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J Nucl Med. 2008; 49 (Supplement 1):53P
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Oncology-Basic Science: Basic Science

Imaging - Antibodies and Constructs

Molecular imaging of bcl-2-positive and -negative SLL xenografts using peptide nucleic acid-peptide conjugates

F. Jia1, B. Balaji1, S. Figueroa3, F. Gallazzi2, T. Hoffman3 and M. Lewis1

1 Veterinary Medicine and Surgery; 2 Molecular Biology Program, University of Missouri-Columbia, Columbia, Missouri; 3 Research Service, Harry S Truman Memorial Veterans’ Hospital, Columbia, Missouri

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Objectives: The bcl-2 gene is overexpressed in non-Hodgkin’s lymphoma (NHL). Two peptide nucleic acid (PNA)-peptide conjugates targeting bcl-2 mRNA were investigated for direct comparison of bcl-2-positive and -negative cell lines and xenografts.

Methods: The human small lymphocytic lymphoma (SLL) cell lines Mec-1 and Ramos express comparable levels of somatostatin receptor subtype 2 for peptide nucleic acid-peptide delivery, but the Mec-1:Ramos bcl-2 mRNA expression ratio was determined by RT-PCR to be 3821:1. The cell lines were used in cell efflux studies, and the corresponding xenografts were used for in vivo distribution and imaging studies in SCID mice. DOTA-anti-bcl-2-PNA-Tyr-3-octreotate was labeled with In-111 (1). DOTA-anti-bcl-2-PNA-Ts-14-Tyr-3-octreotate was labeled with Cu-64 (2) for in vivo studies because micro-PET with this agent gave superior imaging quality.

Results: The cell associated radioactivity of conjugate 1 was 15% in Ramos cells, as compared with 60% in Mec-1 cells at 4 h of incubation. Biodistributions showed a 0.2% ID/g tumor uptake of conjugate 1 in Ramos mice and 1.3% ID/g in Mec-1 mice at 48 h post-injection. The conjugate 2 in Ramos mice showed a 0.7% ID/g tumor uptake and 1.1% ID/g in Mec-1 mice. Both conjugates could detect Mec-1 tumors by micro-SPECT and micro-PET, but not Ramos tumors.

Conclusions: The significantly (P<0.05) higher retention of conjugate 1 in Mec-1 cells suggested specific bcl-2 mRNA targeting. Biodistribution and imaging studies also concluded that both conjugates 1 and 2 specific for bcl-2 mRNA-positive tumor xenografts.

Research Support: CA103130





This Article
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Right arrow Alert me to new issues of the journal
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Right arrow Articles by Jia, F.
Right arrow Articles by Lewis, M.
PubMed
Right arrow Articles by Jia, F.
Right arrow Articles by Lewis, M.