Biomedical subjects

J L Humm

Publications and source records attributed to J L Humm.

At least 19 recordsLinked to original sources

PubMed2002

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer.

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Algorithms↗

PubMed2001

Estimate of absorbed dose based on two-dimensional autoradiographic information in internal radionuclide therapy.

In radiation therapies using radionuclides emitting short-range particles, such as radioimmunotherapy or boron neutron capture therapy, the biological effects are strongly affected by the heterogeneity of the absorbed dose distribution delivered to tumor cells. The three-dimensional (3D) information of the source distribution at the cellular level is required to accurately determine the absorbed dose distribution to the individual tumor cells. Two-dimensional distribution of cell and nuclide with a resolution of 1 microm can be obtained from individual tissue sections by microautoradiography. To obtain such information in 3D, an ideal approach would be to align the serial tissue sections from a block and analyze all of them. This is straightforward in theory, but extremely difficult in practice. Furthermore, every section in the block has to be processed and analyzed, and the usage of the data from this laborious work is very inefficient. An approach presented here is to estimate the absorbed dose based on individual sections without 3D reconstruction. It is realistically workable since it avoids the most difficult task of alignment for the serial tissue sections. In addition, the absorbed dose can be estimated based on a limited number of noncontiguous sections. The validity of this approach has been tested by a Monte Carlo simulation for two representative radionuclide configurations: (a) a uniform distribution of sources and (b) a cell membrane bound source distribution. With only a limited number of sampling sections, the uncertainties in the dose estimation were estimated to approximately 15% for short-range particles.

Autoradiography↗

PubMed2001

Hypoxia-Induced increase in FDG uptake in MCF7 cells.

UNLABELLED: Recent clinical data indicate that tumor hypoxia negatively affects the treatment outcome of both radiotherapy and surgery in various cancers, emphasizing the need for noninvasive detection of tumor hypoxia. Several studies have shown an increased uptake of FDG in hypoxic regions of xenografts, suggesting the use of PET with FDG as a potential technique. In this study, we examine the mechanism underlying the hypoxia-induced increase of FDG uptake in the human breast carcinoma cell line MCF7. METHODS: The uptake of 3H-FDG into MCF7 cells was determined after incubation under hypoxic (0% oxygen) or normoxic conditions, with or without redox agents, for varying time periods. In addition, the effects of the redox agents on the glucose transporter activity and the hexokinase activity were determined independently, and the effects of hypoxia on glucose transporter protein and hexokinase levels were assessed. RESULTS: A more than twofold increase (2.53 +/- 0.79; P < 0.005) in 3H-FDG uptake was observed under hypoxic conditions, but no changes in the cellular levels of glucose transporter proteins or hexokinase were observed. A reducing agent, dithiothreitol (DTT), also caused an increase in 3H-FDG uptake but failed to affect uptake under hypoxic conditions. This indicates that the mechanisms by which hypoxia and DTT affect 3H-FDG uptake might be the same. The oxidizing agent p-chloromercuribenzenesulfonic acid (pCMBS) had no effect on 3H-FDG uptake under normoxic conditions but counteracted the effect of hypoxia. DTT caused an increase in glucose transporter activity, whereas it had no effect on hexokinase activity. pCMBS had no effect on either glucose transporter activity or hexokinase activity. CONCLUSION: The hypoxia-induced increase in 3H-FDG uptake in MCF7 cells is the result, in part, of an increase in glucose transporter activity resulting from the modification (reduction) of thiol group(s) in the glucose transport protein(s). Modulation of hexokinase activity is probably not involved in the hypoxia-induced increase in 3H-FDG uptake in these cells.

4-Chloromercuribenzenesulfonate↗

PubMed2001

Relative therapeutic efficacy of (125)I- and (131)I-labeled monoclonal antibody A33 in a human colon cancer xenograft.

UNLABELLED: A33, a monoclonal antibody that targets colon carcinomas, was labeled with (125)I or (131)I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. METHODS: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of (125)I-A33 (9.25-148 MBq) or (131)I-A33 (0.925-18.5 MBq), (125)I- and (131)I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were assessed using the endpoints of tumor growth delay and cure. RESULTS: Tumor growth delay increased with administered activity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for (125)I-A33 to produce therapeutic effects that were equivalent to those of (131)I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 antibody had no effect on tumor growth. Approximately 10 times more activity of (125)I-A33 produced toxicity similar to that of (131)I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. CONCLUSION: Treatment with (125)I-A33 resulted in a relative therapeutic gain of approximately 2 compared with (131)I-A33 in this experimental system.

