Simon Puttick*, Bryan W. Day, Brett W. Stringer, Martina Jones, Christopher Howard, Stephen Mahler, Andrew Whittaker, Nicholas Dowson and Stephen Rose

 

The Australian Institute for Bioengineering and Nanotechnology
Corner of College and Cooper Roads
The University of Queensland
St Lucia, QLD 4072, Australia

 

The developing field of theranostics has made a significant impact on the management of cancer.1 Central to the theranostic paradigm is the ability to use diagnostic/therapeutic pairs of radionuclides (such as 68Ga and 177Lu) to predict the radiation dose received by a tumour and core organs from a PET image. Antibodies and their fragments are arguably one of the most promising candidates as theranostics due to their high biological stability, high specificity and high affinity to a target2 however are potentially limited by the low tumour:background ratio caused by long circulation times.

The calculation of total potential dose received by the tumour relative to non-tumour organs is critical in the evaluation of potential efficacy of theranostic platforms. In this talk I will outline the development of physiologically based pharmacokinetic (PBPK) models based on dynamic positron emission tomography data and their application in both dose prediction from multi-dosing regimens and extrapolation of pre-clinical data to the clinical setting.

Figure 1: Development of PBPK models to predict tumour and non-tumour dose from multi-dosing regimes of antibody based theranostics. Data from dynamic PET imaging is used to construct PBPK models which can be used to simulate multi-dose regimes
  1. Werner, R.A., Bluemel, C., Allen-Auerbach, M.S., Higuchi, T. & Herrmann, K. (68)Gallium- and (90)Yttrium-/(177)Lutetium: “theranostic twins” for diagnosis and treatment of NETs. Annals of Nuclear Medicine 29, 1-7 (2015).
  2. Larson, S.M., Carrasquillo, J.A., Cheung, N.-K.V. & Press, O.W. Radioimmunotherapy of human tumours. Nat Rev Cancer 15, 347-360 (2015).

Venue

Room: 
AEB Auditorium