04:21 PM Abstract No. 430 Novel method of implantation and retrieval of a miniature microdevice for in vivo cancer drug evaluation

Abstract

A recently developed microdevice allows cancer drugs to be tested in vivo prior to systemic treatment. When placed in a tumor, it delivers drug microdoses into adjacent tissue over 24hrs. When removed, analysis of exposed tissue may predict treatment response, obviating expensive and potentially morbid clinical trials. Tissue analysis currently requires surgical removal. We demonstrate feasibility of percutaneous microdevice implantation, securement, and tissue retrieval for in vivo drug testing. We prototyped a 6mm long, 625-μm-diameter retrievable microdevice that delivers drugs at 10 discrete sites of surrounding tissue. Ten microdevices were implanted in ex-vivo phantoms using a customized 16-gauge needle and retrieved under US guidance using a custom prototyped retrieval needle. After IACUC approval, microdevices preloaded with Doxorubicin were implanted into 3 mouse colon cancer and 2 melanoma tumors in vivo, left for 24 hrs during drug release, and microdevice retrieval/tissue biopsy was performed under US guidance. Successful retrieval and biopsy was defined as retrieval of the microdevice and intact adjacent tissue sample containing at least 4/10 drug delivery sites with sample thickness >100μm at each site. Fluorescent imaging of Doxorubicin confirmed drug delivery within the tissue; apoptosis staining was performed to assess in vivo tissue response. Successful microdevice implantation and retrieval was achieved in 9/10 ex vivo phantom attempts and in the 5 in vivo tumors. An average of 6.8/10 discrete tissue sites containing micro-doses of delivered drug were retrieved per attempt, indicating feasibility of multi-drug testing. The tissue regions of drug delivery, as assessed with fluorescent Doxorubicin drug signal, correlated with apoptosis staining in all in vivo models, indicating in vivo drug efficacy. No animal distress was noted during microdevice implantation, 24-hour observation, or retrieval. Percutaneous implantation and retrieval of a novel microdevice that may be able to predict chemotherapy response to multiple drugs in vivo is feasible and has the potential to improve personalized approaches to oncology. Clinical trials are planned.