Stephan Walrand

Yttrium-90 TOF PET scan demonstrates high-resolution biodistribution after liver SIRT

The decay of Y has a minor branch to the 0 excited state [1], followed by an internal ee creation which happens in 32 out of one million decays [2]. Consequently, Y PET scan was proposed in order to assess the biodistribution [3] of Y-labelled therapeutic agents. A 61-year-old woman was referred for treatment of chemorefractory colorectal liver metastasis. Based on the pretreatment evaluation (including a diagnostic FDG PET/CT scan on day 1, and a prophylactic embolization of the right gastric and gastroduodenal arteries followed by a Tc-MAA SPECT/CT scan on day 8), 1.3 GBq of Y-labelled SIR-Spheres were administered by sequential catheterization of both liver lobes (day 15). Subsequently, a 30-min Y TOF PET/CT scan was performed using a Philips GEMINI TF camera. In order to prevent saturation of the detectors, a copper ring of 2.5 mm thickness was inserted into the gantry to absorb the bremsstrahlung x-rays. The TOF data were reconstructed with attenuation and scatter correction using Philips RAMLA software (eight iterations, three subsets). An additional 20 min bremsstrahlung Y-SPECT was acquired using a Trionix XLT20 triple head camera (medium energy collimator, 30% window centred on 90 keV). Data were reconstructed using OSEM (four iterations, six subsets). As illustrated, despite the differences in their respective uptake mechanism, Y-PET better reflects the tumour heterogeneity assessed by FDG PET/CT (a necrotic core surrounded by active tumour margins) than traditional bremsstrahlung Y-SPECT. This gain in resolution should therefore contribute to increasing the accuracy of the dose distribution into the tumours and their surrounding healthy tissues.

Feasibility of 90Y TOF PET-based dosimetry in liver metastasis therapy using SIR-Spheres

Purpose90Y-labelled compounds used in targeted radiotherapy are usually imaged with SPECT by recording the bremsstrahlung X-rays of the β decay. The continuous shape of the X-ray spectrum induces the presence of a significant fraction of scatter rays in the acquisition energy window, reducing the accuracy of biodistribution and of dosimetry assessments.MethodsThe aim of this paper is to use instead the low branch of e− e+ pair production in the 90Y decay. After administration of 90Y-labelled SIR-Spheres by catheterization of both liver lobes, the activity distribution is obtained by 90Y time-of-flight (TOF) PET imaging. The activity distribution is convolved with a dose irradiation kernel in order to derive the regional dosimetry distribution.ResultsEvaluation on an anatomical phantom showed that the method provided an accurate dosimetry assessment. Preliminary results on a patient demonstrated a high-resolution absorbed dose distribution with a clear correlation with tumour response.ConclusionThis supports the implementation of 90Y PET in selective internal radiation therapy of the liver.

Intragastric distribution of a standardized meal in health and functional dyspepsia: correlation with specific symptoms.

Abstract  In functional dyspepsia, abnormal intragastric distribution of a test meal has been identified but has never been correlated to any symptom pattern. The aim of this study was to compare the intragastric distribution of a meal between functional dyspepsia patients and controls, and to correlate distribution with symptom patterns, using scintigraphic gastric emptying studies. In forty patients with functional dyspepsia and 29 healthy volunteers, scintigraphic planar images were obtained immediately after ingestion of a mixed radiolabelled test meal and every 20 min for 2 h. The images of the stomach were divided into proximal and distal compartments. The mean intragastric distribution was similar in patients and controls. Over the whole test, 18 (45%) and 20 (50%) patients had a distal redistribution of the solid and liquid phase of the meal, respectively, while proximal retention of these phases was found in 13 (33%) and 9 (23%) patients. Early satiety was associated with early distal redistribution of the liquid phase and fullness was associated with late proximal retention. This study shows similar intragastric distribution of a test meal in health and functional dyspepsia. Within the patient group, an association between abnormal intragastric distribution patterns and symptom profiles was found, which might be related to different pathophysiological mechanisms.

Simultaneous correction of attenuation and distance-dependent resolution in SPECT: an analytical approach

An approximate analytical solution of the problem of attenuation and distance-dependent resolution effects in single photon emission tomography is presented for the case of a uniform absorbing medium. The algorithm obtained is a generalization of the Bellini and co-workers formula correcting for the single attenuation effect and is derived by means of Fourier transforms only. The method has been validated on mathematical phantoms as well as on physical data.

Dosimetry of yttrium-labelled radiopharmaceuticals for internal therapy: 86Y or 90Y imaging?

This paper reviews issues concerning 86Y positron emission tomography (PET), 90Y PET and 90Y bremsstrahlung imaging. Specific methods and corrections developed for quantitative imaging, for application in preclinical and clinical studies, and to assess 90Y dosimetry are discussed. The potential imaging capabilities with the radioisotopes 87Y and 88Y are also considered. Additional studies required to assess specific unaddressed issues are also identified.

