Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer.

1990 ◽  
Vol 8 (12) ◽  
pp. 1941-1950 ◽  
Author(s):  
J S Stewart ◽  
V Hird ◽  
D Snook ◽  
B Dhokia ◽  
G Sivolapenko ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Radiation Dose ◽  
Tumor Regression ◽  
Radiation Doses ◽  
Internal Radiation ◽  
Bone Absorption ◽  
Medical Internal Radiation Dose ◽  
Yttrium 90

From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient.

Targeted Radiotherapy in the Conditioning Prior to Haematopoietic Stem Cell Transplantation: Results of a Phase I Radiation Dose Escalation Study Using Yttrium-90-Labelled Anti-CD66 Monoclonal Antibody Demonstrating High BM Uptake of Radiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2189-2189
Author(s):  
Kim Orchard ◽  
Margaret Cooper ◽  
Valerie Lewington ◽  
Maria Tristram ◽  
Maureen Zivanovic ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Stem Cell ◽  
Radiation Dose ◽  
Dose Escalation ◽  
Radiation Doses ◽  
Dose Escalation Study ◽  
Dose Levels ◽  
Reduced Intensity ◽  
Yttrium 90

Abstract We report the results of a phase I clinical study using a radiolabelled murine anti-CD66 IgG1 monoclonal antibody (TheraPharm GmbH) as part of the transplant conditioning schedule for patients receiving either autologous or allogeneic stem cell transplants (SCT) for myeloma or acute myeloid leukaemia. This was a radiation dose escalation study using increasing doses of yttrium-90 (Y-90) as the therapeutic radionuclide. A total of eighteen patients have been treated over four Y-90 radiation dose levels. All patients received an initial infusion of indium-111 (In-111)-labelled anti-CD66 for biodistribution and dosimetry determination. If favourable dosimetry was demonstrated, patients went on to receive the therapy dose of radiation, the dose of Y-90 infused calculated from the patient’s body weight. The Y-90 dose levels were as follows: 5, 10, 25 and 37.5MBq /kilogram (lean) body weight. Patient characteristics: Age 21-67 yrs (median 54 yrs); 14 male, 4 female; myeloma 14, AML 4; autologous SCT 14, reduced intensity allogeneic SCT 4. Patients undergoing autologous SCT for myeloma received Y-90 labelled anti-CD66 on day -14 and melphalan 200mg/m2 on day -2. Patients undergoing reduced intensity allogeneic SCT received Y-90-labelled anti-CD66 on day -14 in addition to a reduced intensity schedule of fludarabine, melphalan and CAMPATH 1H. Results: Excellent bone marrow targeting was seen in all patients and in the majority low uptake by non-haematopoietic organs, in particular liver uptake was consistently low. There was a close correlation between the administered dose of Y-90 and the dose delivered to the bone marrow but not for the radiation dose received by the liver. Mean absorbed radiation doses (cGy per MBq infused Y-90): bone marrow 10.23 +/- 1.8 cGy/MBq; liver 2.67 +/- 2.0 cGy/MBq; spleen 7.10 +/- 3.75 cGy/MBq. Total absorbed radiation doses at each dose level are in table 1. Table 1 Organ dose in Gy Dose level MBq per kg BM Liver Spleen 5 4.1 1.4 1.1 10 9.1 1.3 2.4 25 15.6 3.7 12.6 37.5 22.0 7.8 5.3 No additional toxicity due to the addition of targeted radiation was seen. Engraftment: neutrophils >0.5 by day + 13.8 (11-22) platelets >50 day +12.7 (10-22), no graft failures were seen. In two patients with myeloma, focal uptake of In-111-labelled antibody was seen suggesting in vivo targeting of myeloma, consistent with the expression of the antigen on plasma cells demonstrated by Flow cytometry. Conclusions: The anti-CD66 monoclonal antibody showed consistently excellent BM targeting and very low uptake by non-haematopoietic organs. Up to 25 Gy of additional radiation was delivered to the bone marrow with no additional toxicity. This particular monoclonal antibody may have a role in stem cell transplantation for a wide range of haematological malignancies, providing significant dose escalation without toxicity in autologous and allogeneic protocols. AntiCD66 may be particularly appropriate in transplantation for myeloma.

