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K F Koral

Publications and source records attributed to K F Koral.

At least 19 recordsLinked to original sources
PubMed1995

A Monte Carlo investigation of dual-energy-window scatter correction for volume-of-interest quantification in 99Tcm SPECT.

Using Monte Carlo simulation of 99Tcm single-photon-emission computed tomography (SPECT), we investigate the effects of tissue-background activity, tumour location, patient size, uncertainty of energy windows, and definition of tumour region on the accuracy of quantification. The dual-energy-window method of correction for Compton scattering is employed and the multiplier which yields correct activity for the VI as a whole calculated. The model is usually a sphere containing radioactive water located within a cylinder filled with a more dilute solution of radioactivity. Two simulation codes are employed. Reconstruction is by ML-EM algorithm with attenuation compensation. The scatter multiplier depends only slightly on the sphere location or the cylinder diameter. It also depends little on whether correction is before or after reconstruction. At low background level, it changes with VOI size, but not at higher background. For a geometrical VOI, it is 1.25 at zero background, decreases sharply to 0.56 for equal concentrations, and is 0.44 when the background concentration is very large. Quantification is accurate (less than 9% error) if the test background is reasonably close to that used in setting the universal scatter-multiplier value, or if the test backgrounds are always large and so is the universal-value background, but not if the test backgrounds cover a large range of values including zero. Results largely agree with those from experiment after the experimental data with background is re-evaluated with prejudice.

Humans↗
PubMed1994

CT-SPECT fusion plus conjugate views for determining dosimetry in iodine-131-monoclonal antibody therapy of lymphoma patients.

UNLABELLED: A method for performing 131I quantitative SPECT imaging is described which uses the superimposition of markers placed on the skin to accomplish fusion of computed tomography (CT) and SPECT image sets. METHODS: To calculate mean absorbed dose after administration of one of two 131I-labeled monoclonal antibodies (Mabs), the shape of the time-activity curve is measured by daily diagnostic conjugate views, the y-axis of that curve is normalized by a quantitative SPECT measurement (usually intra-therapy), and the tumor mass is deduced from a concurrent CT volume measurement. The method is applied to six B-cell non-Hodgkin's lymphoma patients. RESULTS: For four tumors in three patients treated with the MB1 Mab, a correlation appears to be present between resulting mean absorbed dose and disease response. Including all dosimetric estimates for both antibodies, the range for the specific absorbed dose is within that found by others in treating B-cell lymphoma patients. Excluding a retreated anti-B1 patient, the tumor-specific absorbed dose during anti-B1 therapy is from 1.4 to 1.7 mGy/MBq. For the one anti-B1 patient, where quantitative SPECT and conjugate-view imaging was carried out back to back, the quantitative SPECT-measured activity was somewhat less for the spleen and much less for the tumor than that from conjugate views. CONCLUSION: The quantitative SPECT plus conjugate views method may be of general utility for macro-dosimetry of 131I therapies.

Adult↗
PubMed1993

Autoradiography-based, three-dimensional calculation of dose rate for murine, human-tumor xenografts.

A Fast Fourier Transform method for calculating the three-dimensional dose rate distribution for murine, human-tumor xenografts is outlined. The required input includes evenly-spaced activity slices which span the tumor. Numerical values in these slices are determined by quantitative 125I autoradiography. For the absorbed dose-rate calculation, we assume the activity from both 131I- and 90Y-labeled radiopharmaceuticals would be distributed as is measured with the 125I label. Two example cases are presented: an ovarian-carcinoma xenograft with an IgG 2ak monoclonal antibody and a neuroblastoma xenograft with meta-iodobenzylguanidine (MIBG). Considering all the volume elements in a tumor, we show, by comparison of histograms and also relative standard deviations, that the measured 125I activity and the calculated 131I dose-rate distributions, are similarly non-uniform and that they are more non-uniform than the calculated 90Y dose-rate distribution. However, the maximum-to-minimum ratio, another measure of non-uniformity, decreases by roughly an order of magnitude from one distribution to the next in the order given above.

