Successful imaging of malignant melanoma with technetium-99m-labeled monoclonal antibodies.
F(ab')2 and Fab fragments of murine monoclonal antibody 9.2.27, that recognizes the 250 kD melanoma-associated antigen, were labeled with 99mTc using the bifunctional chelate method of Fritzberg et al. Twenty-seven (27) patients received, intravenously, 10 mg of either F(ab')2 (8), or the Fab (27), labeled with up to 30 mCi of 99mTc. These doses were preceded by an infusion of cold irrelevant antibody. The average serum T1/2 of the F(ab')2 and the Fab were 11 hr and 2 hr, respectively. Twenty-two percent (22%) of the total injected F(ab')2 dose was excreted in the urine in 20 hr, compared to 55% for the Fab group. Imaging was optimal 6-9 hr postinjection for the Fab patients. No nonspecific uptake in liver, spleen, bone marrow, or lung was observed for either antibody form. Overall, (43/53) 81% of known metastases were seen with visualization of tumors as small as 250 mg and tumor localization as high as 0.03% injected dose/g. Immunoperoxidase staining of freshly-frozen tumor nodules removed 24 hr postinjection confirmed antibody deposition in the tumor. Thirty-six previously unknown ("occult") metastatic sites were detected. To date, 12/36 of these sites have been confirmed. We conclude that 99mTc-labeled antibody to melanoma produces high resolution images with a high sensitivity of detecting metastatic melanoma. The detection of previously unknown sites of disease has proven helpful in directing additional diagnostic studies (i.e., CT) as well as planning of therapeutic options.
Eary
J F
JF
Division of Nuclear Medicine, University of Washington, Seattle.
Schroff
R W
RW
Abrams
P G
PG
Fritzberg
A R
AR
Morgan
A C
AC
Kasina
S
S
Reno
J M
JM
Srinivasan
A
A
Woodhouse
C S
CS
Wilbur
D S
DS
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000556:secondary; D011877:Radionuclide Imaging; D013667:Technetium
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007140:Immunoglobulin Fab Fragments; D013667:Technetium