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K F Koral

Publications and source records attributed to K F Koral.

12 recordsLinked to original sources
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↗
PubMed1979

Application of ART to time-coded emission tomography.

Devices for single-photon emission tomography currently take projections either in a plane over a full angular range (0--360 degrees) or in a volume with a limited angular range. The planar, pseudo-random, time-coded aperture, in conjunction with an Anger camera, is a device of the limited angular range type. It employs multiple pinholes whose transmission varies as a function of time. Previously, image reconstruction was accomplished by simple back-projection of coefficients obtained by time-correlating pinhole transmission with detector-element count rate, resulting in a low-contrast image. Using the Algebraic Reconstruction Technique (ART) a method is introduced for division of the correlation coefficients into subsets allowing the three-dimensional reconstruction to be accomplished on a minicomputer. Results from simulations and experimental phantom data show that ART improves depth resolution compared to back-projection, that under-relaxation produces better images in the case of noisy data, and that the division of the correlation coefficients into subsets has no effect on quality. The images depict the expected resolution degradation in the direction normal to the detector plane due to the limited angular range of projections but yield quantitative results whose relative values are good, even though attenuation is neglected.

Mathematics↗
PubMed1979

Thyroid scintigraphy with time-coded aperture.

Coded aperture imaging (CAI) and multiple-view pinhole imaging (MVPI) of the thyroid were compared in 19 patients to determine whether CAI's theoretical advantages of high resolution, high efficiency, freedom from distortion, accurate size representation, and tomographic presentation could be realized in the clinical setting, and to determine whether CAI offers any advantage over conventional MVPI. The coded aperture images were judged better than the pinhole images in five cases, equal in 13 cases, and worse in one case. The major problem with CAI was the long reconstruction time. Further development and an extended clinical trial appear warranted.

Humans↗
PubMed1977

An operator-independent method for background subtraction in adrenal-uptake measurements: concise communication.

A new computer program for adrenal-uptake measurements is presented in which the algorithm identifies the adrenal and background regions automatically after being given a starting point in the image. Adrenal uptakes and results of reproducibility tests are given for patients injected with [131I] 6beta-iodomethyl-19-norcholesterol. The data to date indicate no overlap in the percent-of-dose uptakes for normal patients and patients with Cushing's disease and Cushing's syndrome.

Cholesterol↗
PubMed1975

Digital tomographic imaging with time-modulated pseudorandom coded aperture and Anger camera.

The properties of a time-modulated pseudorandom coded aperture with digital reconstruction are compared with those of conventional collimators used in gamma-ray imaging. The theory of this coded aperture is given and the signal-to-noise ratio in an element of the reconstructed image is shown to depend on the entire source distribution. Experimental results with a preliminary 4 X 4-cm pseudorandom coded aperture and an Anger camera are presented. These results include phantom and human thyroid images and tomographic images of a rat bone scan. The experimental realization of the theoretical advantages of the time-modulated coded aperture gives reason for continuing the clinical implementation and further development of the method.

Radionuclide Imaging↗
PubMedDate not supplied

Count-based monitoring of Anger-camera spectra--local energy shifts due to rotation.

This study reports on a spectral monitoring method in which (1) a small source fixed to the camera is used, (2) a narrow, offset window is set on the side of the photopeak, and (3) variations in count rate are measured to assess energy shifts in the vicinity of the source. For one camera model, the count rate drops from 100% to 76% over a rotation of 180 degrees, implying a local energy shift of 1.4 keV. Also looked for are local count-rate variations with rotation for (1) wide-symmetric, (2) 20%-symmetric, and (3) 10%-asymmetric windows. The last is in limited use to partially compensate for Compton scattering. The effects of background and time stability are assessed.

Gamma Cameras↗