Glenn V. Dalrymple

Single-photon emission computed tomography gallium imaging versus computed tomography: predictive value in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin's lymphoma.

PURPOSE To evaluate the predictive value of computed tomography (CT) scanning and single-photon emission computed tomography (SPECT) gallium (Ga) scanning in the disease-free survival of patients receiving high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS One hundred forty-three patients undergoing transplant for NHL underwent CT scanning of chest, abdomen, and pelvis, and a SPECT Ga scan before transplantation and at day + 100 after transplant. The failure-free survival (FFS) by scan result was analyzed. RESULTS In the diffuse aggressive lymphoma patients, the 1-year FFS for patients having a positive SPECT Ga scan at day + 100 was 15% compared with a 3-year FFS of 47% for those with a negative scan (P < .001). Patients with a positive CT scan at day + 100 had a 36% 3-year FFS, and those with a negative CT scan had a 39% 3-year FFS (P = not significant [NS]). An analysis of the combination of CT scan and SPECT Ga scan results at day + 100 posttransplant demonstrated a 3-year FFS of 14% if they were both abnormal; if the CT was positive and Ga was negative, the 3-year FFS was 68%; positive Ga with a negative CT was 25%; and both negative was 34% (P = .0015). For the patients with follicular NHL, those with a positive SPECT Ga at day + 100 had a 14% 1-year FFS compared with those with a negative scan, who had a 45% 3-year FFS (P < .001). In the follicular NHL patients, the 3-year FFS of those with a positive CT was 17% compared with a 64% 3-year FFS for patients with a negative CT scan (P < .001). CONCLUSION The use of SPECT Ga scan at day + 100 posttransplant for evaluation of disease activity in patients with diffuse aggressive NHL was highly predictive of eventual outcome and was more predictive than the CT scan results. However, for patients with follicular NHL, the addition of SPECT Ga scanning to CT scanning did not add substantially to the evaluation of transplant outcome.

High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a phase I trial.

PURPOSE A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). PATIENTS AND METHODS After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. RESULTS No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. CONCLUSION Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium 90, and on strategies to optimize access of antibody to target antigens.

Biological Effects of Diagnostic Ultrasound: A Review

Biological effects from experimental ultrasound studies, such as chromosome aberrations and retardation of growth, have been recorded but mostly at levels far in excess of diagnostic intensity. The data surveyed in this review suggest that there is apparently little or no danger associated with diagnostic ultrasound exposure at clinical levels.

Proton Depth-Dose Dosimetry'

A most important consideration in the exposure of any large animal to radiation concerns the distribution of the dose throughout the irradiated volume of the body. This becomes particularly so in the case of protons because of their mode of energy deposition in an absorber. Instead of a more or less exponential decrease of the dose with increasing depth, as with the familiar electromagnetic radiations, protons and other charged particles deposit progressively more energy as they approach the end of their path. Also, total-body exposures with protons that have ranges less than the cross-sectional radius of the irradiated subject produce the somewhat unusual situation of irradiating the entire superficial portion of the body while leaving a sizable quantity of the internal volume untouched. Because biological responses are greatly influenced by the depth-dose distribution, rather extensive measurements were made to determine the dose pattern in the primate, Macaca mulatta, when irradiated with 32-Mev, 55-Mev, 138-Mev, 250Mev, and 400-Mev protons. This communication is concerned with the results of measurements made as part of a series of experiments performed to estimate the effects of protons on primates (1-5).

A review of the USAF/NASA proton bioeffects project: rationale and acute effects

Ionizing radiation represented one of the important hazards facing the first manned lunar mission. A combined USAF/NASA project was conducted from 1963 through 1969 to estimate the relative biological effectiveness (RBE) of the radiations of space. Approximately 2000 primates (Macaca mulatta) and 5000 mice were irradiated with protons and electromagnetic radiations. The proton energies studied were selected to be representative of the proton spectrum in space. Much of the project was concerned with the use of cyclotrons for proton irradiations and with dosimetry. Biological measurements included clinical findings, physiological changes, hematological changes, histopathology, and mortality. When allowance was made for variation of response as a consequence of depth-dose distribution, the RBE for protons was approximately 1. This was anticipated from earlier theoretical studies and radiation therapy in humans with high-energy charged-particle beams.

Pain and Aortofemoral Arteriography: The Importance of Chemical Structure and Osmolality of Contrast Agents

A total of 216 aortofemoral angiograms were performed on 72 patients being triple-injected with different contrast media. The characteristics of the contrast media being studied with relation to injection pain included the anionic component, the cationic component, and osmolality. A double-blind study was carried out with neither the examiner nor the patient being aware of the specific contrast medium being injected. The patients were then questioned as to which contrast agent was most painful. There was a significantly lower incidence of severe injection pain with pure meglumines and contrast media with low osmolality. Variation of the anionic component did not improve injection pain.

Radiation produces breaks in L cell and mouse liver DNA characterized by 5′ phosphoryl termini

Abstract Using the polynucleotide kinase method, we were able to demonstrate the repair of radiation induced DNA breaks in mouse liver DNA and in L cells. The specificity of the enzyme indicates the breaks to have 5′ phosphoryl termini.

Protons and space travel--an introduction.

With the launching of the first artificial satellite less than ten years ago, man started toward the penetration of deep space. The balloon and satellite flights which followed this initial venture have yielded valuable information about the nature of the hostile space environment. These deeply penetrating space probes showed conclusively that one of the significant hazards facing the space traveler is ionizing radiation. Fortunately, the early manned flights were not disturbed by high radiation fields because they were made at relatively low altitudes. As progressively longer space flights are made, however, the probability increases that the occupants of the vehicles will receive larger doses of radiation. Because of this situation, the necessity for learning about the biological effects of protons has emerged.

Effects of Radiation on Asynchronous and Synchronized L Cells under Energy Deprivation

The uncoupler of oxidative phosphorylation, 2,4-dinitrophenol (DNP) has been shown to decrease the radiosensitivity of L cells in spite of producing a severe depression of DNA, RNA, protein, and AT...

Radiation induced breaks increase the priming activity of rat sarcoma DNA in the DNA polymerase reaction

Abstract Radiation produces large numbers of DNA breaks which are characterized by 5′ termini. The presence of these breaks is accompanied by an increase in the ability of the DNA to serve as a primer in the DNA polymerase reaction. Since DNA polymerase adds nucleotides from the 3′ end of the molecule, and since a 3′ OH terminus is required, our results provide additional evidence that some radiation induced DNA breaks are characterized by 5′PO43′OH termini. DNA ligase is very likely responsible for rejoining this type of break.