Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics

Molecular radiotherapy, or targeted radionuclide therapy, uses systemically administered drugs bearing a suitable radioactive isotope, typically a beta emitter. These are delivered via metabolic or other physiological pathways to cancer cells in greater concentrations than to normal tissues. The absorbed radiation dose in tumour deposits causes chromosomal damage and cell death. A partner radiopharmaceutical, most commonly the same vector labelled with a different radioactive atom, with emissions suitable for gamma camera or positron emission tomography imaging, is used to select patients for treatment and to assess response. The use of these pairs of radio-labelled drugs, one optimised for therapy, the other for diagnostic purposes, is referred to as theragnostics. Theragnostics is increasingly moving away from a fixed number of defined activity administrations, to a much more individualised or personalised approach, with the aim of improving treatment outcomes, and minimising toxicity. There is, however, still significant scope for further progress in that direction. The main tools for personalisation are the following: imaging biomarkers for better patient selection; predictive and post-therapy dosimetry to maximise the radiation dose to the tumour while keeping organs at risk within tolerance limits; imaging for assessment of treatment response; individualised decision making and communication about radiation protection, adjustments for toxicity, inpatient and outpatient care.

Probability, interpretations of

The term ‘probability’ and its cognates occur frequently in both everyday and philosophical discourse. Unlike many other concepts, it is unprofitable to view ‘probability’ as having a unique meaning. Instead, there exist a number of distinct, albeit related, concepts, of which we here mention five: the classical or equiprobable view, the relative frequency view, the subjectivist or personalist view, the propensity view, and the logical probability view. None of these captures all of our legitimate uses of the term ‘probability’, which range from the clearly subjective, as in our assessment of the likelihood of one football team beating another, through the inferential, as when one set of sentences lends a degree of inductive support to another sentence, to the obviously objective, as in the physical chance of a radioactive atom decaying in the next minute. It is often said that what all these interpretations have in common is that they are all described by the same simple mathematical theory – ‘the theory of probability’ to be found in most elementary probability textbooks – and it has traditionally been the task of any interpretation to conform to that theory. But this saying does not hold up under closer examination, and it is better to consider each approach as dealing with a separate subject matter, the structure of which determines the structure of the appropriate calculus.

Bell's conspiracy, Schrödinger's black cat and global invariant sets

A locally causal hidden-variable theory of quantum physics need not be constrained by the Bell inequalities if this theory also partially violates the measurement independence condition. However, such violation can appear unphysical, implying implausible conspiratorial correlations between the hidden variables of particles being measured and earlier determinants of instrumental settings. A novel physically plausible explanation for such correlations is proposed, based on the hypothesis that states of physical reality lie precisely on a non-computational measure-zero dynamically invariant set in the state space of the universe: the Cosmological Invariant Set Postulate. To illustrate the relevance of the concept of a global invariant set, a simple analogy is considered where a massive object is propelled into a black hole depending on the decay of a radioactive atom. It is claimed that a locally causal hidden-variable theory constrained by the Cosmological Invariant Set Postulate can violate the Clauser–Horne–Shimony–Holt inequality without being conspiratorial, superdeterministic, fine-tuned or retrocausal, and the theory readily accommodates the classical compatibilist notion of (experimenter) free will.

Targeting Radiotherapy to Cancer by Gene Transfer

Targeted radionuclide therapy is an alternative method of radiation treatment which uses a tumor-seeking agent carrying a radioactive atom to deposits of tumor, wherever in the body they may be located. Recent experimental data signifies promise for the amalgamation of gene transfer with radionuclide targeting. This review encompasses aspects of the integration of gene manipulation and targeted radiotherapy, highlighting the possibilities of gene transfer to assist the targeting of cancer with low molecular weight radiopharmaceuticals.