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  • 1
    Electronic Resource
    Electronic Resource
    Synthesis and Biological Evaluation of Radioiodinated Phospholipid Ether Stereoisomers (1995)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 38 (1995), S. 3156-3162 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00016a019
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  • 2
    Electronic Resource
    Electronic Resource
    Sulfhydryl site-specific crosslinking and labeling of monoclonal antibodies by a fluorescent equilibrium transfer alkylation crosslink reagent (1990)
    s.l. : American Chemical Society
    Bioconjugate chemistry 1 (1990), S. 51-59 
    Details
    ISSN: 1520-4812
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bc00001a006
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  • 3
    Electronic Resource
    Electronic Resource
    High-dose, unlabeled, nonspecific antibody pretreatment: influence on specific antibody localization to human melanoma xenografts (1987)
    Springer
    Cancer immunology immunotherapy 24 (1987), S. 221-224 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nonspecific uptake of radiolabeled monoclonal antibodies in normal tissues is a significant problem for tumor imaging. A potential means of decreasing nonspecific antibody binding is to “blockade” nonspecific antibody binding sites by predosing with cold, nonspecific isotypematched antibody, before injecting specific antibody. Nontumor-specific murine monoclonal antibody LK2H10 (IgG1) or Ab-1 (IgG2a) was given i.v. at doses of 0 to 3.5 mg to nude mice with xenografts of human melanoma. These mice were then given i.v. 4 μg of 131I anti-high molecular weight antigen of melanoma (HMWMAA) monoclonal antibody 763.24T (IgG1) or 225.28S (IgG2a), respectively. These mice were also given a tracer dose of 125I LK2H10 or Ab-1, respectively. Specific tumor uptake of anti-HMWMAA antibodies was see in all cases. No drop in tumor or nontumor uptake was demonstrated for either of the tumor-specific or nonspecific monoclonal antibodies due to nonspecific monoclonal antibody pretreatment. These data suggest that high doses of isotype-matched unlabeled nonspecific monoclonal antibody given before 131I tumor-specific monoclonal antibody, will not enhance tumor imaging.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205633
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  • 4
    Electronic Resource
    Electronic Resource
    Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts (1992)
    Springer
    Cancer immunology immunotherapy 35 (1992), S. 365-372 
    Details
    ISSN: 1432-0851
    Keywords: Monoclonal antibody ; Ovarian carcinoma ; Radiolabeled compounds ; Quantitative autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 an125I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4, using a high or a low protein dose (500 µg or 5 µg). 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 thecoefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-µg protein doses had substantially lower CV values, 0.327±0.027, than did tumors from animals given 5-µg 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01789014
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  • 5
    Electronic Resource
    Electronic Resource
    Investigations into the route of uptake and pharmacokinetics of intraperitoneally-administered monoclonal antibodies: I. Transdiaphragmatic blockade of the terminal lymphatics in the rat (1990)
    Springer
    Cancer immunology immunotherapy 31 (1990), S. 365-372 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies on the intraperitoneal administration of radiolabeled monoclonal antibodies indicate that the diaphragm and, in particular, the lymphatics associated with the diaphragm are more involved in the transport of such high-molecular-mass moieties than was earlier suspected. The current study examines the role of the diaphragm in the i.p. transport of an IgG2a murine monoclonal antibody, 5G6.4, by observing the effect on the absorption of the antibody produced when the diaphragm has been scarred. Normal, sham-operated, and diaphragmatically scarred (abrasions made with 600-grade sandpaper) female Sprague Dawley rats (150–250 g) were administered intraperitoneal injections of125labeled 5G6.4 in a volume of 2.0 cm3. Approximately 5 µg antibody protein was administered in the individual 19-µCi injections per rat. Scarring was effective in partially blocking the amount of labeled antibody that crossed the diaphragm. Mean diaphragm levels (% injected dose/g) of125I-labeled 5G6.4 from the scarred group were 16.8% lower than values from the sham-operated rats and 37.2% lower than those from the control rats. The blockade was effective in slowing the appearance of the labeled antibody in the systemic circulation. The half-time to absorption was