Response assessment of somatostatin receptor targeted radioligand therapies for progressive intracranial meningioma.

BACKGROUND: In somatostatin receptor (SSTR) expressing progressive meningioma, peptide receptor radionuclide therapy (PRRT) has shown effect in small clinical series. However, standardized treatment and response assessment protocols are lacking. We present our experience on PPRT with 177Lu-DOTATATE in progressive meningioma with a special emphasis on state-of-the-art response assessment. METHODS: Retrospective analysis on PRRT with 177Lu-DOTATATE from 2015 to 2019. Pre- and post-therapy imaging was performed using MRI and 68Ga-DOTATATE-PET for standard bidimensional and volumetric analyses, respectively, following novel RANO guidelines. RESULTS: Seven patients with progressive intracranial meningioma (median age 73 years, interquartile range 60-76; 5 WHO II, 2 WHO I; 5 multifocal) received a median of 4 cycles 2 3 4 of PRRT with 177Lu-DOTATATE in eight-week intervals. Three patients did not undergo post-therapy 68Ga-DOTATATE-PET due to early symptomatic progression and subsequent cessation of PRRT. After completion of 4 PRRT cycles volumetric PET imaging showed stable disease in two of four patients. According to bidimensional MRI response assessment, only one patient was stable. Progression free survival at six months was 42.9 %. CONCLUSION: In this heterogeneous collective of seven patients with progressive meningioma, 177Lu-DOTATATE therapies showed heterogeneous effectiveness. PET-based volumetric assessment should be used for response assessment in PRRT additionally to bidimensional imaging.

Isochronous assessment of cardiac metabolism and function in mice using hybrid PET/MRI.

UNLABELLED: Recently, integrated small-animal PET/MRI prototypes that provide isochronous and coregistered datasets of morphology and function through the simultaneous acquisition of PET and MRI data have been developed. However, the need for MRI compatibility can constrain the technical design of the PET components and may lead to a lower sensitivity and lower spatial and temporal resolutions. The aim of this study was to evaluate the suitability of a prototype preclinical PET/MRI system for the simultaneous assessment of cardiac metabolism and function in mice. A stand-alone high-resolution small-animal PET scanner using the same evaluation protocols was used as a reference. METHODS: Simultaneous PET/MR images of an infarct mouse model (21 animals plus 3 controls) were acquired. The imaging performance of the MRI-compatible PET insert was evaluated with respect to count sensitivity; myocardium-to-background contrast; suitability for the analysis of global left ventricular function; and uptake difference in scar, border-zone, and remote regions. The radiotracer (18)F-FDG was used to acquire cardiac gated PET data, applying retrospective coincidence sorting. The PET insert data were coregistered to the MR images by determination of the appropriate transformation matrix. RESULTS: An optimal registration of PET and MR images from the integrated system was achieved, and the reconstructed images showed a good visual correspondence in infarct areas between PET and MRI data. As expected, the PET insert showed a poorer performance with respect to counting rate and myocardium-to-background ratio than did the high-resolution PET. Assessment of left ventricular volumes was possible with the current PET/MRI prototype. A good correlation was found between PET and MRI (R > 0.95). Local PET uptake was successfully determined for different tissue, and a differentiation among remote, border-zone, and scar tissue was possible. However, the uptake difference for the PET/MRI prototype was lower than that for the high-resolution stand-alone PET system. CONCLUSION: A hybrid PET/MRI prototype was successfully used to assess cardiac parameters in an infarct mouse model, although performance was reduced when compared with a high-resolution animal PET scanner. Future technical improvements are expected to result in comparable performance while providing higher registration accuracy.

Assessment of infarct size by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose: a new absolute threshold technique.

Along with hibernating myocardium, infarct size is a critical term in the progression of left ventricular remodelling and congestive heart failure. Both infarcted and hibernating myocardium determine changes in remote non-ischaemic tissue. This study was designed to test the accuracy of a new technique to quantify infarct size using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG). Studies were carried out in (a) nine pigs with acute myocardial infarction (two sham-operated), produced by a 90-min occlusion of the circumflex coronary artery followed by a 4-h reperfusion, and (b) humans (six patients with ischaemic cardiomyopathy awaiting cardiac transplantation and five normal volunteers). In both animals and patients, myocardial FDG uptake was measured by PET during hyperinsulinaemic-euglycaemic clamp. Infarct size was quantified by an absolute threshold of tracer uptake obtained from the parametric (voxel-by-voxel) image of the metabolic rate of FDG. PET infarct size estimates were compared with independent ex vivo planimetric measurements of the explanted swine and patient hearts (at transplantation) after staining with triphenyltetrazolium chloride. There was good agreement between the planimetric and PET infarct size estimates both in pigs (n=9; r=0.96, v=0.94x+0.64, SEE=0.10, P<0.0001) and in humans (n=11; r=0.94, y=0.72x+2.93, SEE=0.09, P<0.0001). This study demonstrates the feasibility and accuracy of this PET method in estimating infarct size both in a model of reperfused acute myocardial infarction and in chronic ischaemic cardiomyopathy, although larger studies are needed to confirm these findings.