Comparison of (99m)Tc-labeled PR81 and its F(ab')₂ fragments as radioimmunoscintigraphy agents for breast cancer imaging.

Abstract:

OBJECTIVE:We digested anti-MUC1 monoclonal antibody PR81 to produce F(ab')₂ fragments. A comparison was performed between the two radiolabeled PR81 and F(ab')₂ fragments for breast tumor imaging in a mouse model. METHODS:The optimum conditions for pepsin digestion of PR81 were investigated in terms of enzymes: antibody ratio, digestion time duration and preserved immunoreactivity of the produced fragments. The F(ab')₂ fragments were labeled with Technetium-99m using HYNIC as a chelator and tricine as a co-ligand. The immunoreactivity of the complexes was assessed by radioimmunoassay using MCF7 cells. Biodistribution and imaging studies were performed in female BALB/c mice with breast tumor xenograft at 4, 8 and 24 h post-administration. The PR81 was labeled with technetium-99m in the same way for comparison. RESULTS:The optimum time duration for PR81 digestion was found to be 28 h at an enzyme:antibody weight ratio of 1:20 that resulted in 95.2 ± 4.7% purity. The labeling of intact PR81 and its F(ab')₂ fragments were 87.6 ± 4.2 and 76.1 ± 3.3% after 1 h, respectively (p value <0.05). The percentage of immunoreactivity of F(ab')₂ fragments and intact PR81 were 75.4 ± 2.1% and 85.7 ± 2.9%, respectively (p value <0.05). The biodistribution and imaging studies demonstrated localization of the fragments at 4 h post-administration with high sensitivity and specificity. CONCLUSION:The results showed that F(ab')₂ fragment of PR81 is more suitable than intact PR81 for safer and more rapid detection of human breast cancer.

journal_name

Ann Nucl Med

authors

Salouti M,Babaei MH,Rajabi H,Foroutan H,Rasaee MJ,Rajabi AB,Mohammadnejad J,Shafiee M,Mazidi M,Daha FJ

doi

10.1007/s12149-010-0434-2

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

87-92

issue

2

eissn

0914-7187

issn

1864-6433

journal_volume

25

pub_type

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