Animals↗

PubMed2001

PET imaging of (86)Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: comparison between (86)Y and (111)In radiolabels.

UNLABELLED: Absorbed doses in (90)Y radioimmunotherapy are usually estimated by extrapolating from (111)In imaging data. PET using (86)Y (beta(+) 33%; half-life, 14.7 h) as a surrogate radiolabel could be a more accurate alternative. The aim of this study was to evaluate an (86)Y-labeled monoclonal antibody (mAb) as a PET imaging agent and to compare the biodistribution of (86)Y- and (111)In-labeled mAb. METHODS: The humanized anti-Lewis Y mAb hu3S193 was labeled with (111)In or (86)Y through CHX-A"-diethylenetriaminepentaacetic acid chelation. In vitro cell binding and cellular retention of radiolabeled hu3S193 were evaluated using HCT-15 colon carcinoma cells, a cell line expressing Lewis Y. Nude mice bearing HCT-15 xenografts were injected with (86)Y-hu3S193 or (111)In-hu3S193. The biodistribution was studied by measurements of dissected tissues as well as by PET and planar imaging. RESULTS: The overall radiochemical yield in hu3S193 labeling and purification was 42% +/- 2% (n = 2) and 76% +/- 3% (n = 6) for (86)Y and (111)In, respectively. Both radioimmunoconjugates specifically bound to HCT-15 cells. When cellular retention of hu3S193 was studied using (111)In-hu3S193, 80% of initially cell-bound (111)In activity was released into the medium as high-molecular-weight compounds within 8 h. When coadministered, in vivo tumor uptake of (86)Y-hu3S193 and (111)In-hu3S193 reached maximum values of 30 +/- 6 and 29 +/- 6 percentage injected dose per gram and tumor sites were easily identifiable by PET and planar imaging, respectively. CONCLUSION: At 2 d after injection of (111)In-hu3S193 and (86)Y-hu3S193 radioimmunoconjugates, the uptake of (111)In and (86)Y activity was generally similar in most tissues. After 4 d, however, the concentration of (86)Y activity was significantly higher in several tissues, including tumor and bone tissue. Accordingly, the quantitative information offered by PET, combined with the presumably identical biodistribution of (86)Y and (90)Y radiolabels, should enable more accurate absorbed dose estimates in (90)Y radioimmunotherapy.

Animals↗

PubMed2000

Targeted radioimmunotherapy for leptomeningeal cancer using (131)I-3F8.

BACKGROUND: Intrathecal antibody-based targeted therapies may have clinical potential for patients with leptomeningeal (LM) cancer. PROCEDURE: Five patients with GD2-positive LM tumors were injected with 1-2 mCi intra-Ommaya (131)I-3F8, a murine IgG3 antibody specific for GD2. Serial cerebrospinal fluid (CSF) and serum samples and SPECT imagings (4, 24, and 48 hr) were performed to predict radiation doses to the tumor and normal brain and blood prior to the administration of larger therapeutic doses. RESULTS: Side effects included self-limited fever, headache, and vomiting. Focal (131)I-3F8 uptake consistent with tumors was seen along the craniospinal axis in four patients. Calculated radiation dose to the CSF was 14.9-56 cGy/mCi and to blood and other organs outside the CNS less than 2 cGy/mCi. CONCLUSIONS: Intraventricular (131)I-3F8 successfully detected LM disease and resulted in a large favorable CSF/blood ratio. Intraventricular (131)I-3F8 may have clinical utility in the diagnosis and radioimmunotherapy of GD2-positive LM cancers. Med. Pediatr. Oncol. 35:716-718. 2000.

Antibodies↗

PubMed2000

Use of PET to monitor the response of lung cancer to radiation treatment.

Approximately 170,000 people are diagnosed with lung cancer in the United States each year. Many of these patients receive external beam radiation for treatment. Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is increasingly being used in evaluating non-small cell lung cancer and may be of clinical utility in assessing response to treatment. In this report, we present FDG PET images and data from two patients who were followed with a total of eight and seven serial FDG PET scans, respectively, through the entire course of their radiation therapy. Changes in several potential response parameters are shown versus time, including lesion volume (V(FDG)) by PET, SUVav, SUVmax, and total lesion glycolysis (TLG) during the course of radiotherapy. The response parameters for patient 1 demonstrated a progressive decrease; however, the response parameters for patient 2 showed an initial decrease followed by an increase. The data presented here may suggest that the outcome of radiation therapy can be predicted by PET imaging, but this observation requires a study of additional patients.

