1.
Hindorf, Cecilia, et al.
(author)
Time dependence of the activity concentration ratio of red marrow to blood and implications for red marrow dosimetry.
2002
In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:4 Suppl, s. 1235-1239
Journal article (peer-reviewed) abstract
BACKGROUND: The method for red marrow dosimetry in radioimmunotherapy, in the absence of specific activity uptake in red marrow, is based on the activity measured in the blood or plasma. The activity concentration ratio of red marrow to blood is then assumed to be constant. The aim of the current study was to determine whether this ratio varies with time after injection. METHODS: Measurements were carried out with both animals and patients.Tumor-bearing rats were intravenously injected with iodine-131-, iodine-125-, indium-111-, or rhenium-188-labeled BR96, a chimeric immunoglobulin G1 monoclonal antibody. (All were chelate-labeled, except for iodine-131, which was iodogen-labeled.) Measurements were made of the activity concentration in blood and bone marrow at different points in time after injection, and the ratio of activity concentration in red marrow and blood as a function of time postinjection (RMBLR[t)]) was calculated. For patients treated with iodine-131-labeled monoclonal antibody (LL2, Immunomedics Inc., Morris Plains, NJ; anti-CD22; immunoglobulin G2 isotype of mouse origin), blood samples were drawn and scintillation camera images taken at different times after injection. The red marrow activity concentration in the sacrum was determined by activity quantification from regions of interest. The activity concentration in blood was also measured. The RMBLR(t) was calculated based on these data. RESULTS: For both patients and rats, the RMBLR(t) was increased 72 hours after injection. Furthermore, it was found that the use of a constant RMBLR can lead to an over- or underestimation of the absorbed dose in bone marrow. CONCLUSIONS: These data demonstrate the difficulty in using fixed values of the activity concentration ratio of red marrow to blood for dosimetry.
2.
Lindén, Ola, et al.
(author)
131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas failing chemotherapy. Treatment outcome, haematological toxicity and bone marrow absorbed dose estimates.
2002
In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 297-303
Journal article (peer-reviewed) abstract
The experience with radioimmunotherapy in B-cell lymphomas using the rapidly internalizing antibody, anti-CD22 (LL2), is limited. In this study we investigated the efficacy and toxicity of 131I-labelled-LL2 for radioimmunotherapy in patients with B-cell lymphomas that failed one or two cytostatic regimens. Eleven patients were treated with one or repeated cycles of 131I-anti-CD22 antibody, 1330 MBq/m2 (36 mCi/m2). Six of the 11 treated patients demonstrated an objective response, three of them with complete remission. All follicular (3 patients) and transformed lymphomas (2 patients) responded compared to one of four diffuse large B-cell lymphomas. Two out of six responders exhibited event-free survival (EFS), which was comparable with or longer than the EFS following primary anthracycline-containing chemotherapy. Non-haematological toxicity was mild. Haematological toxicity was associated with pretreatment clinical characteristics but not with estimated absorbed bone marrow doses. Objective remission following treatment with 131I-anti-CD22 can be achieved in patients with various subtypes of B-cell lymphomas, failing standard chemotherapy. Follicular or transformed lymphomas seem particularly responsive. Haematological toxicity seems to be dependent on the functional status of the bone marrow before radioimmunotherapy.
3.
Lindén, Ola, et al.
(author)
Single tumor cell uptake and dosimetry of technetium-99m Fab ' anti-CD22 in low-grade B-cell lymphoma
2002
In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 94:4, s. 1270-1274
Journal article (peer-reviewed) abstract
BACKGROUND. A patient with follicular lymphoma was investigated with 0.5 mg Fab' anti-CD22 labeled with 1100 MBq technetium-99m (Tc-99m). A computed tomography scan performed a week later revealed regression. This unexpected response prompted an investigation of single cell dosimetry of low-energy electron emitters. METHODS. Another patient with low-grade, unclassifiable B-cell lymphoma with a low expression of CD22 was injected with Tc-99m anti-CD22. Blood samples were drawn 30 minutes, 4 hours, and 24 hours after injection. Lymphoma cells (CD19+) and T cells (CD3+), which served as control cells, were separated using a flow cytometer. The radioactivity of the two cell Populations was Measured in an NaI(Tl) well-type detector. The mean uptake per cell and absorbed dose were calculated. The CD22 expression of the patient's cells and of a B-cell lymphoma cell line (Raji) were assessed by flow cytometry for die extrapolation of the absorbed dose from the patient's cells to a cell line with higher CD22 expression. RESULTS. The average number of Tc-99m atoms per CD19+ and CD3 cell 4 hours postinjection were 5.4 and 0.054, respectively. Depending on the assumed ratio between antibody and CD22 molecules (1:2 or 1:1), the CD22 expression on the patient's cells and Raji cells varied from 2800 to 5700 and from 37,000 to 74,000 per cell, respectively. The average absorbed dose per cell ranged from 4 x 10(-7) to 0.1 grays (Gy). CONCLUSIONS. It seems feasible to assess the mean single tumor cell uptake of Tc-99m targeted by Fab' anti-CD22 in a patient's lymphoma using sorted cell populations, thereby allowing single cell dosimetry. Extrapolation of the absorbed dose from Tc-99m to cells with higher CD22 expression was made and under certain conditions absorbed doses of 0.1 Gy were obtained, indicating the potential relevance of low-energy elCancer 2002;94:1270-4.
