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D V Rao

Publications and source records attributed to D V Rao.

At least 73 records · Page 4Linked to original sources
PubMed1992

Absorbed dose calculations for rapidly growing tumors.

One of the most promising areas for cancer therapy with administered radiopharmaceuticals is the treatment of very small tumors and micrometastases. Small tumors and micrometastases, however, may be rapidly growing at the time of treatment, resulting in a substantial change in mass during the period of irradiation. In this work, the formalism required to calculate the average absorbed dose to rapidly growing tumors is developed and applied to an in vitro tumor model. Further application to in vivo human myeloma tumors reveals that tumor growth may have a significant effect on the average dose delivered to the tumor from incorporated radionuclides. These considerations may assist in establishing dose-response relationships necessary for radiopharmaceutical cancer therapy.

Cell Division↗
PubMed1991

Radiotoxicity of 125I-iododeoxyuridine in pre-implantation mouse embryos.

The radiotoxicity of DNA incorporated 125I in cultured pre-implantation two-cell mouse embryos was investigated and compared with external gamma-irradiation. The uptake of 125IdU in the two-cell stage embryos was determined as a function of incubation time and concentration of radioactivity (MBq/ml) in the medium. The absorbed dose to the embryos was calculated using conventional procedures. The embryo survival curves show that the dose at 37% survival is only about 15 cGy for 125IdU, whereas for 137Cs-photons it is 175 cGy. The extreme toxicity observed is thought to be due to the localized energy deposition of the numerous low energy Auger electrons emitted in the decay of 125I. These results are consistent with earlier observations in mouse testis and cultured cells and point to the need for assessing the radiation risk from incorporated Auger electron emitting radionuclides based on their subcellular distribution.

Animals↗
PubMed1991

The question of relative biological effectiveness and quality factor for auger emitters incorporated into proliferating mammalian cells.

The problem of determining RBE values for Auger emitters incorporated into proliferating mammalian cells is examined. In general, the reference radiation plays a key role in obtaining experimental RBE values. Using survival of cultured Chinese hamster V79 cells as the experimental model, new data are provided regarding selection of a reference radiation for internal Auger emitters. These data show that gamma rays delivered acutely (137Cs) are more than twice as lethal as gamma rays delivered chronically with an exponentially decreasing dose rate (99mTc). The results confirm that the reference radiation should be delivered chronically in a manner consistent with the extended exposure received by the cells in the case of incorporated radionuclides. Through a direct comparison of the radiotoxicity of Auger emitters and alpha emitters, the high RBE values reported for DNA-bound Auger emitters are confirmed. These studies reveal that the DNA binding compound [125I]iododeoxyuridine (125IdU) is about 1.6 times more effective in killing V79 cells than 5.3 MeV alpha particles from intracellularly localized 210Po-citrate. In addition, toxicity studies with the radiochemicals 125IdU and [125]-iododeoxycytidine (125IdC) establish the equivalence of the radiosensitivity of thymine and cytosine base sites in the DNA. In view of these results, and information already available, the question of establishing quality factors for Auger emitters is considered. Finally, a method for calculation of the dose equivalent for internal Auger emitters is advanced.

Animals↗
PubMed1991

Induction of sperm head abnormalities by incorporated radionuclides: dependence on subcellular distribution, type of radiation, dose rate, and presence of radioprotectors.