Dosimetrie bei Anwendung von 131I bei benignen Schilddrüsenerkrankungen: DIN 6861-1

Radiopraxis ◽  
2018 ◽  
Vol 11 (04) ◽  
pp. E30-E40
Author(s):  
Heribert Hänscheid ◽  
Frederik A. Verburg
Keyword(s):  
Nuclear Medicine ◽  
Radiation Dose ◽  
European Association ◽  
Internal Radiation ◽  
Medical Internal Radiation Dose

Bei der Behandlung benigner Schilddrüsenerkrankungen mit 131I ist eine prätherapeutische Dosimetrie zur Bemessung der Therapieaktivität und eine Abschätzung der therapeutisch verabreichten Energiedosis in Deutschland gesetzlich vorgeschrieben. Zur Durchführung der Dosimetrie existieren Handlungsempfehlungen der Deutschen Gesellschaft für Nuklearmedizin und der European Association of Nuclear Medicine. Um Methodik und Verfahrensablauf der Dosisbestimmungen national weiter zu harmonisieren, wird aktuell die Norm DIN 6861 – 1 erstellt. Die DIN 6861 – 1 übernimmt viele Empfehlungen der Leitlinien als Forderungen und führt bei den Berechnungen zu vergleichbaren Ergebnissen. Im Detail finden sich aber auch Unterschiede, z. B. wird bei den Berechnungen die Abhängigkeit der absorbierten Energiedosis von der Größe des therapierten Volumens explizit berücksichtigt. Beim Formalismus verlässt die DIN 6861 – 1 die tradierten Schreibweisen und verwendet die international zunehmend als Standard für die Dosimetrie bei innerer Exposition akzeptierte Nomenklatur des Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Dem Nutzer wird durch die neue DIN-Norm zudem eine vollständige Liste der für eine nachvollziehbare Dosimetrie notwendigen Dokumentation an die Hand gegeben.

Leukemia risk following radiotherapy for breast cancer.

1989 ◽  
Vol 7 (1) ◽  
pp. 21-29 ◽  
Author(s):  
R E Curtis ◽  
J D Boice ◽  
M Stovall ◽  
J T Flannery ◽  
W C Moloney
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Radiation Dose ◽  
Cell Transformation ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Radiation Doses ◽  
Entire Body ◽  
Medical Physicists

To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.

scholarly journals Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1329-1337 ◽  
Author(s):  
Yu-Tzu Tai ◽  
Myles Dillon ◽  
Weihua Song ◽  
Merav Leiba ◽  
Xian-Feng Li ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Cell Adhesion ◽  
Tumor Regression ◽  
Myeloma Cell ◽  
Hsp90 Inhibitor ◽  
Cellular Cytotoxicity ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Healthy Donors ◽  
Human Multiple Myeloma

Abstract Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.

scholarly journals ASSESSMENT OF QUALITATIVE CHANGES IN PERIPHERAL BLOOD CELLS IN CHILDREN – RESIDENTS OF RADIOLOGICALLY CONTAMINATED TERRITORIES IN THE LATE PERIOD AFTER THE ChNPP ACCIDENT

2021 ◽  
Vol 26 ◽  
pp. 297-308
Author(s):  
V. Bebeshko ◽  
◽  
K. Bruslova ◽  
L. Lyashenko ◽  
T. Pushkariova ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Comparison Group ◽  
Blood Parameters ◽  
Radiation Doses ◽  
Peripheral Blood Cells ◽  
Internal Radiation ◽  
Somatic Diseases ◽  
Qualitative Changes

