The B-cell lymphoma/leukemia-2 (bcl-2) proto-oncogene is a dominant inhibitor of apoptosis in B-cell non-Hodgkin's lymphoma (NHL).  Our goal was to develop a radiolabeled bcl-2 antisense peptide nucleic acid (PNA)-Tyr3-octreotate conjugate designed for dual modality NHL therapy, consisting of a radiopharmaceutical capable of simultaneously down-regulating apoptotic resistance and delivering cytotoxic internally emitted radiation.  This conjugate was radiolabeled with 177Lu by conjugating the PNA-peptide to 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA).  The biodistribution of the 177Lu-labeled bcl-2 antisense PNA-peptide showed specific tumor targeting in mice bearing Mec-1 human NHL xenografts.  In vivo tumor saturation studies determined that 50 �g of the compound provided the maximum antisense effect.  Compared to controls, preliminary radiotherapy studies showed a significantly longer tumor growth delay in mice treated with the 177Lu-labeled antisense PNA-peptide.  This effect was most noticeable when 50 �g of the unlabeled compound was administered 1 h after injection of 120 �Ci of the radiolabeled PNA-peptide.

Targeted antisense radiotherapy using a <sup>177</sup>Lu-labeled peptide nucleic acid in B-cell non-Hodgkin's lymphoma

243rd National Meeting (2012)

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Targeted antisense radiotherapy using a 177Lu-labeled peptide nucleic acid in B-cell non-Hodgkin's lymphoma

Targeted antisense radiotherapy using a ¹⁷⁷Lu-labeled peptide nucleic acid in B-cell non-Hodgkin's lymphoma