Correction to: FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

The original version of this article, published on 6 July 2018, unfortunately contained a mistake.

FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

OBJECTIVES: To determine the value of 18F-FDG-PET/MRI in the diagnosis and management of patients with pelvic recurrence of rectal cancer. METHODS: Forty-four patients (16 women, 28 men) with a history of rectal cancer who received FDG-PET/MRI between June 2011 and February 2017 at our institution were retrospectively enrolled. Three patients received two FDG-PET/MRIs; thus a total of 47 examinations were included. Pelvic recurrence was confirmed either with histology (n = 27) or imaging follow-up (n = 17) (> 4 months). Two readers (one radiologist, one nuclear medicine physician) interpreted the images in consensus. Pelvic lesions were assessed regarding FDG uptake and morphology. Sensitivity, specificity, positive and negative predictive values as well as accuracy of PET/MRI in detecting recurrence were determined. RESULTS: In 47 FDG-PET/MRIs 30 suspicious pelvic lesions were identified, 29 of which were malignant. Two patients underwent resection and had histologically proven pelvic recurrence without showing suspicious findings on FDG-PET/MRI. Changes in management due to FDG-PET/MRI findings had been implemented in eight patients. Eighty per cent (16/20) of resected patients had histologically negative resection margins (R0), one patient had uncertain resection margins. Sensitivity of FDG-PET/MRI in detecting recurrence was 94%, specificity 94%, positive/negative predictive value and accuracy were 97%, 90% and 94%, respectively. CONCLUSIONS: FDG-PET/MRI is a valuable tool in the diagnosis and staging of pelvic recurrence in patients with rectal cancer. KEY POINTS: • Metabolic information obtained from PET coupled with excellent soft tissue contrast from MRI could facilitate detection of rectal cancer recurrence and assist in treatment planning. • PET/MRI demonstrates high sensitivity and specificity for the diagnosis of local recurrence of rectal cancer • PET/MRI led to alterations in management in 18.2% of patients.

Feasibility and performance of novel software to quantify metabolically active volumes and 3D partial volume corrected SUV and metabolic volumetric products of spinal bone marrow metastases on 18F-FDG-PET/CT.

Our aim was to assess feasibility and performance of novel semi-automated image analysis software called ROVER to quantify metabolically active volume (MAV), maximum standardized uptake value-maximum (SUV(max)), 3D partial volume corrected mean SUV (cSUV(mean)), and 3D partial volume corrected mean MVP (cMVP(mean)) of spinal bone marrow metastases on fluorine-18 fluorodeoxyglucose-positron emission tomography/computerized tomography ((18)F-FDG-PET/CT). We retrospectively studied 16 subjects with 31 spinal metastases on FDG-PET/CT and MRI. Manual and ROVER determinations of lesional MAV and SUV(max), and repeated ROVER measurements of MAV, SUV(max), cSUV(mean) and cMVP(mean) were made. Bland-Altman and correlation analyses were performed to assess reproducibility and agreement. Our results showed that analyses of repeated ROVER measurements revealed MAV mean difference (D)=-0.03±0.53cc (95% CI(-0.22, 0.16)), lower limit of agreement (LLOA)=-1.07cc, and upper limit of agreement (ULOA)=1.01cc; SUV(max) D=0.00±0.00 with LOAs=0.00; cSUV(mean) D=-0.01±0.39 (95% CI(-0.15, 0.13)), LLOA=-0.76, and ULOA=0.75; cMVP(mean) D=-0.52±4.78cc (95% CI(-2.23, 1.23)), LLOA=-9.89cc, and ULOA=8.86cc. Comparisons between ROVER and manual measurements revealed volume D= -0.39±1.37cc (95% CI (-0.89, 0.11)), LLOA=-3.08cc, and ULOA=2.30cc; SUV(max) D=0.00±0.00 with LOAs=0.00. Mean percent increase in lesional SUV(mean) and MVP(mean) following partial volume correction using ROVER was 84.25±36.00% and 84.45±35.94% , respectively. In conclusion, it is feasible to estimate MAV, SUV(max), cSUV(mean), and cMVP(mean) of spinal bone marrow metastases from (18)F-FDG-PET/CT quickly and easily with good reproducibility via ROVER software. Partial volume correction is imperative, as uncorrected SUV(mean) and MVP(mean) are significantly underestimated, even for large lesions. This novel approach has great potential for practical, accurate, and precise combined structural-functional PET quantification of disease before and after therapeutic intervention.