Animals↗
PubMed1992

Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts.

We studied the effect of monoclonal antibody protein dose on the uniformity of radioiodinated antibody distribution within tumor masses using quantitative autoradiography. Groups (n = 11-13/group) of athymic nude mice with subcutaneous HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an 125I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4 using a high or a low protein dose (500 micrograms or 5 micrograms). At 6 days post-injection the macroscopic and microscopic intratumoral biodistribution of radiolabeled antibody was determined. The degree of heterogeneity of the labeled antibody distribution within each tumor was quantified and expressed as the coefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-micrograms protein doses had substantially lower CV values, 0.327 +/- 0.027, than did tumors from animals given 5-micrograms protein doses, 0.458 +/- 0.041, (P = 0.0078), indicating that the higher protein dose resulted in more homogeneous distribution of radioactivity in tumors than did the lower dose. While the percentage of the injected dose reaching the tumor was comparable between groups, injecting the higher dose of protein resulted in significantly lower tumor to non-tumor uptake ratios than those obtained for the lower protein dose. These data indicate, in this system, that to achieve more uniform intratumoral antibody (and radiation for radioimmunotherapy) delivery, a relatively high protein dose must be administered. However, to obtain this increased uniformity, a substantial drop in tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation of human tumor xenografts is a useful method to assess the intratumoral distribution of antibodies.

Adenocarcinoma↗
PubMed1992

Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma.

PURPOSE: This study was undertaken to evaluate the tumor targeting, toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell lymphoma patients who relapsed after chemotherapy. PATIENTS AND METHODS: Twelve patients with MB-1-reactive tumors were infused first with 40 mg of trace-labeled (3 to 7 mCi) MB-1. Ten patients who had no serious toxicity postinfusion and who had successful tumor imaging on serial gamma scans then received at least one 40-mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of delivered whole-body dose (WBD) were used in prescribing a millicurie RIT dose for seven patients. RESULTS: Eleven patients had positive tumor imaging after a tracer dose, including patients with bulky tumors and/or large tumor burdens (> or = 1 kg) +/- splenomegaly. However, overall sensitivity for the detection of known tumor sites was only 39%. In six of eight patients with dose-assessable tumors, the radiation dose to at least one tumor was 1.1 to 3.1 times higher than to any normal organ, excluding the spleen for a 40-mg tracer dose. Tracer-dose toxicities included reversible glossal edema in one patient, grade 3 hepatic transaminasemia in another, and early drops in both circulating B and T cells (with decreases in B cells more pronounced) in nearly all patients. RIT toxicity was primarily myelosuppression (especially thrombocytopenia), which had a delayed onset and protracted recovery (without significant recovery until at least 2 months post-RIT). Grade 3 myelosuppression in two of two patients who were treated at a tracer-projected 50-cGy WBD level (133 and 149 mCi) precluded further planned RIT dose escalation. Less myelosuppression was generally observed in patients who were treated at < or = 40-cGy WBD levels. Antimouse antibodies developed in two patients. Six patients had tumor responses post-RIT. Four had responses that lasted more than 1 month (2 to 6 months), which included one complete response, one partial response, one minor response, and one mixed response. Responses seemed to occur more frequently in imaged tumors than in nonimaged tumors. The most durable response occurred in a patient who had the best antibody targeting to tumor. CONCLUSIONS: Although 131I-MB-1 has limited diagnostic value, it can produce tumor responses at nonmarrow ablative RIT doses. Further studies that focus on improving tumor targeting with this or other B-cell-reactive radiolabeled antibodies and on ameliorating the myelosuppression associated with the RIT-dosing approach used in this trial are warranted.

Adult↗
PubMed1991

Importance of intra-therapy single-photon emission tomographic imaging in calculating tumour dosimetry for a lymphoma patient.