In contrast to the biological effects caused by exposure to external beams of radiation, the effects of tissue-incorporated radionuclides are highly dependent on the type of radiation emitted and on their distribution at the macroscopic, microscopic, and subcellular levels, which are in turn determined by the chemical nature of the radionuclides administered. Induction of abnormalities of sperm heads in mice is investigated in this work after the injection of a variety of radiochemicals including alpha emitters. When the initial slopes of the dose-response curves are used to compare the relative biological effectiveness (RBE) of different radiocompounds, the alpha particles emitted in the decay of 210Po are more effective than Auger electrons emitted by 125I incorporated in the DNA of the spermatogonial cells, and both emissions are more effective than X rays. It is also shown that the Auger emitters (125I, 111In) distributed in the cell nucleus are more efficient in producing abnormalities than the same radionuclides localized in the cytoplasm. These findings are consistent with our earlier observations, where spermatogonial cell survival is assayed as a function of the testicular absorbed dose. Further, chronic irradiation of testis with gamma rays from intratesticularly administered 7Be is about three times more effective in causing abnormalities than a single acute exposure to 120-kVp X rays. The resulting RBE values correlate well with our data on sperm head survival with the same radiocompounds. Finally, the radioprotector cysteamine, when administered in small, nontoxic amounts, significantly reduces the incidence of sperm abnormalities from alpha-particle radiation as well as emissions from 125I incorporated into DNA, the dose reduction factors being 10 and 14, respectively.

Alpha Particles↗
PubMed1990

Biological consequence of nuclear versus cytoplasmic decays of 125I: cysteamine as a radioprotector against Auger cascades in vivo.

When the radionuclide 125I is localized in mouse testis as 125I-iododeoxyuridine (an analogue of thymidine) and incorporated into the DNA of spermatogonial cells, the cytocidal effects are as severe as those due to densely ionizing alpha particles. In contrast, 125I confined to the cytoplasm of these cells is much less radiotoxic, the efficacy being the same as for selective irradiation of the testis with sparsely ionizing external X rays. The biological effects, in both cases, are strongly mitigated upon pretreatment of the testes with very small amounts (0.75 microgram) of cysteamine, a radioprotector. These findings suggest an important role for such chemical agents in radiation protection and in understanding the mechanisms of radiation damage involving radionuclides incorporated in tissue.

Animals↗
PubMed1989

In-vivo radiotoxicity of DNA-incorporated 125I compared with that of densely ionising alpha-particles.

When the atomic nucleus of 125I decays by orbital electron capture followed by internal conversion, numerous very-low-energy electrons (Auger electrons) are emitted, so that the energy density in the immediate vicinity of the decay site is extremely high. 125I incorporated into DNA was as effective as densely ionising 5.3 MeV alpha-particles from 210Po in reducing the sperm-head population in mice. Hence the biological risks of Auger-electron emitting radionuclides widely used in biology and medicine ought to be reassessed.

Animals↗
PubMed1989

Carcinoscorpius rotunda cauda amoebocyte lysate for detection of endotoxins--its preparation, stability, sensitivity and comparison with Limulus amoebocyte lysate.

Carcinoscorpius amoebocyte lysate (CAL) was prepared from C. rotunda cauda by a modification of the method described by Mahalanabis et al. [Indian J Med Res, 70 (1979) 35]. Seasonal variation as well as batch variation was observed in the yield of haemolymph and the total lysate protein. In the presence of E. coli lipopolysaccharide (pure, free endotoxin) and E. coli and Salmonella cell suspensions (bound endotoxin), the CAL formed a gel after incubation at 37 degrees C. The gelling time varied from 10-90 min depending on the concentration of endotoxin used; higher concentrations formed gel more rapidly. The endotoxin detection capacity (sensitivity) of the lysate preparations was influenced by the season in which prepared, but not by the total protein content. Ten fold increase in the sensitivity was achieved by a purification step using chloroform. Although subsequent frozen storage with or without lyophilization did not alter the initial sensitivity, it was either decreased considerably or lost totally when the lysate was stored for 4 months at 4 degrees C or for 2 months at 30 degrees C. Under the same conditions, Limulus lysate was more stable. The lost sensitivity could not be regained by the incorporation of divalent cations (Ca2+ and Mg2+). The CAL preparations in general were able to detect as little as 10-100 pg of endotoxin or as few as 10(3) cells of E. coli or 10(4) cells of Salmonella and were comparable to LAL. CAL could be used successfully in lieu of Limulus amoebocyte lysate in the detection and assay of endotoxins.

Animals↗
PubMed1988

Cytotoxicity of some indium radiopharmaceuticals in mouse testes.