significantly prolonged in the scarred group; meant1/2 absorption values of 2.5 h for the control group, 5.3 h for the shamoperated group, and 9.6 h for the diaphragmatically blocked group were recorded. Scarring the diaphragm reduced the mean maximum blood concentration by 27.6% over the control group and 23.9% over the sham-operated group. The mean time to maximum blood concentration was lengthened by 93.0% over the control group and 35.3% over the sham-operated group due as a result of scarification. Presumably this impedence to absorption would increase the time that the radiolabeled antibody bathed the peritoneal space. The scarred group also had the largest “system mean residence time” (162.5 h) compared to the sham-operated (147.9 h) and control (118.7 h) groups. These values further verify the effect of surgery on the kinetics of the i.p. administered radiolabeled monoclonals. This work demonstrates that scarifying the diaphragm does alter the kinetics of the i.p. administered monoclonal antibodies and supports the concept that transdiaphragmatic lymphatic absorption is an important route of antibody clearance from the peritoneal cavity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01741408
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  • 6
    Electronic Resource
    Electronic Resource
    The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage (1988)
    Springer
    Cancer immunology immunotherapy 26 (1988), S. 187-201 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The i.p. delivery of murine monoclonal antibody was compared with i.v. delivery in normal mice and rats, in normal nude mice and in those with i.p. human ovarian carcinoma xenografts. In normal rats, all classes of antibodies and antibody fragments evaluated were cleared from the peritoneal cavity at comparable rates. The regional delivery (Rd1) advantage to the peritoneal cavity following i.p. delivery was thus most dependent on the rate of clearance of the antibody or fragment from the blood stream. Determining the exact i.p. delivery advantage was problematic due to the difficulty in reliably obtaining peritoneal fluid later than 9–10 h after i.p. injection in normal animals. During the first 9 h following i.p. injection, the Rd(0–9/0–9) was, for a murine IgG2ak Fab〉F(ab′)2〉IgG (at 13.6〉10〉7.9). Two murine IgMs evaluated differed in Rd(0–9) at 27.1 and 9.2 respectively. When blood levels were extrapolated to infinity, these Rd (0–9/∞) values were considerably lower with the Fab having the highest Rd at 4.67. The i.p. Rd advantage was almost solely due to the i.p. antibody levels seen in the first 24 h after injection, as after that time, blood levels become comparable to those seen following i.v. injection. Normal tissues obtained at sacrifice 5–7 days after i.p. injection. Normal tissues obtained at sacrifice 5–7 days after i.p. or i.v. injection in rats showed comparable levels of radioantibody activity, whether the injection was i.p. or i.v. (except for higher diaphragmatic levels following i.p. delivery). In nude mice with i.p. human-derived ovarian tumors, intact IgG clearance from the peritoneal cavity to the blood was considerably slower than in normal animals, and early i.p. tumor uptake of specific antibody was significantly higher than that following i.v. antibody delivery. With higher early tumor uptake and lower systemic exposure, early tumor/nontumor ratios were significantly greater than those for i.v. delivery, though not beyond 48 h after i.p. injection. This study demonstrates the pharmacokinetic rationale for i.p. monoclonal antibody delivery, especially for agents cleared rapidly from the blood, such as antibody fragments. In addition, definite i.p. delivery benefit for antibody specific to i.p. tumors in the i.p. ovarian cancer system was shown soon after injection. These data regarding i.p. antibody delivery should be useful in rationally planning diagnostic and therapeutic studies involving the i.p. delivery of unmodified and immunoconjugated monoclonal antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199929
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  • 7
    Electronic Resource
    Electronic Resource
    Gastric xenon trapping mimicking COPD: Recognition using an effervescent agent (1986)
    Springer
    European journal of nuclear medicine 12 (1986), S. 155-157 
    Details
    ISSN: 1619-7089
    Keywords: Pulmonary embolism detection ; V/Q scanning ; Chronic obstructive lung disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Trapping of xenon 133 in the stomach due to gas swallowing can mimic xenon 133 retention in the left lower lobe due to obstructive lung disease on pulmonary ventilation/perfusion studies. In such cases, ingestion of sodium citrate-bicarbonate-simethicone crystals, which from CO2 gas on contact with water, can distend the xenoncontaining stomach and allow clear delineation of its gastric location. This approach is useful in selected cases and may help avoid false-positive diagnoses of obstructive airways disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00276710