Aged↗

PubMed2000

Evaluation of 11C-colchicine for PET imaging of multiple drug resistance.

UNLABELLED: Overexpression of P-glycoprotein (P-gp) can confer multiple drug resistance (MDR) phenotype on cancer cells and tumors by reducing intracellular accumulation of various cytotoxic agents. Early diagnosis of MDR in the clinic will serve to improve the efficacy of chemotherapeutic intervention and the quality of life of patients. In this article we describe use of a positron-emitting MDR tracer, 11C-colchicine (CHC), to evaluate MDR by PET imaging. Unlike existing MDR tracers such as 99mTc-sestamibi, this compound is electroneutral, with biodistribution not affected by perturbations of membrane potential. METHODS: In vitro studies showed that resistance to CHC is correlated to resistance to Taxol (paclitaxel). The results of biodistribution experiments were found to be consistent with previously reported experiments with CHC labeled with other isotopes. On the basis of in vitro experiments with a series of drug-resistant variants of the human neuroblastoma BE (2)-C cell line, a mathematic model of 11C-CHC distribution in tumors was formulated. Dynamic PET 11C-CHC imaging experiments were performed with nude rats xenografted with the BE (2)-C-sensitive and -resistant strains. Each scan was accompanied by a transmissions scan and a static FDG scan. These scans allowed improved image localization. RESULTS: We observed an approximately 2-fold difference between 11C-CHC accumulation in sensitive and resistant tumors. Imaging data were analyzed using the mathematic model, and various parameters characterizing resistance could be identified and estimated. In particular, the parameter r, proportional to the level of resistance of the tumors, was obtained. We showed that the ratio of these r parameters determined from the sensitive and resistant tumors was identical to the ratio of CHC accumulation in the corresponding sensitive and resistant cell lines used for xenografting. CONCLUSION: These in vivo experiments provided additional evidence for the indirect effect of P-gp action on CHC-to-tubulin binding, which in turn determines CHC uptake in tumors. The significance of these findings and future plans is discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Single-dose versus fractionated radioimmunotherapy: model comparisons for uniform tumor dosimetry.

UNLABELLED: Targeting molecules with reduced immunogenicity will enable repetitive administrations of radioimmunotherapy. In this work a mathematical model was used to compare 2 different treatment strategies: large single administrations (LSAs) and rapid fractionation (RF) of small individual administrations separated by short time intervals. METHODS: An integrated compartmental model of treatment pharmacokinetics and tumor response was used to compare alternative treatments that delivered identical absorbed doses to red marrow. RESULTS: Based on the key assumption of uniform dose distributions, the LSA approach consistently produced smaller nadir values of tumor cell survival and tumor size. The predicted duration of remission was similar for both treatment structures. These findings held for both macroscopic and microscopic tumors and were independent of tumor cell radiosensitivity, proliferation rate, rate of tumor shrinkage, and uptake characteristics of radiolabeled material in tumor. CONCLUSION: Clinical situations for which each treatment is most appropriate may be tentatively identified. An LSA using a short-range-emitting radionuclide would be most appropriate for therapy of microscopic disease, if uptake is relatively homogeneous. RF using a longer range emitter would be most appropriate for macroscopic disease, if uptake is heterogeneous and varies from one administration to another. There is a rationale for combining LSA and RF treatments in clinical situations in which slowly growing macroscopic disease and rapidly growing microscopic disease exist simultaneously.

Dose-Response Relationship, Radiation↗

PubMed2000

Radioiodine uptake in thyroid remnants during therapy after tracer dosimetry.

