Maximizing radiotracer delivery to experimental atherosclerotic lesions with high-dose, negative charge-modified Z2D3 antibody for immunoscintigraphic targeting

Jagat Narula, Artiom Petrov, Charles Ditlow, Koon Yan Pak, Francis W. Chen, Ban An Khaw

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background. Two factors that directly affect target/background ratio in immunoscintigraphy are the concentration of the antibody bound to the target and the concentration of the antibody in the circulation. High dosages of monoclonal antibody have been reported to be more efficacious in visualization of tumors. Although administration of a higher dosage of antibody increases the absolute target accumulation of the radiotracer, it also increases the background activity, which may offset this advantage. Negative charge-modified antibodies carry high specific radioactivity to the target sites without significantly increasing the background activity. Therefore we investigated whether higher dosages of negative charge-modified antibody can be used to improve imaging of experimental atherosclerotic lesions. Methods and Results. Experimental atherosclerotic lesions were produced in 16 New Zealand White rabbits by balloon deendothelialization of the infradiaphragmatic aorta and hyperlipidemic diet for 12 weeks. Negative charge-modified Z2D3 antibody F(ab')2 specific for an antigen on proliferating smooth muscle cells of human atheroma labeled with 111In was used for imaging experimental atherosclerotic lesions either at high (100 to 125 μg) or low (25 to 50 μg) dosages. A lower dosage of Z2D3 was labeled with 507 ± 29.5 μCi (25 to 50 μg) 111In label, compared with 2.9 ± 0.24 mCi (100 to 125 μg) for the higher dosage. Although noninvasive visualization of atherosclerotic lesions was possible in all animals at 24 hours, high antibody dose allowed unequivocal visualization of the lesion as early as 3 hours after intravenous administration of the antibody. Eight animals were killed at 24 hours and the remaining eight animals at 48 hours. Mean radioactivity dose delivered per gram of lesion with the low-dose protocol at 24 hours was 0.46 ± 0.09 μCi, which remained essentially unchanged at 48 hours (0.37 ± 0.09 μCi; p = 0.51). With the high-dosage protocol, the total radioactivity (dose) per gram uptake in the lesion increased by about eightfold (3.49 ± 0.58 μCi; p = 0.002) at 24 hours and was sixfold higher at 48 hours (2.21 ± 0.45 μCi; p < 0.02). Conclusions. The study demonstrated that the increase in the dosage of negatively charge-modified antibody allows a very high delivery of specific radioactivity to the target, which in turn enables early visualization of experimental atherosclerotic lesions.

Original languageEnglish
Pages (from-to)226-233
Number of pages8
JournalJournal of Nuclear Cardiology
Volume4
Issue number3
DOIs
StatePublished - 1997

Keywords

  • Angioplasty
  • Antibody
  • Atherosclerosis
  • Gamma imaging
  • Hyperlipidemia
  • Smooth muscle cells

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