Objective: to establish the relationship between quantitative and qualitative parameters of peripheral blood cells (lymphocytes, neutrophilic granulocytes, monocytes, platelets) depending on the type of somatic diseases and annual internal radiation doses from 137Cs in children – residents of radiologically contaminated territories in the late period after the Chornobyl Nuclear Power Plant (ChNPP) accident. Materials and methods. There were 175 children included in the study comprising residents of radiologically contaminated territories (n = 79) aged from 4 to 18 years. Annual internal radiation doses in children from 137Cs ranged from 0.004 to 0.067 mSv. Certain blood parameters were assessed in a comparative mode in children having got the radiation doses up to 0.01 mSv and higher. The comparison group (n = 96) included children living in settlements not attributed to the radiologically contaminated ones. Incidence and type of somatic diseases and its impact on quantitative and qualitative changes in blood parameters (i.e. lymphocyte, neutrophilic granulocyte, monocyte, and platelet count) were studied. The cell size, state of nucleus, membranes and cytoplasm, signs of proliferative and degenerative processes were taken into account. Results. Incidence and type of somatic diseases in children did not depend on the annual internal radiation dose. Number of cases of monocytosis was significantly higher among the children exposed to ionizing radiation than in the comparison group (16.6 % vs. 7.3 %). There were, however, no correlation between these changes and radiation doses. Number of activated blood monocytes with cytoplasmic basophilia and residues of nucleoli in nuclei was higher in individuals with internal radiation doses > 0.01 mSv. A direct correlation between the qualitative parameters of monocytes and internal radiation doses was established (rs = 0.60; р < 0.001), as well as a direct correlation of different strength between qualitative parameters of blood cells, indicating their unidirectional pattern depending on the somatic morbid conditions. Regardless of annual internal radiation dose, there was an increase in the number of degenerative and aberrant cells vs. the comparison group (р < 0.05), which could be due to the role of non-radiation factors. Conclusions. Results of the assessment of quantitative and qualitative parameters of peripheral blood cells reflected the state of morbid conditions in children and are of a diagnostic value. The identified dose-dependent changes in monocyte lineage of hematopoiesis may be the markers of impact of long-term radionuclide incorporation with food in children living in environmentally unfavorable conditions after the ChNPP accident. Key words: annual internal radiation dose from 137Cs, children, peripheral blood, lymphocytes, neutrophilic granulocytes, monocytes, platelets, qualitative signs.

Dosimetrie bei Anwendung von 131I bei benignen Schilddrüsenerkrankungen: DIN 6861-1

2018 ◽  
Vol 41 (01) ◽  
pp. 13-23
Author(s):  
Heribert Hänscheid ◽  
Frederik Verburg
Keyword(s):  
Nuclear Medicine ◽  
Radiation Dose ◽  
European Association ◽  
Internal Radiation ◽  
Medical Internal Radiation Dose

ZusammenfassungBei der Behandlung benigner Schilddrüsenerkrankungen mit 131I ist eine prätherapeutische Dosimetrie zur Bemessung der Therapieaktivität und eine Abschätzung der therapeutisch verabreichten Energiedosis in Deutschland gesetzlich vorgeschrieben. Zur Durchführung der Dosimetrie existieren Handlungsempfehlungen der Deutschen Gesellschaft für Nuklearmedizin und der European Association of Nuclear Medicine. Um Methodik und Verfahrensablauf der Dosisbestimmungen national weiter zu harmonisieren, wird aktuell die Norm DIN 6861 – 1 erstellt. Die DIN 6861 – 1 übernimmt viele Empfehlungen der Leitlinien als Forderungen und führt bei den Berechnungen zu vergleichbaren Ergebnissen. Im Detail finden sich aber auch Unterschiede, z. B. wird bei den Berechnungen die Abhängigkeit der absorbierten Energiedosis von der Größe des therapierten Volumens explizit berücksichtigt. Beim Formalismus verlässt die DIN 6861 – 1 die tradierten Schreibweisen und verwendet die international zunehmend als Standard für die Dosimetrie bei innerer Exposition akzeptierte Nomenklatur des Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Dem Nutzer wird durch die neue DIN-Norm zudem eine vollständige Liste der für eine nachvollziehbare Dosimetrie notwendigen Dokumentation an die Hand gegeben.

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