Diffusion-weighted MRI and Ga68-DOTATOC PET for early monitoring of response to intra-arterial Y90/Lu177-DOTATOC therapy in patients with neuroendocrine liver metastases

Objectives Monitoring response to therapy is predominantly based upon evaluating tumor size before and after treatment (i.e.RECIST criteria). However, alterations on a molecular basis may occur earlier than structural changes seen at imaging. Therefore we evaluated if diffusion-weighted MR imaging (DW-MRI) and Ga68-DOTATOC PET are potential surrogate biomarkers for providing earlier information about a possible treatment response to intraarterial DOTATOC therapy.

Methods In 12 consecutive patients with 29 liver metastases of gastroenteropancreatic neuroendocrine cancer (GEP-NET) were evaluated. All patients underwent both diffusion-weighted and Ga68-DOTATOC PET before and after last intra-arterial therapy. Largest diameter (LD), intratumoral apparent diffusion coefficient (ADC) and maximal standardized uptake value (SUVmax) were measured in all target lesions as well as in normal liver parenchyma and spleen.

Results Tumor metastases were subclassified, based upon change in tumor size in responding lesions (RL, n=7) and non-responding lesions (NRL, n=22). In NRLs, baseline median tumor ADC increased from 1,21 to 1,47x10 -3 mm 2/sec while the responding lesion increased from 1,06 to 1,32x10-3 mm2/sec after last loco-regional intervention (p<0,001, fig-1) whereas the change in SUVmax of (68)Ga-DOTATOC was not significantly different.

Conclusions After intra-arterial DOTATOC therapy non-responder and responder subgroups both presented a change in ADC, prior to SSR2-receptor expression changes and although morphological response according to RECIST criteria was only measurable in few lesions. Therefore, this work indicates that diffusion-weighted imaging seems to be an earlier tumor integrity surrogate for therapeutic intervention and possible early biomarker for treatment response