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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From the Departments of Medicine, Radiology, and
Medical Physics and the Molecular Pharmacology and Therapeutics
Program, Memorial Sloan-Kettering Cancer Center and the Weill
Medical College of Cornell University, New York, NY; the Radioimmune
and Inorganic Chemistry Section, Radiation Oncology Branch, National
Cancer Institute, National Institutes of Health, Bethesda, MD; and
the European Commission, Joint Research Center, Institute for
Transuranium Elements, Karlsruhe, Germany.
Unlike In the past decade, various approaches using native
monoclonal antibodies, immunotoxins, and radioimmunoconjugates have
emerged as promising strategies for the treatment of cancer,
particularly for hematologic malignancies.1-8 To date, all
clinical radioimmunotherapy studies have used HuM195 is a humanized anti-CD33 monoclonal antibody constructed by
grafting complementarity-determining regions of murine M195 into a
human IgG1 framework and backbone.17 The CD33 antigen is a
67-kd glycoprotein expressed on most myeloid leukemias and clonogenic
leukemia progenitors. It is also found on committed myelomonocytic and
erythroid progenitor cells, but not on mature granulocytes or
nonhematopoietic tissues.18-20 HuM195 displayed rapid
targeting of leukemia cells in patients and a pharmacology similar to
that of murine M195 but without significant
immunogenicity.21 Treatment with native HuM195 showed
activity against minimal residual disease in patients with acute
promyelocytic leukemia22 and produced rare complete
remissions in patients with relapsed or refractory myeloid
leukemia.23,24 When labeled with therapeutic doses of the
213Bi has a half-life of 45.6 minutes and emits an HuM195-CHX-A-DTPA
Isotope preparation and radiolabeling
Study design Patients with relapsed or refractory acute myelogenous leukemia (AML), accelerated phase or myeloid blast crisis of chronic myelogenous leukemia, or chronic myelomonocytic leukemia (CMMOL) were eligible if more than 25% of their bone marrow blasts expressed CD33. Patients did not receive any antileukemic therapy for 3 weeks before entering the study except for hydroxyurea, which was permitted to control peripheral blood leukocyte counts. Concurrent use of either oral or intravenous antibiotics was allowed. Entry criteria included serum creatinine level less than 1.5 times normal, serum bilirubin of 1.5 mg/dL or less, and hepatic transaminases and alkaline phosphatase 2.5 times normal or less. Patients could not have detectable antibodies to HuM195 or active central nervous system involvement by leukemia.213Bi-HuM195 was given as a 5-minute infusion, 2 to 4 times
daily in 148 to 925 MBq fractions over 2 to 4 days. Because
213Bi yields were limited by the activity of each
225Ac/213Bi generator and because of
constraints on the specific activity that could be achieved for any one
injection, we escalated radioactivity doses by increasing the number of
injections. Patients received a total of 3 to 7 injections. Five dose
levels of 213Bi-HuM195 were administered Biodistribution The emissions of 213Bi allowed biodistribution,
pharmacokinetic, and dosimetry studies to be performed as previously
described.39 Patient images were obtained after at least
the first or last dose of 213Bi-HuM195 on a dual-head
Vertex gamma camera (ADAC Laboratories, Milpitas, CA). Imaging began at
the start of injection. Using a 20% photopeak window centered at 440 keV, the energy emitted in the   decay of
213Bi, we collected 30 1-minute images followed by 10 3-minute images in dynamic mode. Contours around the liver, spleen, and
vertebrae were used to determine the number of counts in these regions
at each time point. We calculated the activities in the liver and spleen as the geometric mean of the counts per minute in the anterior and posterior images. Activity in the spine was estimated from the
posterior view only. Kinetic curves were generated, corrected for
decay, and converted to percentage injected dose (%ID) for each
region. The %ID for the spine was converted to marrow %ID by scaling
a nominal estimate of the red marrow mass in the vertebrae according to
body weight.39
Pharmacokinetics Blood samples were collected at 5, 10, 15, 30, 45, 60, 90, 120, and 180 minutes following the first or last injection, or both, of 213Bi-HuM195 in conjunction with gamma camera imaging. Aliquots of whole blood and plasma were analyzed for 1 minute in a gamma counter (Compugamma model 1282; LKB Wallac, Gaithersburg, MD). The data were decay corrected to the time of injection and expressed as percentage of injected activity per liter.39Dosimetry We used a conventional medical internal radiation dose approach to estimate the average radiation doses delivered to specific organs.40 Time-activity data were fitted to a sum or difference of 2 exponential expressions, and these expressions were integrated to determine the cumulated activity within each region or organ. Organ volumes were estimated using previously described methods39 and were converted to masses assuming unit density. The cumulated activity for each volume, Ã, was divided by the mass of each organ (MORG) to give cumulated activity concentration. Mean absorbed doses to liver, spleen, and red marrow were obtained by multiplying the cumulated activity concentration in each organ by the mean energy emitted per nuclear transition, , for the electron and  particle emissions of