Experimental facts supporting a red marrow uptake due to radiometal transchelation in 90Y-DOTATOC therapy and relationship to the decrease of platelet counts.

PurposeThe aim of this study was to retrospectively evaluate whether the red marrow (RM) takes up 111In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide and 86Y-DOTATOC and to assess the correlation between the RM absorbed doses and platelet count reduction as a biological dose estimate.MethodsData from 12 patients who underwent at 24 h p.i. high statistics 111In single photon emission computed tomography (SPECT) and 86Y positron emission tomography (PET) acquisitions of the chest were analysed. Uptake was measured on >7 cm spine length and converted to total RM uptake using standard RM distribution in man. RM absorbed doses were calculated assuming specific RM uptake and using the plasma and remainder of the body models. RM doses were correlated with the platelet count reduction at 4 weeks. In vitro experiments explored the metabolism of 111In-DTPA-D-Phe1-octreotide and 90Y-DOTATOC in plasma.ResultsThe correlation between the uptake of both tracers was excellent (R = 0.80), indicating that RM uptake of 86Y-DOTATOC reflects a real physiological process and not reconstruction artefacts. The kinetics of 86Y-DOTATOC RM activity was different than that in blood and tumours, with no activity at 4 h p.i. indicating that the uptake is not somatostatin receptor dependent. In vitro experiments showed a transchelation of both radiometals to free transferrin that could explain the RM uptake. In patients without chemotherapy and with a normal platelet count recovery, a good correlation (R = 0.96) was found between the RM doses and the platelet count reduction at the nadir.ConclusionThese experimental facts support the existence of a true RM uptake likely related to transchelation of the radiometal to transferrin. RM uptake correlates well with the observed acute RM toxicity.

Comparison of yttrium-90 quantitative imaging by TOF and non-TOF PET in a phantom of liver selective internal radiotherapy

The aim of this study is to determine the feasibility of achieving quantitative measurement in (90)Y-microspheres liver selective internal radiotherapy (SIRT) by imaging (90)Y with a conventional non-time of flight (TOF) PET device. Instead of the bremsstrahlung x-rays of the β-decay, the low branch of e(-)- e(+) pair production in the (90)Y-decay was used. The activity distribution in a phantom-simulated liver SIRT was obtained by direct (90)Y-PET imaging. We tested a LYSO TOF PET and two GSO and BGO non-TOF PET scanners using a 3.6-l cylindrical phantom filled with the (90)Y solution containing two sets of hot and cold spheres. The best hot contrast was obtained with the LYSO TOF. It was close to the expected value and remained constant, even for short acquisition times. The LYSO non-TOF was about 10% lower. The GSO performed similarly but degraded for shorter times whilst the BGO was the worst with 40% loss. For the cold spheres, the LYSO TOF and the GSO provided the best results, while the LYSO non-TOF and the BGO were the worst. (90)Y PET imaging in liver SIRT is achievable with LYSO TOF. Conventional LYSO and GSO show a loss of contrast and require longer acquisition times. BGO imaging is not feasible for dosimetry calculation.

4-Step Renal Dosimetry Dependent on Cortex Geometry Applied to 90Y Peptide Receptor Radiotherapy: Evaluation Using a Fillable Kidney Phantom Imaged by 90Y PET

Accurate dosimetry in 90Y peptide receptor radionuclide therapy (PRRT) helps to optimize the injected activity, to prevent kidney or red marrow toxicity, while giving the highest absorbed dose to tumors. The aim of this study was to evaluate whether direct 90Y bismuth germanate or lutetium yttrium orthosilicate time-of-flight PET was accurate enough to provide dosimetry estimates suitable to 90Y PRRT. Method: To overcome the statistical uncertainty arising from the low 90Y positron counting rate, the computation of the cortex mean-absorbed dose was divided into 4 steps: delineation of the cortex volume of interest (VOI) on the CT scan, determination of the recovery coefficient from the cortex VOI using the point-spread function of the whole imaging process, determination of the mean cortex-absorbed dose per unit cumulated activity in the cortex (Scortex←cortex value) from the cortex VOI using a 90Y voxel S value kernel, and determination of the number of decays in the cortex VOI from the PET reconstruction. Our 4-step method was evaluated using an anthropomorphic abdominal phantom containing a fillable kidney phantom based on the MIRD kidney model. Vertebrae with an attenuation similar to that of bone were also modeled. Two tumors were modeled by 7-mL hollow acrylic spheres and the spleen by a plastic bag. Activities corresponded to typical tissue uptake in a first 90Y-DOTATOC cycle of 4.4 GBq, considered as free of significant renal toxicity. Eight successive 45-min scans were acquired on both systems. Results: Both PET systems were successful in determining absorbed dose to modeled tumors but failed to provide accurate red marrow dosimetry. Renal cortex dosimetry was reproducible for both PET systems, with an accuracy of 3% for the bismuth germanate system but only 18% for the lutetium yttrium orthosilicate time-of-flight system, which was hindered by the natural radioactivity of the crystal, especially in the most attenuated area of the kidney. Conclusion: This study supports the use of direct 90Y PET of the first PRRT cycle to assess the kidney-absorbed dose and optimize the injected activity of the following cycles.