The dosimetry for two, similarly sized tumours in a lymphoma patient being treated with non-bone marrow ablative, monoclonal antibody therapy is reported. The 45-year-old man was infused with 2.48 GBq (67 mCi) of 131I-labelled MB-1. Prior to therapy, a time series of diagnostic conjugate-view images and a radionuclide transmission scan were obtained and processed to obtain time-activity curves. Starting 2 days after the therapeutic infusion of radioactivity, a second conjugate-view time series was obtained. At that time, a quantitative single-photon emission tomography (SPET) acquisition was also carried out. Pre- and post-therapy X-ray computed tomography scans demonstrated a percentage reduction in volume for the right tumour which was 3.8 times that for the left tumour. In contrast, diagnostic conjugate views by themselves estimated the absorbed dose to be the same for the two tumours. Addition of therapy conjugate-view data increased the right-over-left ratio but only to 1.22. Normalizing either time-activity series by the intra-therapy SPET results increased the ratio to greater than 1.5. We assume here that a differential dose is correct according to the differential tumour shirnkage. One can further assume that the largest ratio corresponds most certainly to the most accurate dosimetric method. Other assumptions are possible. While additional study is essential, data from this patient suggest that the preferred dosimetric method is intra-therapy SPET normalization of either time series.

Antibodies, Monoclonal↗
PubMed1991

Testing of local gamma-ray scatter fractions determined by spectral fitting.

The spectral-fitting method of correction for gamma-ray Compton scattering within objects separates the unscattered and scattered components of locally measured energy spectra. Here, we employ a third-order polynomial for the scattering and an approximately constant fitting window. A scatter fraction, defined as total scattered over total unscattered counts within a 20% window, is calculated for each point in our Anger camera images. These scatter fractions are tested against those from Monte-Carlo simulation for 99mTc and against results from semiconductor detector measurements for 131I. A radioactive sphere at several locations within a non-radioactive cylinder and the inverse are imaged for the testing. For one case, reproducibility of the spectral-fitting scatter fraction as a function of the number of unscattered counts within the 20% acceptance window was also determined. With 99mTc, for all cases, the agreement between spectral fitting and the standard estimation method is within 16%. With 131I, for the 'hot' sphere at two locations, the agreement is within 21%. For the 'hot' sphere at the third location (off the cylinder axis towards the camera), the dependence of scatter fraction on transverse distance is good although the absolute values are too large. Scatter fraction reproducibility is within 10% for 1000 or more counts. Therefore, further testing of spectral fitting and initial application to realistic clinical images seem to be in order.

Gamma Cameras↗
PubMed1990

SPECT dual-energy-window Compton correction: scatter multiplier required for quantification.

The dual-energy window Compton-scattering correction technique is defined here especially for accurate quantification of focal regions having higher than average uptake. The quantification is relative to a known-activity reference source. The scatter multiplier ("k" value) is determined for a radioactive 99mTc sphere on or off the axis of a cylinder containing water with or without background. Both maximum likelihood and filtered-backprojection reconstruction are employed. Either projections or tomograms are corrected. With tight regions of interest, there is a tendency for the requisite "k" value to be slightly lower as the diameter of the cylinder is increased. Neither sphere location nor background perturbs "k", however, so a constant value is a good, first approximation. Then a two-sphere validation test yields an accuracy of 8% with subtracted-tomograms ("k" = 1.30) and 2% with subtracted-projections ("k" = 1.20). With a reference-source region of interest which is four times larger, "k" is reduced and also now depends on background. Although equivalent quantitatively, maximum likelihood is preferable to filtered backprojection with Chang attenuation correction since it produces a less-noisy image.

Algorithms↗
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↗
PubMed1988

SPECT Compton-scattering correction by analysis of energy spectra.

