 123I- and 111In-labeled fragments of monoclonal antibodies to myosin have been used for imaging myocardial necrosis in humans. The development of radiotracers for imaging of cholinergic and adrenergic receptors is still in the experimental stage. Recent advances in imaging instrumentation and radiopharmaceuticals have resulted in cardiac imaging applications beyond blood pool ventriculography, perfusion, and infarct-avid imaging. Developments of radioiodine (123I)-labeled agents promise to play an important role in the assessment of myocardial metabolism, neuronal activity, and receptor concentration. The chemistry of iodine is well defined compared with that of 99mTc; therefore, iodine isotopes are well suited for labeling biologically important molecules. Among the iodine isotopes, 123I has nearly ideal nuclear properties for nuclear medical applications with a 13.3-hour half-life (T1/2) and 159 keV gamma emission (83%). Despite the nearly ideal chemical and nuclear properties of 123I, the widespread application of 123I-based radiopharmaceuticals in clinical practice has been limited by high production costs (123I is produced in a cyclotron), relatively limited availability, and the presence of undesirable radionuclidic impurities (124I, T1/2 = 4.2 days; 125I, T1/2 = 60 days; 126I, T1/2 = 13.1 days). The relatively long T1/2 and beta particle emission can substantially increase the higher radiation burden to the patient. High energy gamma rays (greater than 600 KeV) from these impurities can degrade images obtained using low energy collimators. Recent developments in production techniques have greatly reduced the levels of the undesirable radionuclides in 123I. Ready availability of pure 123I at modest cost, in concentrations suitable for the radio-labeling of a variety of useful biomolecules, should enhance the clinical applications of 123I-labeled compounds. Molecules labeled with 123I that are useful in cardiac imaging studies are fatty acid analogs, monoclonal antibodies, receptor binding agents, and norepinephrine analogs. This article will discuss developments in radioiodine (123I)-labeled radiotracers for myocardial imaging.

Heart↗
PubMed1979

Radiotherapeutic agents: properties, dosimetry, and radiobiologic considerations.

Radioactive nuclides for treatment have occupied an important but somewhat diminishing role in the total practice of nuclear medicine. Although theoretically they should have important potentialities, particularly in the treatment of various forms of cancer, their development in this field has not kept pace with the progress in other treatment modalities in radiation oncology. Indications for the selection of appropriate isotopes for therapy revolve about the emission of beta particles of sufficient energy, which are administered in a chemical form that reaches the tumor. Methods of calculation of doses delivered to sites of deposition are discussed in the text. Radiobiologic considerations include the possibility of early deleterious effects from overdosage, and consideration of chromosomal changes of circulating lymphocytes and their implications. Late effects that have been of great public concern are confined almost solely to possible carcinogenesis, and this effect has been minimal in patients receiving therapeutic levels of radioactive drugs. Genetic and developmental effects, also, have been negligible. Complications encountered more frequently have been leukemia after extensive therapy of thyroid carcinoma, and local fibrosis after direct injection of radioactive colloids into tumor tissue.

Adolescent↗
PubMed1968

The mechanism of inactivation of T4 bacteriophage by tritium decay.

Coliphage T4 was used as a model system to study the mechanism of biological inactivation produced by tritium decay. Experimentally, tritiated precursors were incorporated into phage DNA (thymidine-(3)H) or into phage protein ((3)H-amino acids). The ratio of killing efficiencies for decays originating in phage DNA to those originating in phage protein was 2.6. Inactivation by decays from labeled amino acids was assumed to occur exclusively from beta-particle irradiation of phage DNA. If decays originating in DNA are due solely to irradiation of DNA, then the killing efficiencies reflect the energy transfer paths in phage DNA for decays originating in phage DNA and in the protein coat. The energy transfer paths were determined for the two cases with the help of a computer and found to be very nearly equal to the experimentally determined ratio (2.6). The killing efficiencies for decays originating in phage DNA were 0.12 and for decays originating in protein 0.046.

Amino Acids↗
PubMed1985

Glycogen of high molecular weight from mammalian muscle.

Glycogen of high molecular weight has been isolated from mammalian muscle, in contrast to the material of low molecular weight commonly described. The large polysaccharide is similar to liver glycogen in the structure of its individual beta-particles and also, partially, in the mode of assembly into the gross alpha-particles. The large particles may be disrupted by 2-mercaptoethanol, but not to the same extent as their liver counterparts.

Animals↗
PubMed2001

Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling.

Analgesics, Non-Narcotic↗
PubMed1999

Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals.

In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropililydenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic beta-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37 degrees C and I = 150 mmol dm-3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho-APD complex was taken up primarily by the liver due to precipitation or colloid formation.

Animals↗