[Yttrium-90-DOTA-Tyr(3)]-octreotide (DOTATOC) and [(177)Lu-DOTA-Tyr(3)-Thr(8)]-octreotide (DOTATATE) are used for peptide receptor-mediated radionuclide therapy (PRMRT) in neuroendocrine tumours. No human data comparing these two compounds are available so far. We used (111)In as a surrogate for (90)Y and (177)Lu and examined whether one of the (111)In-labelled peptides had a more favourable biodistribution in patients with neuroendocrine tumours. Special emphasis was given to kidney uptake and tumour-to-kidney ratio since kidney toxicity is usually the dose-limiting factor. Five patients with metastatic neuroendocrine tumours were injected with 222 MBq (111)In-DOTATOC and (111)In-DOTATATE within 2 weeks. Up to 48 h after injection, whole-body scans were performed and blood and urine samples were collected. The mean absorbed dose was calculated for tumours, kidney, liver, spleen and bone marrow. In all cases (111)In-DOTATATE showed a higher uptake (%IA) in kidney and liver. The amount of (111)In-DOTATOC excreted into the urine was significantly higher than for (111)In-DOTATATE. The mean absorbed dose to the red marrow was nearly identical. (111)In-DOTATOC showed a higher tumour-to-kidney absorbed dose ratio in seven of nine evaluated tumours. The variability of the tumour-to-kidney ratio was high and the significance level in favour of (111)In-DOTATOC was P=0.065. In five patients the pharmacokinetics of (111)In-DOTATOC and (111)In-DOTATATE was found to be comparable. The two peptides appear to be nearly equivalent for PRMRT in neuroendocrine tumours, with minor advantages for (111)In/(90)Y-DOTATOC; on this basis, we shall continue to use (90)Y-DOTATOC for PRMRT in patients with metastatic neuroendocrine tumours.

Various radionuclides have been proposed for systemic tumor therapy. However, in most dosimetric analysis of proposed radionuclides the charged particles are taken into consideration while the potential photons are ignored. The photons will cause undesirable irradiation of normal tissue, and increase the probability of toxicity in, e.g., the bone marrow. The aim of this study was to investigate the dosimetric properties according to particle range, photon emission, and subcellular radionuclide distribution, of a selection of radionuclides used or proposed for radionuclide therapy, and to investigate the possibility of dividing radionuclides into groups according to their dosimetric properties. The absorbed dose rate to the tumors divided by the absorbed dose rate to the normal tissue (TND) was estimated for different tumor sizes in a mathematical model of the human body. The body was simulated as a 70-kg ellipsoid and the tumors as spheres of different sizes (1 ng-100 g). The radionuclides were either assumed to be uniformly distributed throughout the entire tumor and normal tissue, or located in the nucleus or the cytoplasm of the tumor cells and on the cell membrane of the normal cells. Fifty-nine radionuclides were studied together with monoenergetic electrons, positrons, and alpha particles. The tumor and normal tissue were assumed to be of water density. The activity concentration ratio between the tumor and normal tissue was assumed to be 25. The radionuclides emitting low-energy electrons combined with a low photon contribution, and the alpha emitters showed high TND values for most tumor sizes. Electrons with higher energy gave reduced TND values for small tumors, while a higher photon contribution reduced the TND values for large tumors. Radionuclides with high photon contributions showed low TND value for all tumor sizes studied. The radionuclides studied could be divided into four main groups according to their TND values: beta emitters, Auger electron emitters, photon emitters, and alpha emitters. The TND values of the beta emitters were not affected by the subcellular distribution of the radionuclide. The TND values of the Auger electron emitters were affected by the subcellular radionuclide distribution. The photon emitters showed low TND values that were only slightly affected by the subcellular radionuclide distribution. The alpha emitters showed high TND values that were only slightly affected by the subcellular radionuclide distribution. This dosimetric characterization of radionuclides may be valuable in choosing the appropriate radionuclides for specific therapeutic applications.

Point kernels describe the energy deposited at a certain distance from an isotropic point source and are useful for nuclear medicine dosimetry. They can be used for absorbed-dose calculations for sources of various shapes and are also a useful tool when comparing different Monte Carlo (MC) codes. The aim of this study was to compare point kernels calculated by using the mixed MC code, PENELOPE (v. 2006), with point kernels calculated by using the condensed-history MC codes, ETRAN, GEANT4 (v. 8.2), and MCNPX (v. 2.5.0). Point kernels for electrons with initial energies of 10, 100, 500, and 1 MeV were simulated with PENELOPE. Spherical shells were placed around an isotropic point source at distances from 0 to 1.2 times the continuous-slowing-down-approximation range (R(CSDA)). Detailed (event-by-event) simulations were performed for electrons with initial energies of less than 1 MeV. For 1-MeV electrons, multiple scattering was included for energy losses less than 10 keV. Energy losses greater than 10 keV were simulated in a detailed way. The point kernels generated were used to calculate cellular S-values for monoenergetic electron sources. The point kernels obtained by using PENELOPE and ETRAN were also used to calculate cellular S-values for the high-energy beta-emitter, 90Y, the medium-energy beta-emitter, 177Lu, and the low-energy electron emitter, 103mRh. These S-values were also compared with the Medical Internal Radiation Dose (MIRD) cellular S-values. The greatest differences between the point kernels (mean difference calculated for distances, <0.9 r/R(CSDA)), using PENELOPE and those from ETRAN, GEANT4, and MCNPX, were 3.6%, 6.2%, and 14%, respectively. The greatest difference between the cellular S-values for monoenergetic electrons was 1.4%, 2.5%, and 6.9% for ETRAN, GEANT4, and MCNPX, respectively, compared to PENELOPE, if omitting the S-values when the activity was distributed on the cell surface for 10-keV electrons. The largest difference between the cellular S-values for the radionuclides, between PENELOPE and ETRAN, was seen for 177Lu (1.2%). There were large differences between the MIRD cellular S-values and those obtained from PENELOPE: up to 420% for monoenergetic electrons and <22% for the radionuclides, with the largest difference for 103mRh. In conclusion, differences were found between the point kernels generated by different MC codes, but these differences decreased when cellular S-values were calculated, and decreased even further when the energy spectra of the radionuclides were taken into consideration.

This protocol allows a precise pretherapeutic computation of the expected three-dimensional dose distribution and is clearly superior to the previously used dosimetry based on planar scintigraphic images. It has become an indispensable tool for planning intratumoural radiopeptide therapy in glioma patients.

Biokinetic data are important when calculating the absorbed dose to the patients and can also be used to find the optimal time between injection and imaging. To the authors' knowledge, there are no published biokinetic data in humans for (18)F-choline, except some distribution data at single time points. Four patients with suspicion of metastases due to biochemical recurrence (measurable prostate-specific antigen in plasma) after radical prostatectomy were injected with (18)F-choline. Four whole-body PET/CT images were taken with 1 h interval, starting immediately after injection. Blood samples were taken and all urine was collected for 3.5 h. The corrected decay activity content in the kidneys was 22-37 % higher immediately after injection when compared with the later time points. The highest activity concentration was found in kidneys (43 kBq ml(-1)). The organ with highest activity content was the liver (11 % of injected activity, % IA). Thirty minutes after the injection 4-16 % IA was left in the blood. Less than 9 % IA was excreted with the urine during the first 3.5 h after injection.