Targeting Radiotherapy to Cancer by Gene Transfer

Abstract

<p>Targeted radionuclide therapy is an alternative method of radiation treatment which uses a tumor-seeking agent carrying a radioactive atom to deposits of tumor, wherever in the body they may be located. Recent experimental data signifies promise for the amalgamation of gene transfer with radionuclide targeting. This review encompasses aspects of the integration of gene manipulation and targeted radiotherapy, highlighting the possibilities of gene transfer to assist the targeting of cancer with low molecular weight radiopharmaceuticals.</p

Thrombocytopenia after meta-iodobenzylguanidine (MIBG) therapy in neuroblastoma patients may be caused by selective MIBG uptake via the serotonin transporter located on megakaryocytes

“…Although a large study performed by Trieu et al could not find significant association between both entities, this was attributed to the high-level and narrow range of MIBG activity applied (16.3 mCI/kg ± 5.9 [mean ± SD]). However, the whole-body radiation dose cannot explain the thrombocytopenia encountered in neuroblastoma patients treated with 125 I-MIBG, a radiopharmaceutical emitting Auger electrons with an insufficient range to interact with surrounding untargeted cells [ 41 ], which was more severe than in 131 I-MIBG-treated patients in the same study who received higher radiation doses [ 38 ]. Our finding that megakaryocytes are capable of selective MIBG uptake may explain these findings.…”

“…Interestingly, no association was found between bone marrow tumor infiltration at diagnosis and platelet reconstitution. We hypothesize that 131 I-MIBG taken up by megakaryocytes in the bone marrow might damage neighboring hematopoietic stem cells via cross-fire irradiation and radiation-induced biological bystander effects [ 41 , 43 ], leading to delayed platelet reconstitution after reinfusion. These two radiobiological effects may also partly account for the widespread and enduring hematological toxicity seen after 131 I-MIBG therapy.…”

Experimental Study of Nasopharyngeal Carcinoma Radionuclide Imaging and Therapy Using Transferred Human Sodium/Iodide Symporter Gene

“…Because of the limitations of current gene therapy technology, it is difficult to achieve 100% transfection rates with the target gene. Other studies [ 20 – 22 ] used gene therapy to produce a “bystander” effect, so that tumor cells, which did not carry the gene could also be killed. The range of β-particles emitted by 131 I is several millimetres, so surrounding untransfected tumor cells are likely to get damaged.…”

Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

“…The purpose of this treatment is to deliver a lethal dose of radiation to a tumour site while sparing as much healthy tissue as possible. Targeted radiotherapy seeks to deliver a lethal dose of radiation to tumours while minimizing damage to normal organs (Boyd et al 2004, Kufe and Weichselbaum 2003, Mitrofanova et al 2006, Mairs and Boyd 2003. Radiolabelled [ 131 I] meta-iodobenzylguanidine (MIBG), a low-LET β-par-ticle emitter, is used for the diagnosis and treatment of patients with tumours derived from the neural crest (Cunningham et al 2000, Mairs 1999).…”