Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [Lu]Lu-DOTATATE.

Purpose: Recent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL).

The Impact of Radiobiologically Informed Dose Prescription on the Clinical Benefit of Y SIRT in Colorectal Cancer Patients.

The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to Y. Twenty-three mCRC patients with liver metastases refractory to chemotherapy were included. Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method.

OpenDose: Open-Access Resource for Nuclear Medicine Dosimetry.

Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be performed using precomputed tables of specific absorbed fractions (SAFs) or S values based on dosimetric models. The aim of the OpenDose collaboration is to generate and make freely available a range of dosimetric data and tools.

Imaging DNA Damage Repair In Vivo After Lu-DOTATATE Therapy.

Molecular radiotherapy using Lu-DOTATATE is a most effective treatment for somatostatin receptor-expressing neuroendocrine tumors. Despite its frequent and successful use in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery. On positive uptake on octreotide-based PET/SPECT imaging, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry, or radiobiologic and DNA damage effects in the tumor.

Radiosensitivity of colorectal cancer to Y and the radiobiological implications for radioembolisation therapy.

Approximately 50% of all colorectal cancer (CRC) patients will develop metastasis to the liver. Y selective internal radiation therapy (SIRT) is an established treatment for metastatic CRC. There is still a fundamental lack of understanding regarding the radiobiology underlying the dose response.

Targeted Radionuclide Therapy: New Advances for Improvement of Patient Management and Response.

Compared to external beam radiotherapy, targeted radionuclide therapy (TRT) allows for systemic radiation treatment of metastatic lesions. Published work on recent strategies to improve patient management and response to TRT through individualising patient treatment, modifying treatment pharmacokinetics and increasing anticancer potency are discussed in this review, with a special focus on the application of clinically evaluated radiolabelled ligands and peptides in the treatment of neuroendocrine and prostate cancers.

Subcellular Targeting of Theranostic Radionuclides.

The last decade has seen rapid growth in the use of theranostic radionuclides for the treatment and imaging of a wide range of cancers. Radionuclide therapy and imaging rely on a radiolabeled vector to specifically target cancer cells. Radionuclides that emit β particles have thus far dominated the field of targeted radionuclide therapy (TRT), mainly because the longer range (μm-mm track length) of these particles offsets the heterogeneous expression of the molecular target.

Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values.

The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely Ga, Br, Zr, Nb, Tc, In, Sn, Sb, I, I, I, La, Pt and Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport.

A stochastic cascade model for Auger-electron emitting radionuclides.

To benchmark a Monte Carlo model of the Auger cascade that has been developed at the Australian National University (ANU) against the literature data. The model is applicable to any Auger-electron emitting radionuclide with nuclear structure data in the format of the Evaluated Nuclear Structure Data File (ENSDF). Schönfeld's algorithms and the BrIcc code were incorporated to obtain initial vacancy distributions due to electron capture (EC) and internal conversion (IC), respectively.

Strand breakage by decay of DNA-bound I provides a basis for combined PET imaging and Auger endoradiotherapy.

Purpose DNA ligands labelled with I induce cytotoxic DNA double-strand breaks (DSB), suggesting a potential for Auger endoradiotherapy. Since the 60-day half-life of I is suboptimal for therapy, we have investigated another Auger-emitter I, with shorter half-life (4.18 days), and the additional feature of positron-emission, enabling positron emission tomography (PET) imaging.