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S M Larson

Publications and source records attributed to S M Larson.

At least 91 records · Page 5Linked to original sources
PubMed1997

Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding.

BACKGROUND: It is common protocol in radionuclide therapies to administer a tracer dose of a radiopharmaceutical, determine its lesion uptake and biodistribution by gamma imaging, and then use this information to determine the most effective therapeutic dose. This treatment planning approach can be used to quantitate accurately the activity and volume of lesions and organs with positron emission tomography (PET). In this article, the authors focus on the specification of appropriate volumes of interest (VoI) using PET in association with computed tomography (CT). METHODS: The authors have developed an automatic image segmentation schema to determine the VoI of metastases to the lung from PET images, under conditions of variable background activity. An elliptical Jaszczak phantom containing a set of spheres with volumes ranging from 0.4 to 5.5 mL was filled with F-18 activity (2-3 microCi/mL) corresponding to activities clinically observed in lung lesions. Images were acquired with a cold background and then with variable source-to-background (S/B) ratios of: 7.4, 5.5, 3.1, and 2.8. Lesion VoI analysis was performed on 10 patients with 17 primary or metastatic lung lesions, applying the optimum threshold values derived from the phantom experiments. Initial volume estimates for lung lesions were determined from CT images. Approximate S/B ratios were obtained for the corresponding lesions on F-18-fluoro-2-deoxy-D-glucose (18FDG)-PET images. From the CT estimate of the lesion size and the PET estimate of the S/B ratio, the appropriate optimum threshold could be chosen. The threshold was applied to the PET images to obtain lesion activity and a final estimate of the lesion volume. RESULTS: Phantom data analysis showed that image segmentation converged to a fixed threshold value (from 36% to 44%) for sphere volumes larger than 4 mL, with the exact value depending on the S/B ratios. For patients, the use of optimum threshold schema demonstrated a good correlation (r = 0.999) between the initial volume from CT and the final volume derived from the 18FDG-PET scan (P < 0.02). The mean difference for those volumes was 8.4%. CONCLUSIONS: The adaptive thresholding method applied to PET scans enables the definition of tumor VoI, which hopefully leads to accurate tumor dosimetry. This method can also be applied to small lesions (<4 mL). It should enable physicians to track objectively changes in disease status that could otherwise be obscured by the uncertainties in the region-of-interest drawing, even when the scans are delineated by the same physician.

Aged↗
PubMed1997

Thallium-201 scintigraphy for the evaluation of tumor response to preoperative chemotherapy in patients with osteosarcoma.

BACKGROUND: The degree of tumor necrosis after preoperative intravenous chemotherapy is likely to be an indicator of prognosis for patients with primary osteosarcoma. This study was undertaken to evaluate the efficacy of thallium-201 (Tl-201) scintigraphy in assessing response to chemotherapy in patients with osteosarcoma and to correlate the findings with the degree of tumor necrosis assessed histologically. METHODS: Twenty-four patients with biopsy-proven osteosarcoma underwent Tl-201 imaging before and immediately after preoperative intravenous chemotherapy. The maximum pixel counts taken over the tumor divided by those taken of a background region yielded a tumor-to-background ratio. The percentage of change in the tumor-to-background ratio before and after chemotherapy, defined as the alteration ratio, was correlated with the percentage of tumor necrosis. The percentages of tumor necrosis were classified into 4 grades: Grade 1, <50%; Grade 2, 50-89%; Grade 3, 90- 99%; Grade 4, 100%. RESULTS: Three patients with Grade 1 histologic response had an alteration ratio of 31% +/- 4 (mean +/- standard deviation). Three patients with Grade 2 response had an alteration ratio of 76% +/- 9. Nine patients with Grade 3 response had an alteration ratio of 84% +/- 11. Nine patients with Grade 4 response had an alteration ratio of 96% +/- 5. These ratios correlated well with the histologic grades (P < 0.001). CONCLUSIONS: The results of this study suggest that Tl-201 scintigraphy is a powerful tool in the evaluation of tumor response to chemotherapy in patients with osteosarcoma.

Adolescent↗
PubMed1997

Uptake and interconversion of the Z and E isomers of 17 alpha-iodovinyl-11 beta-methoxyestradiol in the immature female rat.

