In vitro evaluation of targeted antisense 177Lu radiotherapy.

Abstract:

BACKGROUND:The BCL2 proto-oncogene in non-Hodgkin's lymphoma is a dominant inhibitor of apoptosis. The goal of this work was to develop a (177)Lu-labeled anti-BCL2-peptide nucleic acid (PNA) conjugate designed for dual modality NHL therapy, i.e., simultaneous down-regulation of BCL2-mediated resistance to apoptosis and delivery of cytotoxic internally emitted radiation. MATERIALS AND METHODS:The effect of 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetra-acetic acid (DOTA)-anti-BCL2-Tyr(3)-octreotate was evaluated by uptake, efflux, proliferation, and viability assays, using Mec-1 lymphoma cells. In vitro dosimetry was modeled with a Monte Carlo projection. RESULTS:Cellular efflux indicated moderate retention of radioactivity in the Mec-1 cells. Viability studies using the (177)Lu-labeled PNA conjugate indicated a mass-dose dependence and strongly additive statistical effect in reducing cellular viability. CONCLUSION:These studies demonstrate the ability of a BCL2 antisense PNA conjugate to specifically target, be retained in, and reduce cellular viability in Mec-1 NHL cells. The results also hold promise for the development of a therapeutic radiopharmaceutical with potential dual modality function.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Balkin ER,Jia F,Miller WH,Lewis MR

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

3143-9

issue

10

eissn

0250-7005

issn

1791-7530

pii

31/10/3143

journal_volume

31

pub_type

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