UNLABELLED: Our objective was to evaluate the effect of a diagnostic tracer dose of 131I on the uptake of the therapeutic dose of 1311 in the ablation of a thyroid remnant or residual tumor in patients with differentiated thyroid cancer. METHODS: Twelve consecutive patients referred for a dosimetric study and subsequent radioiodine treatment of focal neck uptake of 131I were studied. The 24-h (in 1 case, 48-h) neck activity was calculated by the region-of-interest method, after both dosimetric and therapeutic administrations. The focal activity in the neck was corrected for decay and compared with the total activity administered to obtain the percentage uptake at 24 h. This procedure was performed for both the scanning dose (range, 19.8-196.1 MBq; mean, 85.1 MBq; median, 40 MBq) and the therapeutic dose (range, 1.073-5.713 GBq; mean, 2.991 GBq). The uptake of the therapeutic dose was then expressed as a percentage of the uptake of the diagnostic dose (%T/D). Counting rate linearity was established up to 350 MBq in the field of view of the gamma camera used in the study. RESULTS: Thirteen of a total of 16 lesions exhibited reduced uptake from the therapeutic dose, 2 remained the same, and in 1 the uptake actually increased from 0.26% to 1.01%. The %T/D ranged from 7.0% to 388.5%, with a mean of 71%. If the lesion with increased uptake is excluded, the range becomes 7.0%-102.1%, with a mean of 50%. Linear regression between the percentage uptake of the diagnostic dose to that of the therapeutic dose results in a slope of 0.42, with a correlation coefficient of only 0.75. We were unable to accurately calculate the radiation dose to the lesion from the diagnostic activity of 131I, because of uncertainty about the tumor mass. CONCLUSION: The percentage uptake of the therapeutic dose is on average only one half of that predicted from the dosimetric uptake in thyroid remnants after surgery, even though the median dosimetric dose was only 40 MBq. This reduced uptake should be accounted for in the therapeutic prescription for thyroid ablation or treatment of residual thyroid cancer. We postulate that this effect is caused by radiation damage from the tracer dose during dosimetry.

Humans↗

PubMed2000

Optimizing the sequence of combination therapy with radiolabeled antibodies and fractionated external beam.

UNLABELLED: The purpose of this study was to determine the optimum sequence for combined modality therapy with radiolabeled antibodies and fractionated external beam radiation. METHODS: The uptake and distribution of a nontherapeutic activity of 125I-labeled tumor-associated A33 monoclonal antibody was determined in SW1222 human colon carcinoma xenografts in nude mice for 4 study groups: group 1, radiolabeled antibody alone; group 2, radiolabeled antibody administered (day 0) immediately before the first of 5 daily fractions of 2-Gy, 320-kilovolt peak x-rays; group 3, radiolabeled antibody administered after the fifth radiation fraction (day 5); and group 4, radiolabeled antibody administered 5 d after irradiation (day 10). Tumors were excised 5 d after antibody administration. Tumors were frozen and sectioned for histology and phosphor plate autoradiography. The percentage of A33 antigen-expressing cells was estimated by immunohistochemical staining. RESULTS: The average tumor uptake values relative to control group 1 were 1.47 (group 2), 0.78 (group 3), and 0.21 (group 4), which illustrates that tumor uptake is increased by almost 50% when the antibody is present in the blood at the start of irradiation. Five days into a fractionated irradiation protocol, antibody uptake was reduced, falling more significantly on day 10. Phosphor plate autoradiographs showed decreased uptake uniformity for groups 3 and 4. Immunohistochemical data showed a reduction in A33 antigen-positive cells from 85%, 64%, 50%, to 41% for groups 1-4, respectively. CONCLUSION: Maximum radiolabeled antibody tumor uptake was achieved when the antibody was administered just before radiation therapy. This might be explained by a transient increase in capillary leakage to macromolecules, followed by a reduction at later times, possibly the result of capillary damage and occlusion.

Animals↗

PubMed1999

Metabolic activation of the subependymal zone after cortical injury.

The subependymal zone (SEZ) of the adult mammalian forebrain contains a population of progenitor cells that proliferate in response to brain injury. This study examined the effect of cortical injury on metabolic activity in the SEZ using quantitative histochemistry of cytochrome oxidase. The SEZ showed significantly enhanced cytochrome oxidase activity in rats with electrolytic cortical injuries relative to sham-operated controls, while other brain regions showed no such changes. The results indicate that the SEZ had increased oxidative energy demands, and thus provide metabolic evidence that SEZ cells are activated in response to brain injury.

Animals↗

PubMed1999

Use-dependent exaggeration of brain injury: is glutamate involved?