213Bi and its daughters 213Po,
209Tl, and 209Pb. Relative biologic
effectiveness of 5 for cellular inactivation was assumed for particles.41 The absorbed dose over an organ volume,
DORG, is given by the equation:
e + 5 ). In most patients, pharmacokinetic data were
collected only after the first and last injections. If no data were
collected during injections, we calculated absorbed doses or dose
equivalents by weighted averaging of the image-derived values. The
weight assigned to known values depended on the number of injections
elapsed between 2 estimates. Known values that were closer in injection
number to the unknown value were given greater weight.
Patient characteristics We treated 18 patients in the study. Fourteen patients had relapsed AML, and 3 had primary refractory AML and did not achieve complete remission after 2 or more induction courses. One patient had relapsed CMMOL (Table 1). The median age was 56 years (range, 17 to 74 years), and the median number of prior treatments was 3 (range, 2 to 9). Four patients previously underwent allogeneic (n = 2) or autologous (n = 2) bone marrow or peripheral blood progenitor cell transplantation.
Adverse effects Treatment with 213Bi-HuM195 was well tolerated. Maximum tolerated dose in this study was not reached because escalation beyond 37 MBq/kg was restricted by the availability and cost of 225Ac. Because only 0.3 to 1 mg HuM195 was administered in each dose fraction, no infusion-related toxicity was seen. Grade 1 1iver function abnormalities were seen in 4 patients (22%). Two of these patients had elevations in alkaline phosphatase levels; one had hyperbilirubinemia, and one had an elevated transaminase level. Two patients (11%) had grade 2 hyperbilirubinemia. There was no correlation between administered activity and the occurrence of these abnormalities (r = 0.051; P = .841). The onset was typically 5 to 14 days following treatment, and these abnormalities resolved within 3 to 14 days.Myelosuppression, demonstrated by a decline in the number of normal peripheral white blood cells or blasts, was seen in all 17 evaluable patients. Thirteen (76%) of the 17 patients developed grade 3 (n = 2) or 4 (n = 11) leukopenia; however, substantial clearing of circulating blasts (more than 95%) accounted for this finding in 11 patients (85%). Decreases in normal leukocyte counts could be explained by the destruction of myeloid progenitors that express CD33 and by the nonspecific irradiation of normal blood elements. Median time from initiation of treatment to resolution of grade 3 or 4 leukopenia was 22 days (range, 12-41 days). Dose-limiting toxicity, defined as grade 4 leukopenia for more than 35 days from the start of therapy, was seen in one patient treated at the 37 MBq/kg dose level following relapse after allogeneic BMT. The duration of myelosuppression was unrelated to the level of CD33 expression (r = 0.119; P = .648), the number of previous treatments (r = 0.207; P = .426), or the administered activity (r = 0.390; P = .121). Because pancytopenia is a prominent clinical feature of leukemia, we could not evaluate other hematologic toxicities in most patients. Among the 6 patients who had an absolute neutrophil count (ANC) of 1.5 × 109/L or more before receiving 213Bi-HuM195, 4 (66%) developed grade 4 neutropenia (ANC less than 0.5 × 109/L). Eight (44%) of the 18 patients were hospitalized for neutropenic fever. Of the 2 patients who had platelet counts greater than 50 × 109/L before treatment, one required transfusions for a platelet count of less than 10 × 109/L following therapy. Biodistribution Gamma camera imaging showed localization of 213Bi to expected areas of leukemic involvement, including the bone marrow of the vertebrae and pelvis, the liver, and the spleen in all patients (Figure 1). Despite avidity for free bismuth, the kidneys were not visualized. This suggested that no significant catabolism or clearance of the drug occurred, thereby confirming the stability of the construct in vivo. Uptake by the marrow, liver, and spleen, accounting for 70% to 100% of the administered activity, occurred within 5 to 10 minutes after injection and was maintained throughout the 1-hour period of image collection (Figure 2).