This study compares the specific uptake and retention of the Z and E isomers of 17 alpha-iodovinyl-11 beta-methoxyestradiol (IVME2) in estrogen target tissues in immature female rats following intraperitoneal injection. Estrogen receptor binding studies in vitro showed that the Z-IVME2 had greater affinity than the E-IVME2, but our initial in vivo data, comparing 125I-labeled E- or Z-IVME2 in separate studies showed no difference between the two isomers in either uptake or retention. These results were confirmed when the two isomers, labeled either with 123I or 125I, were injected simultaneously, allowing direct comparison of uptake and retention patterns in the same animal. Analysis of the nature of the radioiodinated estrogens in estrogen target tissues showed that at all time points, the estrogen target tissues contained mainly the E isomer, even at short times after injection of Z isomer. Although the Z-IVME2 was reasonably stable in the injectant, analysis of a peritoneal lavage soon after intraperitoneal injection of Z-[125I]-IVME2 showed that mainly the E isomer was present, suggesting that the conversion occurred prior to uptake by the tissues. In vitro studies with intraperitoneal fluid and serum showed that denaturing by heating at 65 degrees C substantially reduced their ability to affect the conversion of Z to E isomer, suggesting a possible enzymatic conversion.

Animals↗
PubMed1997

Midazolam changes cerebral blood flow in discrete brain regions: an H2(15)O positron emission tomography study.

BACKGROUND: Changes in regional cerebral blood flow (rCBF) determined with H2(15)O positron emission tomographic imaging can identify neural circuits affected by centrally acting drugs. METHODS: Fourteen volunteers received one of two midazolam infusions adjusted according to electroencephalographic response. Low or high midazolam effects were identified using post-hoc spectral analysis of the electroencephalographic response obtained during positron emission tomographic imaging based on the absence or presence of 14-Hz spindle activity. The absolute change in global CBF was calculated, and relative changes in rCBF were determined using statistical parametric mapping with localization to standard stereotactic coordinates. RESULTS: The low-effect group received 7.5 +/- 1.7 mg midazolam (serum concentrations, 74 +/- 24 ng/ml), and the high-effect group received 9.7 +/- 1.3 mg midazolam (serum concentrations, 129 +/- 48 ng/ml). Midazolam decreased global CBF by 12% from 39.2 +/- 4.1 to 34.4 +/- 6.1 ml x 100 g(-1) x min(-1) (P < 0.02 at a partial pressure of carbon dioxide of 40 mmHg). The rCBF changes in the low-effect group were a subset of the high-effect group. Decreased rCBF (P < 0.001) occurred in the insula, the cingulate gyrus, multiple areas in the prefrontal cortex, the thalamus, and parietal and temporal association areas. Asymmetric changes occurred, particularly in the low-effect group, and were more significant in the left frontal cortex and thalamus and the right insula. Relative rCBF was increased in the occipital areas. CONCLUSION: Midazolam causes dose-related changes in rCBF in brain regions associated with the normal functioning of arousal, attention, and memory.

Adult↗
PubMed1997

An investigation of the physical characteristics of 66Ga as an isotope for PET imaging and quantification.

Isotopes commonly used for PET imaging and quantification have a straightforward decay scheme involving "pure" positron (beta +) emission, i.e., 95%-100% beta + abundance, with no additional gamma rays. 66Ga (Emax = 4.2 MeV, T1/2 = 9.5 h) is a member of a category of isotopes with a lower abundance of beta +'s (57%) and a more complicated spectrum involving combinations of gamma rays that are emitted in cascade. These additional gamma rays tend to cause a higher singles rate, resulting in more random coincidence events. The most abundant positron (51.5%) in the spectrum has one of the highest energies considered for PET imaging. For the purpose of monoclonal antibody dosimetry using 66Ga, it is important to verify the quantification in phantoms prior to initiating human studies. A series of quantitative phantom measurements were performed on the PC4600, a head-optimized BGO based scanner with multiple detector rings. Count rate linearity was verified over concentrations ranging from 4.0 kBq/cc to 37 kBq/cc (0.11-1.0 microCi/cc); resolution averaged 16 mm full width half-maximum in the x and y directions in both the direct and cross planes. Axial resolution was 14 mm. The range of the energetic positrons (up to 4.153 MeV, range 7.6 mm in tissue) was verified as a primary source of resolution degradation. Within the limits outlined above, 66Ga is a suitable isotope for use as 66Ga citrate or with monoclonal antibodies in the detection and staging of tumors and other lesions. In addition, the energetic positrons have possible therapeutic applications when used as a monoclonal antibody label.

Beta Particles↗
PubMed1997

Implementation of a Monte Carlo dosimetry method for patient-specific internal emitter therapy.