Extreme overreliance on the impaired forelimb following unilateral lesions of the forelimb representation area of the rat sensorimotor cortex (FL-SMC) leads to exaggeration of the initial cortical injury. Glutamate has repeatedly been implicated in the secondary processes leading to neuronal death following traumatic insult, chiefly because of the neuroprotective properties of excitatory amino acid antagonists in a variety of animal models of brain injury. The present study investigated the possibility that NMDA receptor-mediated processes are involved in use-dependent exaggeration of neuronal injury. Rats were fitted with one-sleeved casts that immobilized the intact forelimb for the first 7 days following FL-SMC lesion, a procedure previously shown to result in use-dependent exaggeration of injury and more severe and persistent limb-use deficits. In the present investigation, administration of MK-801 (1 mg/kg ip once daily on alternate days) during the casting period spared neural tissue surrounding the lesion and enhanced functional recovery of the impaired forelimb. These results suggest a role for NMDA receptor-mediated processes in use-dependent exaggeration of injury.

Analysis of Variance↗

PubMed1999

Cortical injury impairs contralateral forelimb immobility during swimming: a simple test for loss of inhibitory motor control.

Most animal models of focal injury to the sensorimotor cortex have been aimed at detecting non-use or impairment of the limbs in specific tasks or during spontaneous exploratory behaviors. However, the inability to hold a limb still can be an equally disabling movement disorder. The present study investigated the loss of control of limb immobility that occurs following damage to the forelimb region of the rat sensorimotor cortex (FL-SMC). When swimming forward in a tank of water, adult rats typically hold both forepaws mostly motionless underneath the chin, using primarily the hindlimbs for stroking movements. Following a unilateral FL-SMC lesion, rats hold only the non-impaired forelimb immobile under the chin, and make 'immature' stroking movements with the impaired forelimb. We have devised a simple means of assessing and quantifying this deficit. While the criterion for most tests of motor recovery involves appropriate movement of an impaired limb, this test depends on adequate inhibition of movement as the norm, and may be a useful way to assess the loss of inhibitory motor control and the efficacy of potential restorative interventions.

Animals↗

PubMed1999

131I radioimmunotherapy and fractionated external beam radiotherapy: comparative effectiveness in a human tumor xenograft.

UNLABELLED: This article compares the effectiveness of radiation delivered by a radiolabeled monoclonal antibody, 131I-labeled A33, that targets colorectal carcinoma, with that of 10 fractions of conventional 320 kVp x-rays. METHODS: Human colorectal cancer xenografts (SW1222) ranging between 0.14 and 0.84 g were grown in nude mice. These were treated either with escalating activities (3.7-18.5 MBq) of 131I-labeled A33 or 10 fractions of 320 kVp x-rays (fraction sizes from 1.5 to 5 Gy). Tumor dosimetry was determined from a similar group of tumor-bearing animals by serial kill, tumor resection and counting of radioactivity in a gamma counter. The relative effectiveness of the two radiation therapy treatment approaches was compared in terms of tumor regrowth delay and probability of tumor cure. RESULTS: The absorbed dose to tumor per MBq administered was estimated as 3.7 Gy (+/-1 Gy; 95% confidence interval). We observed a close to linear increase in tumor regrowth delay with escalating administered activity. Equitumor response of 1311 monoclonal antibody A33 was observed at average radiation doses to the tumor three times greater than when delivered by fractionated external beam radiotherapy. The relationship between the likelihood of tumor cure and administered activity was less predictable than that for regrowth delay. CONCLUSION: The relative effectiveness per unit dose of radiation therapy delivered by 131I-labeled A33 monoclonal antibodies was approximately one third of that produced by fractionated external beam radiotherapy, when measured by tumor regrowth delay.

Animals↗

PubMed1999

Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: 213Bi-HuM195 (anti-CD33) in patients with leukemia.