Sixteen patients underwent gamma camera imaging after at least 2 injections of 213Bi-HuM195 during the treatment course. The pattern of uptake within the bone marrow was variable. Six patients (38%) demonstrated an increase in marrow activity with greater numbers of injections. Five patients (31%) showed a decrease, and activity remained constant in 5 patients (31%). The effect of multiple doses on biodistribution within the liver and spleen was more consistent. Twelve (75%) of the 16 patients had a decrease in liver activity with increasing numbers of injections. Two patients (12.5%) had an increase in liver activity, and the activity was constant in the remaining 2 patients (12.5%). Similarly, 9 patients (56%) had a decrease in activity within the spleen after multiple injections; 1 patient (6%) had an increase, and 6 patients (38%) had no change. This tendency toward decreased liver and spleen uptake after multiple injections of 213Bi-HuM195 suggested a CD33 antigen saturation effect at these sites after the administration of several milligrams of antibody. Pharmacokinetics Blood and plasma antibody concentrations displayed typical distributions over the first 20 to 40 minutes, followed by slower clearance over the remaining 3 hours of sample collection (Figure 3). Additionally, we found that clearance
rates were independent of the number of injections. Estimated initial
distribution volumes in blood and plasma were similar for all patients,
indicating that a significant fraction of activity in the blood was
associated with cellular elements. Among the 15 patients for whom
pharmacokinetic studies were performed after at least 2 injections, 13 (87%) had higher activity concentrations in blood or plasma following
later injections. This suggested that increasing levels of antigen
saturation at sites within the bone marrow, liver, and spleen occurred
after multiple injections of 213Bi-HuM195.
Dosimetry Mean ± standard deviation absorbed dose per amount of injected activity to the marrow was 9.8 ± 6.5 mSv/MBq (range, 2.6-29.4 mSv/MBq). Mean absorbed doses per injected activity for the liver, spleen, and blood were 5.8 ± 1.6 mSv/MBq (range, 3.9-9.7 mSv/MBq), 10.8 ± 5.4 mSv/MBq (range, 3.8-24.2 mSv/MBq), and 2.6 ± 1.2 mSv/MBq (range, 1-5.1 mSv/MBq), respectively. Estimated total dose equivalents to the marrow, and therefore to CD33+ target cells, ranged from 6.6 to 73 Sv. Total dose equivalents to the liver, spleen, and blood ranged from 2.4 to 23.5 Sv, 2.9 to 36.8 Sv, and 1.1 to 11 Sv, respectively (Figure 4). As expected, we found linear correlations between the total injected activity and total dose equivalents to the liver (r = 0.764; P < .001), spleen (r = 0.754; P < .001), and blood (r = 0.608; P = .007). Additionally, there was a strong trend toward a positive correlation between injected activity and dose equivalents delivered to the marrow (r = 0.456; P = .057).