In internal emitter therapy, an accurate description of the absorbed dose distribution is necessary to establish an administered dose-response relationship, as well as to avoid critical organ toxicity. This work describes the implementation of a dosimetry method that accounts for the radionuclide decay spectrum, and patient-specific activity and density distributions. The dosimetry algorithm is based on a Monte Carlo procedure that simulates photon and electron transport and scores energy depositions within the patient. The necessary input information may be obtained from a registered set of CT and SPECT or PET images. The algorithm provides the absorbed dose rate for the radioactivity distribution provided by the SPECT or PET image. The algorithm was benchmarked by reproducing dosimetric quantities using the Medical Internal Radionuclide Dose (MIRD) Committee's Standard Man phantom and was used to calculate absorbed dose distributions for representative case studies.

Humans↗
PubMed1997

Implementation and evaluation of patient-specific three-dimensional internal dosimetry.

UNLABELLED: Current methods for calculating the absorbed dose in a target region from a source region rely on a standard "reference man" geometry and assume an uniform distribution of radiolabel. While this approach is acceptable at the low levels of radioisotope administered for most diagnostic purposes, the generality of the calculations is not adequate for doses at the higher levels required for therapy and is not easily extendible to tumor dosimetry. METHODS: We have developed an integrated system which utilizes patient anatomy and radionuclide distribution in the calculation of absorbed dose rate or total dose to any user-defined target region. Images of radionuclide distribution (PET/SPECT) are registered to anatomic images (CT/ MRI) and then entered into a three-dimensional internal dosimetry software system (3D-ID) where regions of interest are defined. Dose calculations are performed by the mathematical convolution between a user-specified, dose-point kernel with the activity in the source volume over the target volume. The resulting dose rate distribution may be scaled by cumulated activity to yield absorbed dose. In addition to calculating the mean dose, dose-volume histograms may be generated which plot absorbed dose with respect to percent of volume. The method was evaluated using selected standard man phantom organs. RESULTS: Dose estimates for two patient studies are included to illustrate differences between patient-specific and MIRD-based calculations. The package provides an alternative approach to image display and three-dimensional internal dose calculations. CONCLUSION: The dose-volume histogram representation of absorbed dose to a target volume provides valuable information in assessing tumor control probability and normal tissue toxicity.

Dose-Response Relationship, Radiation↗
PubMed1997

Technetium-99m-MIBI versus fluorine-18-FDG in diffuse multiple myeloma.

Experience of scintigraphic detection of bone lesion and active bone marrow involvement of multiple myeloma, especially with sestamibi and FDG-PET scans is in evolution. We report a case of intense sestamibi uptake in bone marrow correlating with the extent of the disease, while FDG-PET scans showed activity only in areas of active disease progression associated with pain. Technetium-99m-sestamibi appears to indicate the extent of the disease, while [18F]FDG-PET scans show sites of active tumor proliferation and may be useful in directing local therapy such as radiation.

Aged↗
PubMed1997

Quantitative bone metastases analysis based on image segmentation.

UNLABELLED: Preliminary evidence indicates that the fraction of bone containing metastatic lesions is a strong prognostic indicator of survival longevity for prostate and breast cancer. Our current approach to quantify metastatic bone lesions, called the Bone Scan Index, is based on an inspection of the bone scan, estimating visually the fraction of each bone involved and then summing across all bones to determine the percentage of total skeletal involvement. This approach, however, is time consuming, subjective and dependent on individual interpretation. METHODS: To overcome these problems, a semiautomated image segmentation program was developed for the quantitation of metastases from planar whole-body bone scans. The user is required to insert a seed point into each metastatic region on the image. The algorithm then connects pixels to the seed pixel in all directions until a contrast-dependent threshold is reached. The optimal threshold for cessation of the region growing is determined from phantom studies. On the images, lesion delineation and size measurements were performed by the algorithm. Each delineated lesion is associated with a bone site using pull-down menus. The program then computes the fraction of lesion involvement in each bone based on look-up-tables containing the relationship of bone mass with race, sex, height and age. These look-up-tables were obtained by multiple regression of the skeletal mass measurements in humans. The total fraction of skeletal involvement is then obtained from the individual fractional masses. For individual fractional mass, values given in International Commission on Radiation Protection Publication No. 23 were used. RESULTS: The bone metastases analysis system has been used on 11 scans from 6 patients. The correlation was high (r = 0.83) between conventional (manually drawn region-of-interest) and this analysis system. Bone metastases analysis results in consistently lower estimates of fractional involvement in bone compared with the conventional region-of-interest drawing or visual estimation method. This is due to the apparent broadening of objects at and below the limits of resolution of the gamma camera. CONCLUSION: Image segmentation reduces the delineation and quantitation time of lesions by at least two compared with manual region-of-interest drawing. The objectivity of this technique allows the detection of small variations in follow-up patient scans for which the manual region-of-interest method may fail, due to performance variability of the user. This method preserves the diagnostic skills of the nuclear medicine physician to select which bony structures contain lesions, yet combines it with an objective delineation of the lesion.

