Single tumor cell uptake and dosimetry of technetium-99m Fab' or minute anti-CD22 in low-grade B-cell lymphoma.
BACKGROUND
A patient with follicular lymphoma was investigated with 0.5 mg Fab' or minute anti-CD22 labeled with 1100 MBq technetium-99m ((99m)Tc). 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 (99m)Tc 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 the extrapolation of the absorbed dose from the patient's cells to a cell line with higher CD22 expression.


RESULTS
The average number of (99m)Tc 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 (99m)Tc targeted by Fab' or minute anti-CD22 in a patient's lymphoma using sorted cell populations, thereby allowing single cell dosimetry. Extrapolation of the absorbed dose from (99m)Tc 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 electron emitters to therapy.
Lindén
Ola
O
Department of Oncology, Lund University Hospital, Lund, Sweden. Ola.Linden@onk.lu.se
Hindorf
Cecilia
C
Tennvall
Jan
J
Segrén
Sverker
S
Wingardh
Karin
K
Strand
Sven-Erik
SE
D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D015815:Cell Adhesion Molecules; D016503:Drug Delivery Systems; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D037102:Lectins; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D011829:Radiation Dosage; D011874:Radiometry; D051918:Sialic Acid Binding Ig-like Lectin 2; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D013667:Technetium