Because of the short range of the Antileukemic effects Fifteen of 18 patients had leukemic blasts in the peripheral blood before treatment with 213Bi-HuM195. Fourteen (93%) of these 15 patients had reductions in circulating blasts following therapy (Figure 5A). Mean ± standard deviation percentage reduction in circulating blasts for these 14 patients was 90% ± 21%, (median, 98.5%; range, 34%-100%). Even at the lowest dose level, 2 of the 3 patients had elimination of more than 99% of peripheral blasts. Up to 3 logs of circulating leukemia cells were killed, and 4 patients (27%) had complete eradication of peripheral leukemia cells. Circulating blast counts decreased rapidly, with nadirs occurring after a median of 10 days (range, 4-17 days). Suppression of peripheral blast counts lasted a median of 19 days (range, 8-42 days).
Fourteen (78%) of the 18 patients had reductions in the percentages of bone marrow leukemia cells 7 to 10 days after treatment (Figure 5B). We did not find a clear correlation between the degree of elimination of blasts in the peripheral blood and bone marrow (r = 0.454; P = .089), likely because 213Bi-HuM195 rapidly targeted and cleared circulating blasts before reaching leukemia cells within the marrow. Among the 4 patients with complete elimination of peripheral blood blasts, 3 had reductions in bone marrow blasts. The percentage reduction of marrow blasts and the level of CD33 expression were also unrelated (r = 0.074; P = .769). Reductions in bone marrow blasts, however, occurred more consistently with higher injected activities. Only 4 (44%) of the first 9 patients had partial responses with at least a 25% decrease in the percentage of bone marrow blasts, whereas 8 (89%) of the last 9 patients had partial responses (P = .046). Across all dose levels, the mean percentage reduction in bone marrow blasts for the 14 responders was 41% ± 22% (median, 41%; range, 8%-79%). Although 213Bi-HuM195 produced significant antileukemic effects accounting for hundreds of billions of selectively killed cells, no complete remissions were observed.
This is the first study to show the proof-of-concept for Although myelosuppression was seen in all evaluable patients, treatment with 213Bi-HuM195 produced no significant extramedullary toxicity. The drug rapidly cleared from the blood to expected areas of leukemic involvement, including the bone marrow, liver, and spleen, within 5 to 10 minutes of injection. No uptake by any other organ was seen. Of the 16 patients who were studied, 12 (75%) showed decreased activity in the liver after multiple injections of 213Bi-HuM195, and 9 (56%) had decreased activity in the spleen. This is likely because of first-pass binding to leukemia cells and CD33+ monocytes at these sites. The pattern of biodistribution in the marrow after multiple injections was variable, with 6 patients (38%) showing an increase in activity, 5 (31%) showing a decrease, and 5 (31%) showing no change. This variability, likely because of differences in tumor burden and first-pass binding, explains the lack of correlation between the duration of myelosuppression and administered activity. The dosimetry of Although leukemia is characterized predominantly by the unregulated
growth of blasts within the bone marrow, extramedullary involvement of
the liver and spleen is common. Therefore, most CD33+
target cells reside in these 3 sites. Dose equivalents up to 73 Sv,
23.5 Sv, and 36.8 Sv were delivered to the marrow, liver, and spleen,
respectively. Calculated absorbed doses to each of these organ volumes,
however, may not reflect the actual dose to individual target cells or
to normal organ parenchymal cells. Because of the short range of Our previous studies with
131I-M195,25,44
131I-HuM195,21 and
90Y-HuM19526 allowed us to compare the
dosimetry of
213Bi-HuM195 displayed clear antileukemic activity. Fourteen (93%) of 15 evaluable patients had reductions in peripheral blood leukemia cells, and 14 (78%) of the 18 patients had reductions in the percentages of bone marrow blasts. There was a predictable increase in the absorbed dose to target organs when higher activities of 213Bi-HuM195 were administered. Accordingly, reductions in bone marrow blasts occurred more consistently at higher dose levels. Observation of a clear dose-response effect over all dose levels, however, was confounded by the small number of patients who displayed a wide variability in tumor burden, target antigen expression, and tumor cell radiation resistance, in part because of previous treatment. Although 213Bi-HuM195 killed large leukemic volumes in many
patients, none achieved complete remission. Because of the nature of
The current study provides proof-of-concept for the use of
We thank Peter G. Maslak and Ellin Berman for clinical care;
Bipin M. Mehta, Michael Curcio, Yan Ma, Jing Qiao, and Lawrence Lai for
laboratory assistance; Jenny Jimenez for assistance with data
management; Lucy Dantis and her staff for expert research nursing
(Memorial Sloan-Kettering Cancer Center, New York, NY); Chuanchu Wu for
assistance in preparing the HuM195 immunoconjugate (Radioimmune and
Inorganic Chemistry Section, National Cancer Institute, Bethesda, MD);
Sead Mirzadeh (Oak Ridge National Laboratory, TN), Christos Apostolidis
(Institute for Transuranium Elements, Karlsruhe, Germany), Maurits
Geerlings, Sr (Pharmactinium, Alexandria, VA) for supplying
225Ac, and Daniel Levitt (Protein Design Labs, Fremont, CA)
for supplying HuM195. We dedicate this work to the memory of Otto
Gansow, who was instrumental in the development of chelating agents for
Submitted October 9, 2001; accepted April 9, 2002.
