PT  - JOURNAL ARTICLE
AU  - Falzone, Nadia
AU  - Myhra, Sverre
AU  - Nathan, Roger
AU  - Chakalova, Radka
AU  - Altebaeumer, Thomas
AU  - Cornelissen, Bart
AU  - Vallis, Katherine
TI  - Chemically amplified photoresist as a medium for quantitative 3-D high spatial resolution autoradiography
DP  - 2011 May 01
TA  - Journal of Nuclear Medicine
PG  - 132--132
VI  - 52
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/52/supplement_1/132.short
4100  - http://jnm.snmjournals.org/content/52/supplement_1/132.full
SO  - J Nucl Med2011 May 01; 52
AB  - 132 Objectives Dosimetry of radiopharmaceuticals used for targeted radiotherapy (tRT) is dependent on the overall and intracellular distribution of the radioisotope. Knowledge about the intracellular distribution is often limited as it is based on cellular fractionation studies. We investigated the use of photoresist materials, sensitive to the Auger and internal conversion (IC) electron emissions of indium (111In) currently used for tRT, as a direct and quantitative method for subcellular nano-autoradiography. Methods MDA-MB-468 breast cancer cells that overexpress epidermal growth factor (EGF) receptors were exposed to 111In-labelled-EGF. Exposed cells and isolated nuclei were deposited on chemically amplified positive photoresists (UV1116 and AZ40XT). After a period of 4 half-lives, the resist material was chemically developed and evaluated by atomic force microscopy (AFM). Electron beam lithography of known electron flux was used to calibrate the resist response, while Monte Carlo (MC) simulation was used to quantify electron dose distribution originating from the radio-labelled cells. Results AFM analysis showed a non-uniform distribution of 111In-EGF in the cell and nucleus, comparable to confocal microscopy and micro-autoradiography. Photoresist exposure to IC and Auger electrons, resulted in up to 50 nm deep surface depressions, which correspond to an electron flux ranging from 1 - 40 μC/cm2, equivalent to 0.08 - 0.19 mGy deposited dose. Conclusions This novel technique provides a nm scale mapping of the energy deposition pattern and intra-cellular and nuclear bio-distribution of 111InIn. Furthermore, the method can be adapted to evaluate intra-cellular bio-distribution of other radioisotopes. Research Support Medical Research Council (MRC) Cancer Research UK (CRUK