The Low Hepatic Toxicity per Gray of 90Y Glass Microspheres Is Linked to Their Transport in the Arterial Tree Favoring a Nonuniform Trapping as Observed in Posttherapy PET Imaging

90Y resin and glass microsphere liver radioembolizations delivering lobar doses of 70 and 120 Gy, respectively, display hepatic toxicity similar to 40-Gy fractionated external-beam radiotherapy. We investigated how the lower number of glass microspheres could induce a sufficiently nonuniform dose distribution explaining this paradox. Methods: Microscale dosimetry was assessed in the realistic liver model developed by Gulec et al. but using the Russell’s dose deposition kernel. A lattice of hexagonal prisms represented the hepatic lobules. Two hepatic arterial tree models—that is, a fixed-length and a variable-branches length—were used for the microsphere transport. Equal or asymmetric microsphere relative-spreading probability between 2 daughter vessels was assumed. Several 120-Gy liver simulations were performed: periodic simulations, where 1 or 6 glass microspheres were trapped in all and in only 1 of 6 portal tracts, respectively, and random simulations, where glass microsphere trapping assumed an equal probability for all the portal tracts or a variable probability depending on the successions of artery connections leading to the portal tract, both for the 2 arterial tree models. Results: For the 2 uniform simulations, all hepatic structures received at least 100 Gy. The fast decrease of the 90Y kernel as the inverse of the square of the distance r is counterbalanced by the number of contributing lobules containing microspheres that increases as r2. The random simulation with equal-spreading probability gave for the less irradiated tissue a lobule dose distribution centered around 103 Gy (full width at half maximum, 20 Gy). The distribution became significantly asymmetric with the 60%–40% relative-spreading probability, with a shift of the maximum from 103 down to 50 Gy, and about 17% of the lobules got a dose lower than 40 Gy to their different structures. Conclusion: The large nonuniform trapping produced by the microsphere transport in the arterial tree jointly with the low number of injected glass microspheres begins to explain their lower hepatic toxicity per Gray. In addition, the nonuniform trapping supports the fact that the granular aspect of 90Y PET imaging observed in patients could represent some reality and not only statistical noise.

Yttrium-90-labeled microsphere tracking during liver selective internal radiotherapy by bremsstrahlung pinhole SPECT: Feasibility study and evaluation in an abdominal phantom

BackgroundThe purpose of the study is to evaluate whether a pinhole collimator is better adapted to bremsstrahlung single photon emission computed tomography [SPECT] than parallel-hole collimators and in the affirmative, to evaluate whether pinhole bremsstrahlung SPECT, including a simple model of the scatter inside the patient, could provide a fast dosimetry assessment in liver selective internal radiotherapy [SIRT].Materials and methodsBremsstrahlung SPECT of an abdominal-shaped phantom including one cold and five hot spheres was performed using two long-bore parallel-hole collimators: a medium-energy general-purpose [MEGP] and a high-energy general-purpose [HEGP], and also using a medium-energy pinhole [MEPH] collimator. In addition, ten helical MEPH SPECTs (acquisition time 3.6 min) of a realistic liver-SIRT phantom were also acquired.ResultsWithout scatter correction for SPECT, MEPH SPECT provided a significantly better contrast recovery coefficient [CRC] than MEGP and HEGP SPECTs. The CRCs obtained with MEPH SPECT were still improved with the scatter correction and became comparable to those obtained with positron-emission tomography [PET] for the 36-, 30- (cold), 28-, and 24-mm-diameter spheres: CRC = 1.09, 0.59, 0.91, and 0.69, respectively, for SPECT and CRC = 1.07, 0.56, 0.84, and 0.63, respectively, for PET. However, MEPH SPECT gave the best CRC for the 19-mm-diameter sphere: CRC = 0.56 for SPECT and CRC = 0.01 for PET. The 3.6-min helical MEPH SPECT provided accurate and reproducible activity estimation for the liver-SIRT phantom: relative deviation = 10 ± 1%.ConclusionBremsstrahlung SPECT using a pinhole collimator provided a better CRC than those obtained with parallel-hole collimators. The different designs and the better attenuating material used for the collimation (tungsten instead of lead) explain this result. Further, the addition of an analytical modeling of the scattering inside the phantom resulted in an almost fully recovered contrast. This fills the gap between the performance of90Y-PET and bremsstrahlung pinhole SPECT which is a more affordable technique and could even be used during the catheterization procedure in order to optimize the90Y activity to inject.