Supported by National Institutes of Health grants PO1 CA33049 and RO1 CA55349. J.G.J. is a recipient of a Clinical Oncology Career Development Award from the American Cancer Society. D.A.S. is a Translational Investigator of the Leukemia Society of America and a Doris Duke Distinguished Clinical Scientist.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Joseph G. Jurcic, Memorial Sloan-Kettering Cancer Center, Box 458, 1275 York Ave, New York, NY 10021; e-mail: jurcicj{at}mskcc.org.
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J. M. Pagel, A. Pantelias, N. Hedin, S. Wilbur, L. Saganic, Y. Lin, D. Axworthy, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, et al. Evaluation of CD20, CD22, and HLA-DR Targeting for Radioimmunotherapy of B-Cell Lymphomas Cancer Res., June 15, 2007; 67(12): 5921 - 5928. [Abstract] [Full Text] [PDF]
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 M. Zhang, Z. Yao, H. Patel, K. Garmestani, Z. Zhang, V. S. Talanov, P. S. Plascjak, C. K. Goldman, J. E. Janik, M. W. Brechbiel, et al. Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1 PNAS, May 15, 2007; 104(20): 8444 - 8448. [Abstract] [Full Text] [PDF]
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C. Friesen, G. Glatting, B. Koop, K. Schwarz, A. Morgenstern, C. Apostolidis, K.-M. Debatin, and S. N. Reske Breaking Chemoresistance and Radioresistance with [213Bi]anti-CD45 Antibodies in Leukemia Cells Cancer Res., March 1, 2007; 67(5): 1950 - 1958. [Abstract] [Full Text] [PDF]
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T. K. Stutchbury, F. Al-ejeh, G. E. Stillfried, D. R. Croucher, J. Andrews, D. Irving, M. Links, and M. Ranson Preclinical evaluation of 213Bi-labeled plasminogen activator inhibitor type 2 in an orthotopic murine xenogenic model of human breast carcinoma Mol. Cancer Ther., January 1, 2007; 6(1): 203 - 212. [Abstract] [Full Text] [PDF]
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M. Zhang, Z. Yao, Z. Zhang, K. Garmestani, V. S. Talanov, P. S. Plascjak, S. Yu, H.-S. Kim, C. K. Goldman, C. H. Paik, et al. The Anti-CD25 Monoclonal Antibody 7G7/B6, Armed with the {alpha}-Emitter 211At, Provides Effective Radioimmunotherapy for a Murine Model of Leukemia Cancer Res., August 15, 2006; 66(16): 8227 - 8232. [Abstract] [Full Text] [PDF]
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G. Glatting, M. Muller, B. Koop, K. Hohl, C. Friesen, B. Neumaier, E. Berrie, P. Bird, G. Hale, N. M. Blumstein, et al. Anti-CD45 Monoclonal Antibody YAML568: A Promising Radioimmunoconjugate for Targeted Therapy of Acute Leukemia J. Nucl. Med., August 1, 2006; 47(8): 1335 - 1341. [Abstract] [Full Text] [PDF]
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J. M. Pagel, F. R. Appelbaum, J. F. Eary, J. Rajendran, D. R. Fisher, T. Gooley, K. Ruffner, E. Nemecek, E. Sickle, L. Durack, et al. 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission Blood, March 1, 2006; 107(5): 2184 - 2191. [Abstract] [Full Text] [PDF]
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D. C. Taussig, D. J. Pearce, C. Simpson, A. Z. Rohatiner, T. A. Lister, G. Kelly, J. L. Luongo, G.-a. H. Danet-Desnoyers, and D. Bonnet Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia Blood, December 15, 2005; 106(13): 4086 - 4092. [Abstract] [Full Text] [PDF]
