Renaud Lhommel

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.

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.

MRI for response assessment in metastatic bone disease

AbstractBackgroundBeyond lesion detection and characterisation, and disease staging, the quantification of the tumour load and assessment of response to treatment are daily expectations in oncology.MethodsBone lesions have been considered “non-measurable” for years as opposed to lesions involving soft tissues and “solid” organs like the lungs or liver, for which response evaluation criteria are used in every day practice. This is due to the lack of sensitivity, specificity and measurement capabilities of imaging techniques available for bone assessment, i.e. skeletal scintigraphy (SS), radiographs and computed tomography (CT).ResultsThis paper reviews the possibilities and limitations of these techniques and highlights the possibilities of positron emission tomography (PET), but mainly concentrates on magnetic resonance imaging (MRI).ConclusionPractical morphological and quantitative approaches are proposed to evaluate the treatment response of bone marrow lesions using “anatomical” MRI. Recent developments of MRI, i.e. dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI), are also covered.Key Points• MRI offers improved evaluation of skeletal metastases and their response to treatment. • This new indication for MRI has wide potential impact on radiological practice. • MRI helps meet the expectations of the oncological community. • We emphasise the practical aspects, with didactic cases and illustrations.

Diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease: attributes and limitations of the current modalities

Cyst infection is a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD) because of the lack of specific manifestations and limitations of conventional imaging procedures. Still, recent clinical observations and series have highlighted common criteria for this condition. Cyst infection is diagnosed if confirmed by cyst fluid analysis showing bacteria and neutrophils, and as a probable diagnosis if all four of the following criteria are concomitantly met: temperature of >38°C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dL and no evidence for intracystic bleeding on computed tomography (CT). In addition, the elevation of serum carbohydrate antigen 19-9 (CA19-9) has been proposed as a biomarker for hepatic cyst infection. Positron-emission tomography after intravenous injection of 18-fluorodeoxyglucose, combined with CT, proved superior to radiological imaging techniques for the identification and localization of kidney and liver pyocyst. This review summarizes the attributes and limitations of these recent clinical, biological and imaging advances in the diagnosis of cyst infection in patients with ADPKD.

Quantitative and qualitative analysis of metabolic response at interim positron emission tomography scan combined with International Prognostic Index is highly predictive of outcome in diffuse large B-cell lymphoma

Abstract The prognostic value of interim 18fluorodeoxyglucose positron emission tomography (i-PET) was investigated in 73 patients (median age 60 years) with diffuse large B-cell lymphoma (DLBCL). i-PET was analyzed using the Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Patients with a DS of 1–3 demonstrated a significantly (p < 0.0001) better outcome (median follow-up 2.4 years) than patients with a score of 4 or 5 in terms of event-free survival (EFS) (79% vs. 36%), progression-free survival (PFS) (84% vs. 47%) and overall survival (OS) (91% vs. 51%). EFS (73% vs. 42%), PFS (78% vs. 50%) and OS (88% vs. 56%) were also significantly (p = 0.023) different between patients with ΔSUVmax > 66% or ≤ 66%. Patients (n = 33) combining a favorable age-adjusted International Prognostic Index (IPI) (0 or 1) and a negative i-PET either by DS or ΔSUVmax criteria showed a particularly good outcome (EFS: 85%, PFS: 88%, OS: 94%). Overall, i-PET was highly and independently predictive of any outcome, and its negative predictive value was improved by combination with IPI.

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.

Hemoglobin level significantly impacts the tumor cell survival fraction in humans after internal radiotherapy

BackgroundAnemia is usually not taken into account in internal radiotherapy. We investigated whether the hemoglobin (Hb) level could have an impact on the tumor response, as observed in external beam radiotherapy (EBRT).MethodsAbsorbed doses of 25 hepatic metastatic sites in eight patients who underwent a liver selective internal radiotherapy (SIRT) were computed by a 3D convolution of a dose deposition kernel with the 90Y time-of-flight positron emission tomography (TOF-PET) images acquired following therapy. Early tumor response was assessed by comparing a follow-up FDG TOF-PET scan with a baseline scan. Hb level was measured on the day of the SIRT procedure.ResultsAll patients displayed early tumor response increasing with the tumor-absorbed dose. Significant differences between patients were noted, the response slope correlating with the Hb level. After applying a global fit on all metastases using a tumor radiosensitivity modulated by a Hb enhancement factor (HEF) linearly dependent on the Hb level, a strong correlation (R = 0.96) was observed between the early response and the absorbed dose. Hb level had a major impact on tumor response by modulating HEF by a factor 6.ConclusionsThese results prove the significant impact of Hb level on the tumor response and support the study of methods for correcting tumor hypoxia, such as intensively performed in EBRT. The quantitative analysis of the relationship between tumor doses and early response has the power to allow fast screening of such correction methods in limited patient series. Internal radiotherapy could be more efficient if performed earlier in the therapy line, when the disease- and treatment-related anemia remains limited.

Classification of Non-Demented Patients Attending a Memory Clinic using the New Diagnostic Criteria for Alzheimer's Disease with Disease-Related Biomarkers

BACKGROUND New diagnostic criteria for predemential Alzheimers disease (AD) advocate the use of biomarkers. However, the benefit of using biomarkers has not been clearly demonstrated in clinical practice. OBJECTIVE To investigate whether a combination of biomarkers may be helpful in classifying a population of non-demented patients attending a Memory Clinic. METHODS Sixty non-demented patients were compared with 31 healthy elderly subjects. All subjects underwent a neuropsychological examination, brain 3T magnetic resonance imaging, [F18]-fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According to their performance on memory, language, executive, and visuo-spatial domains, the patients were classified as mild cognitive impairment (amnestic, non-amnestic, single, or multiple domain) or subjective cognitive impairment. Patients were then classified according to the National Institute on Aging-Alzheimers Association (NIA-AA) criteria, using the normalized mean hippocampal volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of truth was the clinical status at study entry (patient versus control). RESULTS The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA criteria were applicable in 85% of patients and 87% of controls. For biomarkers the best sensitivity (72%) at a fixed specificity of 84% was achieved by a combination of the three biomarkers. The clinical diagnosis was reconsidered in more than one third of the patients (42%) as a result of including the biomarker results. CONCLUSIONS Application of the new NIA-AA AD diagnostic criteria based on biomarkers in an unselected sample of non-demented patients attending a Memory Clinic was useful in allowing for a better classification of the subjects.