Adolescent↗
PubMed1997

Jod-Basedow syndrome following oral iodine and radioiodinated-antibody administration.

This is a case of thyrotoxicosis, presumably due to Jod-Basedow syndrome, after stable iodine ingestion for thyroid blockade in a patient with ovarian carcinoma having 131I-labeled monoclonal antibody imaging. With the increased use of radioiodinated antibodies, for therapy and imaging, this possible side effect of excess stable iodine administration should be noted, especially in patients with pre-existing goiter.

Aged↗
PubMed1997

Distribution of radiolabeled monoclonal antibody MX35 F(ab')2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer.

Our objective was to quantify the targeting of the monoclonal antibody (mAb) MX35 F(ab')2 to micrometastatic epithelial ovarian cancer. This mAb detects a Mr 95,000 glycoprotein with homogeneous distribution on 80% of ovarian tumor specimens. Six patients with minimal residual disease from an imaging trial were injected with 2 or 10 mg of 131I- and 125I-labeled mAb MX35 F(ab')2. Biopsied samples were removed at second-look laparotomy 1-5 days post-i.v. or -i.p. infusion of antibody. Serial cryostat sections were stained by indirect immunoperoxidase method for antigen distribution and exposed to storage phosphor screens for quantitative autoradiography. Coregistration of tumor histology, antigen expression, and radionuclide distribution demonstrated specific localization in micrometastatic tumor foci (50 micrometer to 1 mm) found within tissue stroma. The radiolabeled antibody uptake determined by well scintillation counts ranged between 5.2 and 223.5 x 10(-4) percentage of injected dose/g of tumor tissue for 131I. Specific localization of mAb in tumor was determined by tumor:normal tissue (fat) ratios ranging from 0.9:1 to 35.9:1 for 131I. The high resolution and linear response of the storage phosphor screen imager was used to estimate the radionuclide activity localized in each micrometastatic site. Quantitation of phosphor screen response revealed microCi/g values of 0.026-0.341 for normal tissue and 0.184-6.092 for tumor biopsies, evaluated 4 or 5 days post-antibody injection. The tumor:normal tissue (adjacent to tumor) ratios were between 1 and 4 times greater using the phosphor screen method than well counter measurements, but even larger variations of ratios up to 20:1 were observed between tumor cell foci and stromal cells within the same tissue section. This study has demonstrated that mAb MX35 F(ab')2 localizes to the micrometastatic ovarian carcinoma deposits within the peritoneal cavity. The dosimetry results suggest a therapeutic potential for this antibody in patients with minimal residual disease (<5 mm).

Antibodies, Monoclonal↗
PubMed1996

Measurement of P-glycoprotein expression in multidrug-resistant human neuroblastoma cell lines using self-competitive binding assay.

To date, all reported measurements of multidrug resistance have been semiquantitative. The purpose of the present study is to establish and validate the self-competitive binding assay technique utilizing monoclonal antibody for quantitative estimation of multidrug resistance in tumor cells. This technique is used for P-glycoprotein concentration measurement in BE(2)-C human neuroblastoma cell line and its sublines with primary resistance to colchicine and actinomycin D. Monoclonal antibody MRK-16 was used in this study. It was labeled with iodine-125 (125I) to trace the concentration of antibody-antigen complexes. The binding data were obtained by varying the concentration of the unlabeled antibody. The results were fitted to a model equation to estimate the number of binding sites and antibody-antigen dissociation constant. The P-glycoprotein concentration was significantly higher in the resistant sublines than in the sensitive line. The highest levels were achieved in actinomycin D-resistant cells: 2.1 x 10(6) binding sites/cell versus 5.4 x 10(4) binding sites/cell in the sensitive cells. The consistency of the results was verified by repeating the study three times for each cell line. The binding assay results were confirmed by Western blot experiments performed on the same cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Targeting of small-cell lung cancer using the anti-GD2 ganglioside monoclonal antibody 3F8: a pilot trial.