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T. Back, H. Andersson, C. R. Divgi, R. Hultborn, H. Jensen, S. Lindegren, S. Palm, and L. Jacobsson 211At Radioimmunotherapy of Subcutaneous Human Ovarian Cancer Xenografts: Evaluation of Relative Biologic Effectiveness of an {alpha}-Emitter In Vivo J. Nucl. Med., December 1, 2005; 46(12): 2061 - 2067. [Abstract] [Full Text] [PDF]
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G. J. Kelloff, K. A. Krohn, S. M. Larson, R. Weissleder, D. A. Mankoff, J. M. Hoffman, J. M. Link, K. Z. Guyton, W. C. Eckelman, H. I. Scher, et al. The Progress and Promise of Molecular Imaging Probes in Oncologic Drug Development Clin. Cancer Res., November 15, 2005; 11(22): 7967 - 7985. [Abstract] [Full Text] [PDF]
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S. Supiot, S. Gouard, J. Charrier, C. Apostolidis, J.-F. Chatal, J. Barbet, F. Davodeau, and M. Cherel Mechanisms of Cell Sensitization to {alpha} Radioimmunotherapy by Doxorubicin or Paclitaxel in Multiple Myeloma Cell Lines Clin. Cancer Res., October 1, 2005; 11(19): 7047s - 7052s. [Abstract] [Full Text] [PDF]
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O. R. Pozzi and M. R. Zalutsky Radiopharmaceutical Chemistry of Targeted Radiotherapeutics, Part 2: Radiolytic Effects of 211At {alpha}-Particles Influence N-Succinimidyl 3-211At-Astatobenzoate Synthesis J. Nucl. Med., August 1, 2005; 46(8): 1393 - 1400. [Abstract] [Full Text] [PDF]
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Y. Miao, M. Hylarides, D. R. Fisher, T. Shelton, H. Moore, D. W. Wester, A. R. Fritzberg, C. T. Winkelmann, T. Hoffman, and T. P. Quinn Melanoma Therapy via Peptide-Targeted {alpha}-Radiation Clin. Cancer Res., August 1, 2005; 11(15): 5616 - 5621. [Abstract] [Full Text] [PDF]
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S. Nilsson, R. H. Larsen, S. D. Fossa, L. Balteskard, K. W. Borch, J.-E. Westlin, G. Salberg, and O. S. Bruland First Clinical Experience with {alpha}-Emitting Radium-223 in the Treatment of Skeletal Metastases Clin. Cancer Res., June 15, 2005; 11(12): 4451 - 4459. [Abstract] [Full Text] [PDF]
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J. Singh Jaggi, B. J. Kappel, M. R. McDevitt, G. Sgouros, C. D. Flombaum, C. Cabassa, and D. A. Scheinberg Efforts to Control the Errant Products of a Targeted In vivo Generator Cancer Res., June 1, 2005; 65(11): 4888 - 4895. [Abstract] [Full Text] [PDF]
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J. Elgqvist, P. Bernhardt, R. Hultborn, H. Jensen, B. Karlsson, S. Lindegren, E. Warnhammar, and L. Jacobsson Myelotoxicity and RBE of 211At-Conjugated Monoclonal Antibodies Compared with 99mTc-Conjugated Monoclonal Antibodies and 60Co Irradiation in Nude Mice J. Nucl. Med., March 1, 2005; 46(3): 464 - 471. [Abstract] [Full Text] [PDF]
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R. M. Sharkey and D. M. Goldenberg Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies J. Nucl. Med., January 1, 2005; 46(1_suppl): 115S - 127S. [Abstract] [Full Text] [PDF]