The biological effects of [111In]oxine, [111In]citrate, and [114mIn]citrate localized in mouse testes as well as the effects of external x-rays are investigated. The in vivo radiotoxicity of [111In] oxine is far greater than the chemotoxicity of oxine. Of these radiolabeled compounds, [111In] oxine is the most effective in reducing the sperm-head population, the mean lethal dose (D37) to the organ being about 0.16 Gy at 37% survival of the sperm heads. The corresponding values of D37 for [111In]citrate, [114mIn]citrate and x-rays are approximately 0.34, 0.57, and 0.67 Gy, respectively. The present results affirm our earlier finding of the inadequacy of conventional dosimetry in estimating the biologic consequences of Auger-electron emitters in vivo. The very different radiotoxicities of [111In]oxine and [111In]citrate draw attention to the role of the chemical nature of the radiolabeled compounds in the expression of biologic effects in vivo, an aspect that is not considered explicitly in the formulation of conventional dosimetry.

Animals↗
PubMed1987

Chromium-51 dosimetry of lymphocytes labeled incidentally during nuclear medicine procedures.

Conventional dosimetry based on MIRD procedure fails to consider the localized energy deposition from the radionuclides decaying by the emission of Auger electrons. The cellular dosimetry of human peripheral blood lymphocytes labeled with 51 Cr, an Auger electron emitter, was calculated. Conventional dosimetric calculations reveal a dose of 0.024-0.17 rad/h/tube. In contrast the lymphocyte dose ranged from 0.053-0.339 rad/h with projected cumulative values of 51-324 rad for surviving lymphocytes.

Chromium Radioisotopes↗
PubMed1985

Palliative radiotherapy for inoperable carcinoma of the lung: final report of a RTOG multi-institutional trial.

Between June 1973 and February 1979, 409 patients with inoperable advanced non-oat cell carcinoma of the lung were randomized on RTOG protocol 73-02. Three treatment arms were evaluated: 40 Gy split course, 30 Gy continuous course, and 40 Gy continuous course. Patients were also randomized to receive cytoxan or no further therapy following irradiation. Three hundred sixteen patients were evaluable. Palliation of symptoms was achieved in 60% with 1/4 of the patients becoming symptom-free. Complete regression of local and regional tumor was produced in 15% and partial regression in 26%. There is no significant difference between the treatment arms in these objective response rates. Median survival times were approximately 6 months. No significant benefit was demonstrated by the adjuvant use of Cytoxan. Although the number of complete responses produced was relatively small, patients achieving a complete response had a significantly longer median survival than the remaining patients, i.e., 14.5 months versus 6 months. Significant toxicity occurred in fewer than 6% of patients. Radiation pneumonitis counted for the majority of these adverse reactions. Toxicity occurred somewhat more often in the group treated with 40 Gy split course therapy. Implications for further studies are discussed.

Adenocarcinoma↗
PubMed1985

In vivo effects of iron-55 and iron-59 on mouse testes: biophysical dosimetry of Auger electrons.

When the Auger-electron emitter, 55Fe, and the beta-emitter, 59Fe, are similarly distributed in the testes of mice, the conventionally calculated average radiation dose to the organ from 55Fe is about 2.6 times more effective in reducing the sperm-head count than the dose from 59Fe. This finding emphasizes the ability of low-energy Auger electrons to damage radiosensitive targets of cells through localized irradiation. The observed efficacy is understandable in terms of dosimetric models based on intracellular distribution studies of the radionuclides.

Animals↗
PubMed1983

Comparative cost analysis of hemilaryngectomy and irradiation for early glottic carcinoma.

The cost of hemilaryngectomy (15 patients) was compared to that of radiation treatment (18 patients) in epidermoid carcinoma confined to the true vocal cord with normal mobility (T1N0). An average of $3,495 was saved if radiation therapy was chosen; savings in terms of working hours were also substantial. We maintain that, if different treatment methods yield the same cure rate and quality of life, then cost should be the next strong consideration in choosing a particular treatment method.

