Advancing 6-bromo-7-[C]methylpurine to clinical use: improved regioselective radiosynthesis, non-clinical toxicity data and human dosimetry estimates.

Background: 6-Bromo-7-[C]methylpurine ([C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [C]BMP afforded a mixture of 7- and 9-[C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [C]BMP, the results of a non-clinical toxicity study as well as human dosimetry estimates based on mouse PET data.

Human Biodistribution and Radiation Dosimetry of the P-Glycoprotein Radiotracer [C]Metoclopramide.

Purpose: To assess in healthy volunteers the whole-body distribution and dosimetry of [C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier.

Procedures: Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images.

Dose Calculations and Dose-Effect Relationships in 177Lu-PSMA I&T Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer.

Unlabelled: Dose response of 22 patients experiencing mCRPC (metastatic castration-resistant prostate cancer) to Lu-PSMA I&T radionuclide therapy was investigated. Dosimetry calculations are used to assess correlations between dosimetric quantities and biomarker values.

Methods: The patients' age range was 74 ± 7 years at the time of the investigated treatment cycle, and the mean injected activity was 7416 ± 218 MBq.

Towards Improved Pharmacokinetic Models for the Analysis of Transporter-Mediated Hepatic Disposition of Drug Molecules with Positron Emission Tomography.

Positron emission tomography (PET) imaging with radiolabeled drugs holds great promise to assess the influence of membrane transporters on hepatobiliary clearance of drugs. To exploit the full potential of PET, quantitative pharmacokinetic models are required. In this study, we evaluated the suitability of different compartment models to describe the hepatic disposition of [C]erlotinib as a small-molecule model drug which undergoes transporter-mediated hepatobiliary excretion.

Retina dose as a predictor for visual acuity loss in Ru eye plaque brachytherapy of uveal melanomas.

Background And Purpose: To evaluate the retina dose as a risk factor associated with loss of visual acuity (VA) in Ru plaque brachytherapy.

Material/methods: 45 patients receiving Ru plaques brachytherapy (median follow-up 29.5 months) were included in this study.

Adaption of a PIN-diode detector as an online neutron monitor for the thermal column of the TRIGA research reactor.

A BNCT online neutron monitoring system was tested in a TRIGA reactor, using a silicon PIN-diode with a conversion foil. The setup was tested with different reactor powers at the hot and cold ends of the irradiation channel, using activation foils to compare with measured fluxes. The results demonstrate good reproducibility and show a linear correlation between signal of the PIN-diode and neutron flux at all positions, demonstrating this approach to be suitable for online monitoring of the neutron flux.

Treatment plan optimization and robustness of Ru eye plaque brachytherapy using a novel software tool.

Background And Purpose: To analyze treatment plan robustness and plan optimization strategies of Ru eye plaque brachytherapy using a novel software tool.

Materials And Methods: A treatment planning software was developed that allows to calculate dose-volume metrics. Plaque misplacements were simulated and evaluated with respect to the effect on tumor coverage and dose changes in critical structures.

On the applicability of [F]FBPA to predict L-BPA concentration after amino acid preloading in HuH-7 liver tumor model and the implication for liver boron neutron capture therapy.

Introduction: In recent years extra-corporal application of boron neutron capture therapy (BNCT) was evaluated for liver primary tumors or liver metastases. A prerequisite for such a high-risk procedure is proof of preferential delivery and high uptake of a B-pharmaceutical in liver malignancies. In this work we evaluated in a preclinical tumor model if [F]FBPA tissue distribution measured with PET is able to predict the tissue distribution of [B]L-BPA.

Whole-Body Distribution and Radiation Dosimetry of 11C-Elacridar and 11C-Tariquidar in Humans.

Unlabelled: (11)C-elacridar and (11)C-tariquidar are new PET tracers to assess the transport activity of P-glycoprotein (adenosine triphosphate-binding cassette subfamily B, member 1 [ABCB1]) and breast cancer resistance protein (adenosine triphosphate-binding cassette subfamily G, member 2 [ABCG2]). This study investigated the whole-body distribution and radiation dosimetry of both radiotracers in humans.

Methods: Twelve healthy volunteers (6 women, 6 men) underwent whole-body PET/CT imaging over the 90 min after injection of either (11)C-elacridar or (11)C-tariquidar.

PET image segmentation using a Gaussian mixture model and Markov random fields.