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D. A. Mulford, D. A. Scheinberg, and J. G. Jurcic The Promise of Targeted {alpha}-Particle Therapy J. Nucl. Med., January 1, 2005; 46(1_suppl): 199S - 204S. [Abstract] [Full Text] [PDF]
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D. E. Milenic, K. Garmestani, E. D. Brady, P. S. Albert, D. Ma, A. Abdulla, and M. W. Brechbiel Targeting of HER2 Antigen for the Treatment of Disseminated Peritoneal Disease Clin. Cancer Res., December 1, 2004; 10(23): 7834 - 7841. [Abstract] [Full Text] [PDF]
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A. M. Ballangrud, W.-H. Yang, S. Palm, R. Enmon, P. E. Borchardt, V. A. Pellegrini, M. R. McDevitt, D. A. Scheinberg, and G. Sgouros Alpha-Particle Emitting Atomic Generator (Actinium-225)-Labeled Trastuzumab (Herceptin) Targeting of Breast Cancer Spheroids: Efficacy versus HER2/neu Expression Clin. Cancer Res., July 1, 2004; 10(13): 4489 - 4497. [Abstract] [Full Text] [PDF]
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S. Sofou, J. L. Thomas, H.-y. Lin, M. R. McDevitt, D. A. Scheinberg, and G. Sgouros Engineered Liposomes for Potential {alpha}-Particle Therapy of Metastatic Cancer J. Nucl. Med., February 1, 2004; 45(2): 253 - 260. [Abstract] [Full Text] [PDF]
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M. Miederer, M. R. McDevitt, G. Sgouros, K. Kramer, N.-K. V. Cheung, and D. A. Scheinberg Pharmacokinetics, Dosimetry, and Toxicity of the Targetable Atomic Generator, 225Ac-HuM195, in Nonhuman Primates J. Nucl. Med., January 1, 2004; 45(1): 129 - 137. [Abstract] [Full Text] [PDF]
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R. Huber, C. Seidl, E. Schmid, S. Seidenschwang, K.-F. Becker, C. Schuhmacher, C. Apostolidis, T. Nikula, E. Kremmer, M. Schwaiger, et al. Locoregional {alpha}-Radioimmunotherapy of Intraperitoneal Tumor Cell Dissemination Using a Tumor-specific Monoclonal Antibody Clin. Cancer Res., September 1, 2003; 9(10): 3922S - 3928. [Abstract] [Full Text] [PDF]
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W. A. Bethge, D. S. Wilbur, R. Storb, D. K. Hamlin, E. B. Santos, M. W. Brechbiel, D. R. Fisher, and B. M. Sandmaier Selective T-cell ablation with bismuth-213-labeled anti-TCR{alpha}{beta} as nonmyeloablative conditioning for allogeneic canine marrow transplantation Blood, June 15, 2003; 101(12): 5068 - 5075. [Abstract] [Full Text] [PDF]
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| Copyright © 2002 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
particle immunotherapy for myeloid leukemia
Top
Abstract
Introduction
10.36, 15.54, 20.72, 25.9, and 37 MBq/kg. Three to 6 patients were treated at each
dose level. Total administered activities ranged from 602 to 3515 MBq,
and total antibody doses ranged from 1.6 to 6.4 mg. Complete blood
counts and biochemical profiles were performed at least once weekly. Toxicity was assessed according to the common criteria established by
the National Cancer Institute, version 2.0. We evaluated the biodistribution, pharmacokinetics, and dosimetry of
213Bi-HuM195 using methods described below and compared
differences between the first and last injections. To measure the
antileukemic effects of 213Bi-HuM195, we performed bone
marrow aspirations 7 to 10 days and 4 weeks following treatment.
