Late apoptotic effects after treatment with ¹⁷⁷Lu-octreotate in small-intestine neuroendocrine GOT1 tumor model

Therapy with hyperfractionated administration of ¹⁷⁷Lu-octreotate gave larger reductions of GOT1 tumor volume than single administration of the same amount of radiopharmaceutical. The molecular mechanisms behind this response need to be examined. The aims of this work were to compare the expression of genes involved in apoptosis in GOT1 tumors during growth phase from mice treated with ¹⁷⁷Lu-octreotate and from untreated mice, and to compare gene expression in regrown GOT1 tumors after single and hyperfractionated administration. The study was performed on tumor samples previously collected and analyzed by other methods. BALB/c mice, bearing GOT1 tumors, were treated i.v. with 2x15 MBq or 1x30; 2x30 or 1x60 MBq; 3x40, 2x60, or 1x120 MBq ¹⁷⁷Lu-octreotate. Controls were given saline. After tumor volume reduction and regrowth, the mice were euthanized and tumors collected, RNA was extracted and analyzed by PCR Array for expression of 84 apoptosis-related genes. Expression of each gene was compared with that in controls. Pathway analysis was performed. The highest regulated gene, compared to untreated controls, was <i>RIPK2</i> in the group that received 3x40 MBq of ¹⁷⁷Lu-octreotate. The most frequently regulated gene among the groups in the study was the pro-apoptotic <i>TNFSF8</i>. Most genes in the study were upregulated. The │FC│-values were all below 3.5. The study present similarities and differences in molecular response between the groups of different ¹⁷⁷Lu-octreotate treatments. The results may have impact on the optimization of therapy in the future.