Carcinoma, Squamous Cell↗
PubMed1983

Role of radiation in the management of early vocal cord carcinoma.

From 1952-1978, 177 patients with epidermoid carcinoma confined to the true vocal cords with normal mobility (T1NO) were treated with radiation alone. Five- and 10-year adjusted actuarial survival rates for all patients were 97 and 95%, respectively. The tumor recurred in the larynx and/or neck in 16% of patients with T1a (one cord involved) and 23% of the patients with T1b (both vocal cords involved) disease. Radiation failures were surgically salvaged in 89% of patients with T1a disease without anterior commissure involvement, in 60% of those with T1a disease with anterior commissure involvement and in 57% of those with T1b disease. Tumor was ultimately controlled in 97% of the patients with T1a and 90% of the patients with T1b disease. Voice was preserved in 93% of the patients with T1a disease and 77% of patients with T1b disease. Of 121 patients evaluated for voice quality, 77% had good and 22% had fair voice, while only one patient had poor quality of voice. Patients with fair or poor quality voice usually had had salvage hemilaryngectomy. We recommend radiation for all patients with early vocal cord carcinoma.

Adult↗
PubMed1983

Radiotoxicity of thallium-201 in mouse testes: inadequacy of conventional dosimetry.

When TI-201 is concentrated in mouse testes, the low-energy Auger electrons following its electron-capture decay are found to be much more effective in causing loss of testicular weight and reduction of sperm heads than the energetic beta particles from similarly distributed TI-204. These results are contrary to expectations based on conventional dosimetry of tissue-incorporated radionuclides, and point to possible underestimation of risks by the currently adopted dosimetric procedures, especially in the case of radionuclides decaying by electron capture and internal conversion.

Animals↗
PubMed1982

Prognostic indicators in stage III and localized stage IV breast cancer.

One hundred eighty-three patients with Stage III and nonmetastatic Stage IV breast cancer, seen between 1960-1975 at the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, were retrospectively analyzed to determine the prognostic significance of the following clinical features: (1) "grave signs" (skin ulceration, skin fixation, chest wall fixation, and edema); (2) size of primary tumor; (3) nodal stage; and (4) inflammatory changes. Since therapy among 147 patients with noninflammatory cancer comprised of either irradiation alone (54 patients) or surgery plus irradiation (93 patients), all the above factors were analyzed also with respect to the method of treatment. In 147 patients with noninflammatory carcinoma, the local failure rate, regional failure rate, distant failure rate and five-year disease free survival were all unaffected by the presence or absence of "grave signs," whether treated by irradiation alone or surgery plus irradiation. The size of the primary tumor, in patients treated with irradiation alone, influenced the rate of local failure (44% for tumors 0-8 cm and 76% for tumors greater than or equal to 8 cm) and five-year disease-free survival (30 versus 4%, respectively). Such a statistically significant difference in local failure rate or disease-free survival was not noted when treated with combined modality. N stage also influenced the prognosis in patients treated with irradiation alone since the regional failure rate increased from 9% for N0, N1 to 58% for N2, N3 patients. This was reflected in a decreased disease-free survival (4 versus 30%) for patients with advanced nodal disease who were treated with irradiation alone. No such difference was noted when the nodal disease was treated with a combination of surgery and irradiation. The 36 patients with inflammatory carcinoma had essentially the same incidence of local, regional and distant failure as the 147 patients with noninflammatory carcinoma but the appearance of distant metastases occurred significantly earlier in patients with inflammatory carcinoma than in those with noninflammatory carcinoma. This earlier appearance of distant metastases was reflected in the significantly lower disease-free survival for the patients with inflammatory carcinoma (6 versus 28%). The data from this analysis suggests that consideration should be given to removing the presence of grave signs from the current AJC staging system and substituting in its place the size of the primary tumor (less than 8 cm versus greater than or equal to 8 cm). Further analysis on a large number of patients is needed to substantitate this recommendation.

Breast Neoplasms↗