The present study evaluated the ability of the anti-GD2 ganglioside monoclonal antibody 3F8 to target tumor sites in patients with small-cell lung cancer (SCLC). Of 12 patients entered into the trial, ten received intravenous 3F8 labeled with 2 or 10 mCi iodine-131. The first five patients had recurrent or progressive disease after chemotherapy. Subsequent patients were studied before starting chemotherapy. Radionuclide scans were performed on days 1, 2, and 3 post-infusion and once between day 5 and day 7. Four patients underwent single-photon emission tomography (SPET) imaging. Radionuclide scans demonstrated localization to all known sites of disease, other than small brain metastases in one patient. SPET/CT scan fusion images confirmed precise localization. No significant toxicity was observed. Mean serum half-life was 64.2 h. Analysis of specimens from one patient who died of unrelated causes 6 days post-infusion confirmed the scan results. The present study demonstrates that 3F8 targets SCLC sites in patients. Further studies of anti-GD2 antibodies with higher doses of antibody and radionuclide are warranted to evaluate their role in SCLC.

Carcinoma, Small Cell↗
PubMed1996

Comparison of the targeting characteristics of various radioimmunoconjugates for radioimmunotherapy of neuroblastoma: dosimetry calculations incorporating cross-organ beta doses.

To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.

Animals↗
PubMed1996

Detection of bony metastases of androgen-independent prostate cancer by PET-FDG.

Fourteen F-18 fluorodeoxyglucose (FDG) studies were carried out in 13 patients known to have bony metastases from carcinoma of the prostate. One patient was newly diagnosed. The remaining patients had various types of therapy and were considered hormonally resistant. The average age was 67. All patients had extensive bony metastases shown on the conventional Tc99m-MDP bone scans. Only about 18% of bony lesions apparent on the conventional bone scans showed corresponding increase of FDG uptake. Anatomical correlation was performed by using co-registered images of SPECT and PET in the same area. The positive FDG uptake was not related to the duration of illness, level of PSA, previous therapy, and magnitude of disease involvement. It appears that only a small percentage of bony metastases is associated with increased glycolysis. It is possible that other metabolic processes are more important than glycolysis for providing prostate cancer with a source of energy and nutrients.

Aged↗
PubMed1996

Phase I/II study of iodine 125-labeled monoclonal antibody A33 in patients with advanced colon cancer.

PURPOSE: A phase I/II study was designed to determine the maximum-tolerated dose (MTD) of iodine 125-labeled monoclonal antibody A33 (125I-mAb A33), its limiting organ toxicity, and the uptake and retention of radioactivity in tumor lesions. PATIENTS AND METHODS: Patients (N = 21) with advanced chemotherapy-resistant colon cancer who had not received prior radiotherapy were treated with a single 125I-mAb A33 dose. 125I doses were escalated from 50 to 350 mCi/m2 in 50-mCi/m2 increments. Radioimmunoscintigrams were performed for up to 6 weeks after 125I-mAb A33 administration. RESULTS: All 20 patients with radiologic evidence of disease showed localization of 125I to sites of disease. Twelve of 14 patients, who underwent imaging studies 4 to 6 weeks after antibody administration, had sufficient isotope retention in tumor lesions to make external imaging possible. No major toxicity was observed, except in one patient with prior exposure to mitomycin who developed transient grade 3 thrombocytopenia. Although the isotope showed variable uptake in the normal bowel, gastrointestinal symptoms were mild or absent, and in no case did stools become guaiac-positive. The MTD was not reached at 125I doses up to 350 mCi/m2. However, cytotoxicity assays demonstrated that patients treated with the highest dose had sufficiently high serum levels of 125I-mAb A33 to lyse colon cancer cells in vitro. Among 21 patients, carcinoembryonic antigen (CEA) levels returned to normal in one patient and decreased by 35% and 23%, respectively, in two patients; one additional patient had a mixed response on computed tomography. Additional, significant responses were observed in those patients treated with chemotherapy [carmustine [BCNU], vincristine, flourouracil, and streptozocin [BOF-Strep]) after completion of the 125I-mAb A33 study. CONCLUSION: Low-energy emission radioimmunotherapy with doses of up to 350 mCi/m2 of 125I-mAb A33 did not cause bowel or bone marrow toxicity. The modest antitumor activity in these heavily pretreated patients is encouraging because of lack of toxicity at the doses studied. The long radioactivity retention in tumors suggests that isotopes with a long half-life may have a therapeutic advantage, based on calculated dose delivery to tumor versus normal tissue. Due to the low bone marrow dose, further 125I trials with humanized mAb A33 are warranted, and controlled studies must be conducted to evaluate the combination of radioimmunotherapy and chemotherapy.

Adult↗