ABSTRACT
Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([123I]IAZA), to isotopes 131I (therapeutic) and 124I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [123I]IAZA were obtained previously. These data are used here to calculate residence times for 131I and 124I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131I and 124I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [124I]IAZA or therapeutic administration of [131I]IAZA.
ABSTRACT
PURPOSE: The response of well-type ionization chambers used, for example, in brachytherapy and nuclear medicine, depends on the location of the source. In cases where the source length is variable (typically in nuclear medicine), it is also dependent on length of the source. Here, the combined effect on chamber sensitivity of both source position and length is investigated in detail. This analysis is important if nominal values for source location and length are prescribed as (arbitrary but fixed) values in order to precisely define a chamber's sensitivity. During measurement, the actual values for source location and length can deviate from the nominal ones, altering sensitivity and thus giving rise to measurement uncertainties which, in turn, directly affect the doses administered to patients. Our aim is to investigate these uncertainties and minimize them with an optimized ion chamber design. METHODS: An analytical model for the chamber response is used to describe the variation of chamber sensitivity with respect to the two parameters, source position and length. The influence of the relative magnitude of uncertainty in both parameters is also accounted for. The effect of their combined variation on chamber sensitivity is required to be minimal and, employing differential geometry tools, a relationship is derived between them and the optimal height of the ionization chamber's sensitive volume. RESULTS: This relationship provides the chamber height h which minimizes its response variation for given nominal value of source location (quantified as insertion depth d) and prescribed source length l: h=2d-ρ(ρ)l, where ρ = δd/δl is defined as the quotient of uncertainty in insertion depth, δd, and uncertainty in source length, δl, and ρρ=4/9+ρ21+4ρ2, so that the optimal ionization chamber length varies between h=2d-12l and h=2d-23l. Alternatively, if h is given, suitable combinations of d and l can be deduced. CONCLUSIONS: The analysis presented here provides a tool for reducing the uncertainty budget of any cylindrically designed ionization chambers utilized for measuring extended on-axis sources. In particular, these results can be applied to a calibration-type ionization chamber design recently proposed for the cross-calibration of unsealed radionuclides.
ABSTRACT
6-Deoxy-6-[(18)F]fluoro-D-fructose (6-[(18)F]FDF) is a promising PET radiotracer for imaging GLUT5 in breast cancer. The present work describes GMP synthesis of 6-[(18)F]FDF in an automated synthesis unit (ASU) and dosimetry calculations to determine radiation doses in humans. GMP synthesis and dosimetry calculations are important prerequisites for first-in-human clinical studies of 6-[(18)F]FDF. The radiochemical synthesis of 6-[(18)F]FDF was optimized and adapted to an automated synthesis process using a Tracerlab FXFN ASU (GE Healthcare). Starting from 30 GBq of cyclotron-produced n.c.a. [(18)F]fluoride, 2.9 ± 0.1 GBq of 6-[(18)F]FDF could be prepared within 50 min including HPLC purification resulting in an overall decay-corrected radiochemical yield of 14 ± 3% (n = 11). Radiochemical purity exceeded 95%, and the specific activity was greater than 5.1 GBq/µmol. Sprague-Dawley rats were used for biodistribution experiments, and dynamic and static small animal PET experiments. Biodistribution studies served as basis for allometric extrapolation to the standard man anatomic model and normal organ-absorbed dose calculations using OLINDA/EXM software. The calculated human effective dose for 6-[(18)F]FDF was 0.0089 mSv/MBq. Highest organ doses with a dose equivalent of 0.0315 mSv/MBq in a humans were found in bone. Injection of 370 MBq (10 mCi) of 6-[(18)F]FDF results in an effective whole body radiation dose of 3.3 mSv in humans, a value comparable to that of other (18)F-labeled PET radiopharmaceuticals. The optimized automated synthesis under GMP conditions, the good radiochemical yield and the favorable human radiation dosimetry estimates support application of 6-[(18)F]FDF in clinical trials for molecular imaging of GLUT5 in breast cancer patients.[This corrects the article on p. 248 in vol. 4.].
ABSTRACT
6-Deoxy-6-[(18)F]fluoro-D-fructose (6-[(18)F]FDF) is a promising PET radiotracer for imaging GLUT5 in breast cancer. The present work describes GMP synthesis of 6-[(18)F]FDF in an automated synthesis unit (ASU) and dosimetry calculations to determine radiation doses in humans. GMP synthesis and dosimetry calculations are important prerequisites for first-in-human clinical studies of 6-[(18)F]FDF. The radiochemical synthesis of 6-[(18)F]FDF was optimized and adapted to an automated synthesis process using a Tracerlab FXFN ASU (GE Healthcare). Starting from 30 GBq of cyclotron-produced n.c.a. [(18)F]fluoride, 2.9 ± 0.1 GBq of 6-[(18)F]FDF could be prepared within 50 min including HPLC purification resulting in an overall decay-corrected radiochemical yield of 14 ± 3% (n = 11). Radiochemical purity exceeded 95%, and the specific activity was greater than 5.1 GBq/µmol. Sprague-Dawley rats were used for biodistribution experiments, and dynamic and static small animal PET experiments. Biodistribution studies served as basis for allometric extrapolation to the standard man anatomic model and normal organ-absorbed dose calculations using OLINDA/EXM software. The calculated human effective dose for 6-[(18)F]FDF was 0.0089 mSv/MBq. Highest organ doses with a dose equivalent of 0.0315 mSv/MBq in a humans were found in bone. Injection of 370 MBq (10 mCi) of 6-[(18)F]FDF results in an effective whole body radiation dose of 3.3 mSv in humans, a value comparable to that of other (18)F-labeled PET radiopharmaceuticals. The optimized automated synthesis under GMP conditions, the good radiochemical yield and the favorable human radiation dosimetry estimates support application of 6-[(18)F]FDF in clinical trials for molecular imaging of GLUT5 in breast cancer patients.
ABSTRACT
Post-implant dosimetry for permanent prostate brachytherapy is typically performed using computed tomography (CT) images, for which the clear visualization of soft tissue structures is problematic. Registration of CT and magnetic resonance (MR) image volumes can improve the definition of all structures of interest (soft tissues, bones, and seeds) in the joint image set. In the present paper, we describe a novel two-stage rigid-body registration algorithm that consists of (1) parallelization of straight lines fit to image features running primarily in the superior-inferior (Z) direction, followed by (2) normalized mutual information registration. The first stage serves to fix rotation angles about the anterior-posterior (Y) and left-right (X) directions, and the second stage determines the remaining Z-axis rotation angle and the X, Y, Z translation values. The new algorithm was applied to CT and 1.5T MR (T2-weighted and balanced fast-field echo sequences) axial image sets for three patients acquired four weeks after prostate brachytherapy using 125I seeds. Image features used for the stage 1 parallelization were seed trains in CT and needle tracks and seed voids in MR. Simulated datasets were also created to further investigate algorithm performance. Clinical image volumes were successfully registered using the two-stage approach to within a root-mean-squares (RMS) distance of <1.5 mm, provided that some pubic bone and anterior rectum were included in the registration volume of interest and that no motion artifact was apparent. This level of accuracy is comparable to that obtained for the same clinical datasets using the Procrustes algorithm. Unlike Procrustes, the new algorithm can be almost fully automated, and hence we conclude that its further development for application in post-implant dosimetry is warranted.