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  • 8
    Electronic Resource
    Electronic Resource
    The (F)utility of the thallium-201 quantitative lung/myocardial ratio in the detection of coronary artery disease (1986)
    Springer
    European journal of nuclear medicine 12 (1986), S. 5-8 
    Details
    ISSN: 1619-7089
    Keywords: Thallium-201 ; Coronary artery disease ; Exercise testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exercise-induced increases in pulmonary uptake of thallium-201 (201Tl) have been associated with exercise-induced myocardial dysfunction. To evaluate this phenomenon more replicably, a quantitative semi-automated computer program was used to generate, from anterior exercise and delayed views, lung-myocardial ratios (LMR) of201Tl uptake in 78 patients [40 normal, 38 with coronary artery disease (CAD)]. Patients with CAD had a significantly higher mean exercise lung myocardial ratio (EXLMR) than normals (30.8 vs. 27.3;P 〈 0.003). In patients with adequate exercise (≥85% of an age-adjusted maximal heart rate), the EXLMRs of CAD patients were significantly higher than those of normals (29.7 vs. 25.5;P=0.003). However, this difference between CAD and normal patients was not apparent in a patient subgroup with submaximal exercise levels (〈 85% of an age-adjusted maximal heart rate). In both normal and CAD patients, EXLMR decreased with increasing exercise levels (r=-0.555;P=0.007). In patients with201Tl scans lacking visually defined perfusion defects (visually normal), an elevated LMR detected 60% of CAD cases with 81% specificity. A considerably elevated EXLMR in patients achieving adequate exercise should suggest the presence of CAD, even if there are no visually apparent cardiac perfusion defects. With submaximal exercise, however, the EXLMR is not a useful discriminator between CAD patients and normals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00638787
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  • 9
    Electronic Resource
    Electronic Resource
    Importance of intra-therapy single-photon emission tomographic imaging in calculating tumour dosimetry for a lymphoma patient (1991)
    Springer
    European journal of nuclear medicine 18 (1991), S. 432-435 
    Details
    ISSN: 1619-7089
    Keywords: Tumour dosimetry ; Single-photon emission tomography (SPET) quantification ; Lymphoma ; Monoclonal antibody ; Radionuclide therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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) of131I-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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02258433
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  • 10
    Electronic Resource
    Electronic Resource
    Tomographic renal cortical scintigraphy: Correlation with intravenous urography, computed tomography, ultrasonography, angiography, and nuclear magnetic resonance imaging (1985)
    Springer
    European journal of nuclear medicine 11 (1985), S. 217-220 
    Details
    ISSN: 1619-7089
    Keywords: Hypernephromas ; Renal cortex imaging ; Columns of Bertin ; Renal tumors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study evaluates single-photon renal tomoscintigraphy (SPECT) in the evaluation of renal masses and correlates this modality, where indicated, with computed tomography (CT), ultrasonography (US), angiography (ANGIO) and nuclear magnetic resonance imaging (NMR). Eight patients with renal cortical lesions detected on intravenous urography (IVP) were evaluated by SPECT and planar nuclear imaging using Tc-99m glucoheptonate (GH). Three of these patients were felt particularly likely to have renal tumors and were additionally evaluated with US, CT, ANGIO and NMR. The five patients with nodules on IVP that were not particularly suggestive of malignancy had functioning, benign, renal tissue accounting for their IVP lesions. Four of five were found by planar-GH nuclear imaging, five/five by SPECT-GH. In addition, SPECT-GH allowed better “confidence” in the normal renal tissue diagnosis in three/five cases. Of the three renal lesions that were highly suggestive of malignancy, two were hypernephromas and one was hypertrophied functioning cortical tissue. All three were correctly identified prospectively on SPECT-GH; however, one hypernephroma was missed on planar-GH. NMR, CT, and ANGIO detected only one of two hypernephromas prospectively (US detected both); all four modalities incorrectly diagnosed the hypertrophied tissue suggestive of malignancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279072
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