Background: Classification algorithms for positron emission tomography (PET) images support computational treatment planning in radiotherapy. Common clinical practice is based on manual delineation and fixed or iterative threshold methods, the latter of which requires regression curves dependent on many parameters.

Methods: An improved statistical approach using a Gaussian mixture model (GMM) is proposed to obtain initial estimates of a target volume, followed by a correction step based on a Markov random field (MRF) and a Gibbs distribution to account for dependencies among neighboring voxels.

Cellular uptake and in vitro antitumor efficacy of composite liposomes for neutron capture therapy.

Background: Neutron capture therapy for glioblastoma has focused mainly on the use of (10)B as neutron capture isotope. However, (157)Gd offers several advantages over boron, such as higher cross section for thermal neutrons and the possibility to perform magnetic resonance imaging during neutron irradiation, thereby combining therapy and diagnostics. We have developed different liposomal formulations of gadolinium-DTPA (Magnevist®) for application in neutron capture therapy of glioblastoma.

Confirmation of a realistic reactor model for BNCT dosimetry at the TRIGA Mainz.

Purpose: In order to build up a reliable dose monitoring system for boron neutron capture therapy (BNCT) applications at the TRIGA reactor in Mainz, a computer model for the entire reactor was established, simulating the radiation field by means of the Monte Carlo method. The impact of different source definition techniques was compared and the model was validated by experimental fluence and dose determinations.

Methods: The depletion calculation code origen2 was used to compute the burn-up and relevant material composition of each burned fuel element from the day of first reactor operation to its current core.

Relevance of PET for pretherapeutic prediction of doses in peptide receptor radionuclide therapy.

Personalized dosimetry in radionuclide therapy has gained much attention in recent years. This attention has also an impact on peptide receptor radionuclide therapy (PRRT). This article reviews the PET-based imaging techniques that can be used for pretherapeutic prediction of doses in PRRT.

Measurements of occupational and patient exposure as well as image quality for two C-arms.

Two different C-arms, a Philips Veradius and a Ziehm Vision FD were evaluated with regard to occupational and patient radiation exposure as well as image quality. For this, the scatter radiation, the entrance surface dose rate (ESD rate) and the low contrast detectability (LCD) were evaluated with regard to different examination modes, using phantoms with different thicknesses as well as a Leeds Test Object. The results show a large range of variance between the two systems in relation to the topics investigated.

Dose determination using alanine detectors in a mixed neutron and gamma field for boron neutron capture therapy of liver malignancies.

Unlabelled: Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and may be suitable for measurements in mixed neutron and gamma fields.

Dose calculation in biological samples in a mixed neutron-gamma field at the TRIGA reactor of the University of Mainz.

To establish Boron Neutron Capture Therapy (BNCT) for non-resectable liver metastases and for in vitro experiments at the TRIGA Mark II reactor at the University of Mainz, Germany, it is necessary to have a reliable dose monitoring system. The in vitro experiments are used to determine the relative biological effectiveness (RBE) of liver and cancer cells in our mixed neutron and gamma field. We work with alanine detectors in combination with Monte Carlo simulations, where we can measure and characterize the dose.

Discrete beta dose kernel matrices for nuclides applied in targeted radionuclide therapy (TRT) calculated with MCNP5.

Purpose: Radiopharmaceuticals administered in targeted radionuclide therapy (TRT) rely to a great extent not only on beta-emitting nuclides but also on emitters of monoenergetic electrons. Recent advances like combined PET/CT devices, the consequential coregistration of both data, the concept of using beta couples for diagnosis and therapy, respectively, as well as the development of voxel models offer a great potential for developing TRT dose calculation systems similar to those available for external beam treatment planning. The deterministic algorithms in question for this task are based on the convolution of three-dimensional matrices, one representing the activity distribution and the other the dose point kernel.

Diversification of existing reference phantoms in nuclear medicine: Calculation of specific absorbed fractions for 21 mathematical phantoms and validation through dose estimates resulting from the administration of (18)F-FDG.

Current dose assessment in nuclear medicine patient studies relies on published S-values, which are, in turn, based on calculated specific absorbed fractions (SAFs) available for a limited number of anthro-pomorphic computational phantoms. In order to take the individual physiognomy of patients more into account, this study aimed to broaden the supply of phantoms and their respective SAFs. An ensemble of 21 mathematical phantoms was submitted to the Monte Carlo Code MCNP4c2 for the purpose of calculation of SAFs for annihilation radiation.