UNLABELLED: Data from nine patients with leukemia participating in a phase I activity-escalation study of HuM195, labeled with the alpha-particle emitter 213Bi (half-life = 45.6 min), were used to estimate pharmacokinetics and dosimetry. This is the first trial using an alpha-particle emitter in humans. The linear energy transfer of alpha particles is several hundredfold greater than that of beta emissions. The range in tissue is approximately 60-90 microm. METHODS: The activity administered to patients ranged from 0.6 to 1.6 GBq. Patient imaging was initiated at the start of each injection. Thirty 1-min images followed by ten 3-min images were collected in dynamic mode; a 20% photopeak window centered at 440 keV was used. Blood samples were collected until 3 h postinjection and counted in a gamma counter. Contours around the liver and spleen were drawn on the anterior and posterior views and around a portion of the spine on the posterior views. No other organs were visualized. RESULTS: The percentage injected dose in the liver and spleen volumes increased rapidly over the first 10-15 min to a constant value for the remaining hour of imaging, yielding a very rapid uptake followed by a plateau in the antibody uptake curves. The kinetic curves were integrated to yield cumulated activity. The mean energy emitted per nuclear transition for 213Bi and its daughters, adjusted by a relative biologic effectiveness of 5 for alpha emissions, was multiplied by the cumulated activity to yield the absorbed dose equivalent. Photon dose to the total body was determined by calculating a photon-absorbed fraction. The absorbed dose equivalent to liver and spleen volumes ranged from 2.4 to 11.2 and 2.9 to 21.9 Sv, respectively. Marrow (or leukemia) mean dose ranged from 6.6 to 12.2 Sv. The total-body dose (photons only) ranged from 2.2 x 10(-4) to 5.8 x 10(-4) Gy. CONCLUSION: This study shows that patient imaging of 213Bi, an alpha-particle emitter, labeled to HuM195 is possible and may be used to derive pharmacokinetics and dosimetry. The absorbed dose ratio between marrow, liver and spleen volumes and the whole body for 213Bi-HuM195 is 1000-fold greater than that commonly observed with beta-emitting radionuclides used for radioimmunotherapy.

Acute Disease↗

PubMed1999

Thyroid cancer dosimetry using clearance fitting.

UNLABELLED: Since 1962, Memorial Sloan Kettering Cancer Center has used an individually optimized dosimetry method for patients with thyroid carcinoma undergoing radioiodine therapy. This traditional dosimetry method involves a determination of the maximum tolerated activity or the activity that will deliver 2 Gy to the blood (A(max)), and the corresponding ablative lesion dose (D(lesion)). However, the traditional calculations of A(max) and D(lesion) were based on empirical assumptions. The objective of this work was to develop a dosimetry method that eliminates these assumptions by incorporating patient kinetics and that is not restricted to 131I as a tracer and therapeutic agent. METHODS: Patient kinetics were incorporated into the dosimetry algorithm by fitting parameters to patient clearance measurements. The radioiodines 123I, 124I, 125I and 131I were accommodated as tracers and therapeutic agents by incorporating their physical half lives and by precalculating photon-absorbed fractions for these radionuclides for several thousand patient geometries using Monte Carlo simulations. RESULTS: A(max) and D(lesion) have been calculated using the traditional and new method for a group of patients, and errors associated with each of the above assumptions were examined. Assuming that the initial blood activity is distributed instantaneously in 5 L was found to introduce an error in A(max) of up to 30%, whereas assuming physical decay beyond the last data point introduced an error of up to 50%. CONCLUSION: Individualized fitting of clearance data is a practical method to accurately account for inter-patient kinetics variations. The substitution of standard kinetics beyond measured data might lead to substantial errors in estimating A(max) and D(lesion). In addition, gamma camera images, rather than neck probe readings, should be used to determine lesion uptakes for thyroid cancer patients.

Humans↗

PubMed1998

Use-dependent exacerbation of brain damage occurs during an early post-lesion vulnerable period.

For a period of time after unilateral brain injury, surviving neural tissue surrounding the lesion may be vulnerable to extremely high behavioral demand. Previously, we found that lesions of the forelimb representation area of the sensorimotor cortex (FL-SMC) in rats increase in size substantially when the intact forelimb is immobilized with a plaster of paris cast during the first 15 days after surgery, which forces overuse of the impaired forelimb. The present study was designed to determine whether the adult brain is more vulnerable to forced overuse of the impaired forelimb during the first 7 days post-lesion than during the second 7 days post-lesion. Using behavioral tests of forelimb use and stereological analysis of remaining tissue volume 40 days after FL-SMC lesions, we found that forced overuse of the impaired forelimb during the first 7 days after the initial damage caused expansion of neural injury and greatly interfered with restoration of function. In contrast, forced overuse of the impaired forelimb during the second 7 days had no significant effect on lesion size but nevertheless interfered with restoration of function. Thus, surviving neural tissue in the damaged hemisphere and recovery of function appear to be vulnerable to prolonged forced overuse of the impaired forelimb throughout the first 15 days, but tissue loss was detectable only when the animal was forced to use the impaired forelimb during the first 7 days after injury.

Animals↗