Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics

Abstract

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.

A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N

“…Neuroblastoma is known to be a radiosensitive disease, although if the disease is localized in several different sites external beam radiotherapy is not suitable. Therefore, targeted molecular radiotherapy is a more attractive treatment option in this setting, as it delivers tumor specific radiation and can target multiple sites of disease from the same administration (8)(9)(10)(11)(12)(13)(14). Studies have shown that 85-90% of neuroblastomas express the noradrenaline transporter molecule and can be targeted with the catecholamine analog, meta-iodobenzylguanidine (mIBG), labeled with 123 I for imaging and with the β-emitter 131 I for therapy.…”

Calix[4]crowns with perfluoroalkylsulfonylcarboxamide functions: a complexation approach for heavy group 2 metal ions

“…25,26 In addition, the combination of the gamma emitter 131 Ba for diagnosis and both alpha emitters 223/224 Ra for therapy is beneficial and leads to a matched nuclide pair 36 for a theranostic approach. 37,38…”

“…25,26 In addition, the combination of the gamma emitter 131 Ba for diagnosis and both alpha emitters 223/224 Ra for therapy is beneficial and leads to a matched nuclide pair 36 for a theranostic approach. 37,38 Functionalized calix [4]crown ethers and their complexes with Ba 2+ and Ra 2+ are known from the literature, 24,[28][29][30]39,40 e.g., in environmental chemistry, but little is known about the complexation behaviour, the respective complex stability constants, and the in vivo behaviour of such complexes. In the past, the cavity size of calix [4]crown-6 was tested to fit best for heavier group 2 metals.…”

Extracellular vesicles deliver sodium iodide symporter protein and promote cancer cell radioiodine therapy

“…The search for more precise cancer diagnosis and treatment has led to interest in exploiting exosomes and EVs for tumor theranostics 11 , 12 . A major theranostic tool is radiopharmaceuticals that deliver radioactive particles to cancer cells for diagnostic imaging as well as to provide targeted radionuclide therapy 13 . Successful theranostic radionuclide therapy is crucially dependent on presence of abundant amounts of target molecules on the malignant cells.…”