The hypothesis that energy spectra at individual spatial locations in single photon emission computed tomographic projection images can be analyzed to separate the Compton-scattered component from the unscattered component is tested indirectly. An axially symmetric phantom consisting of a cylinder with a sphere is imaged with either the cylinder or the sphere containing 99mTc. An iterative peak-erosion algorithm and a fitting algorithm are given and employed to analyze the acquired spectra. Adequate separation into an unscattered component and a Compton-scattered component is judged on the basis of filtered-backprojection reconstruction of corrected projections. In the reconstructions, attenuation correction is based on the known geometry and the total attenuation cross section for water. An independent test of the accuracy of separation is not made. For both algorithms, reconstructed slices for the cold-sphere, hot-surround phantom have the correct shape as confirmed by simulation results that take into account the measured dependence of system resolution on depth. For the inverse phantom, a hot sphere in a cold surround, quantitative results with the fitting algorithm are accurate but with a particular number of iterations of the erosion algorithm are less good. (A greater number of iterations would improve the 26% error with the algorithm, however.) These preliminary results encourage us to believe that a method for correcting for Compton-scattering in a wide variety of objects can be found, thus helping to achieve quantitative SPECT.

Algorithms↗
PubMed1988

Conjugate view gamma camera method for estimating tumor uptake of iodine-131 metaiodobenzylguanidine.

Therapy with [131I]MIBG has produced partial remissions of malignant pheochromocytomas but not all patients respond. Responses correlate with the quantity of radiation delivered. We developed the conjugate-view method of imaging using 131I reference sources of known radioactivity placed on the surface of the patient and standard nuclear medicine equipment (gamma camera and computer), to estimate tumor uptake of [131I]MIBG. Such an estimate is a first step toward calculating radiation absorbed dose. Three different methods of background subtraction were evaluated with an anthropomorphic phantom and in five patients. In phantom results, measured tumor activity decreased exponentially with a half-life in agreement with that of 131I to within 3%. However, in the phantom studies, in which non-tumor activity is zero, no single method of background subtraction is superior. In patients, two background subtraction methods, which take their estimate from regions immediately surrounding or adjacent to the tumor and reference source, are less sensitive to reference source position and appear more accurate than a third method which uses a background region of interest displaced from the tumor. The agreement of the calculated activity concentration (nCi/g) with that measured by counting portions of the excised tumors gives validation to the method.

3-Iodobenzylguanidine↗
PubMed1986

Iodine-131 treatment of thyroid cancer: absorbed dose calculated from post-therapy scans.

The radiation absorbed dose for nine neck lesions distributed among four thyroid-cancer patients was measured directly from images taken after administration of a treatment dose of 131I. The tumor volume was measured with anterior plus lateral pinhole images by determining magnification and assuming an ellipsoidal shape. Uptake and effective half-life were determined from serial anterior images by use of a calibration curve. Dose lower limits ranged from 2,400 to 29,900 rad. Response to treatment was judged on the basis of one or more follow-up scans at least 8 mo later. All lesions responded to the therapy administration which ranged from 150 to 175 mCi.

Adenocarcinoma↗
PubMed1984

Performance evaluation of SPRINT, a single photon ring tomography for brain imaging.

SPRINT, a prototype single photon tomograph, has been designed primarily for high-resolution brain imaging in humans with I-123-labeled compounds such as iodoamphetamine, hydroxyiodopropyldiamine (HIPDM), and iodobenzene (IBZ). SPRINT uses a ring of stationary, discrete Nal detectors, and fan-beam sampling is accomplished with a rotating eight-slit aperture ring that acquires a complete projection set in 1/8 revolution. In-plane and cross-plane resolutions are 8mm and 10mm FWHM, respectively, measured on axis. Sensitivity with an 18% energy window is 1000 cprs per microCi/cc for Tc-99m in a 20 cm diameter phantom. A detailed evaluation of system performance has been completed, and preliminary human brain blood flow images have been obtained using HIPDM.

Brain↗