Comment on "Developing DCE-CT to quantify intra-tumor heterogeneity in breast tumors with differing angiogenic phenotype".

In our comment some essential issues concerning determination of arterial input function (AIF), cardiac and respiratory related motion artifacts, contrast agent application and compartmental model fitting done by Cao et al., 2009 are discussed.

Improved multimodality imaging using alginate molding in xenograft tumor models.

PURPOSE: To allow for reproducible rodent positioning using molding in multimodal tomographic imaging (positron emission tomography [PET], magnetic resonance imaging/spectroscopy [MRI/MRS]), minimization of magnetic field inhomogeneity during MRI investigations of peripheral structures, and reproducible positioning for subsequent histological sectioning of the separated tumor. MATERIALS AND METHODS: Chemical shift imaging (CSI) studies were carried out using phantoms and NMRI nu/nu mice bearing subcutaneous tumors. For embedding, three different materials were used: 1) alginate, 2) gelatin, and 3) a mixture of wheat flour and salt. The animals were placed in an animal chamber including position markers visible by MRI and PET. The frozen embedded explanted tumors were sliced and examined autoradiographically as well as histologically. RESULTS: Alginate showed a substantial improvement of magnetic field homogeneity and histological sectioning was superior to the other methods. This embedding led to a significant reduction of the full width at half maximum (FWHM) of the water peak in the peripheral rim of the tumor in comparison to the same peak FWHM without embedding (41 +/- 10 Hz vs. 80 +/- 20 Hz). CONCLUSION: Our research shows that animal positioning in an imaging chamber together with alginate embedding allows high-quality multimodality investigations including coregistration of MRI/MRS, PET, and histological images.

Comparison of [18F]FDG uptake and distribution with hypoxia and proliferation in FaDu human squamous cell carcinoma (hSCC) xenografts after single dose irradiation.

PURPOSE: This study investigated the uptake of [(18)F]2-fluoro-2-deoxy-glucose ([(18)F]FDG) in the human tumour xenograft FaDu at early time points after single dose irradiation with Positron-Emission-Tomography (PET), autoradiography and functional histology. MATERIALS AND METHODS: [(18)F]FDG-PET of FaDu hSCC xenografts on nude mice was performed before 25 Gy or 35 Gy single dose irradiation and one, seven or 11 days post irradiation (p.irr.). Before the second PET, mice were injected with pimonidazole (pimo) and bromodeoxyuridine (BrdU). After the PET tumours were excised, sliced and subjected to autoradiography and functional histology staining (pimo, BrdU, Ki67). [(18)F]FDG tumour uptake was quantified in the PET scans by maximal standard uptake value (SUV(max)) and in the autoradiography after co-registration to the histology slices. RESULTS: No differences in the overall [(18)F]FDG uptake between the two dose groups and time points were found with PET or autoradiography. Comparing autoradiography and histology, the [(18)F]FDG uptake was constant in tumour necrosis over time, while it decreased in vital tumour areas and particularly in hypoxic regions. No differences in the [(18)F]FDG uptake between positive and negative areas of Ki67 and BrdU were found. CONCLUSIONS: The decline of [(18)F]FDG uptake in vital tumour and in pimopositive areas as seen in autoradiography, was not reflected by evaluation of SUV(max) determined by PET. These findings suggest that the SUV(max) does not necessarily reflect changes in tumour biology after irradiation.

Synthesis and application of [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO): a [18F]FDG-based prosthetic group for the chemoselective 18F-labeling of peptides and proteins.

2-[(18)F]Fluoro-2-deoxy-D-glucose ([(18)F]FDG) as the most important PET radiotracer is available in almost every PET center. However, there are only very few examples using [(18)F]FDG as a building block for the synthesis of (18)F-labeled compounds. The present study describes the use of [(18)F]FDG as a building block for the synthesis of (18)F-labeled peptides and proteins. [(18)F]FDG was converted into [(18)F]FDG-maleimidehexyloxime ([(18)F]FDG-MHO), a novel [(18)F]FDG-based prosthetic group for the mild and thiol group-specific (18)F labeling of peptides and proteins. The reaction was performed at 100 degrees C for 15 min in a sealed vial containing [(18)F]FDG and N-(6-aminoxy-hexyl)maleimide in 80% ethanol. [(18)F]FDG-MHO was obtained in 45-69% radiochemical yield (based upon [(18)F]FDG) after HPLC purification in a total synthesis time of 45 min. Chemoselecetive conjugation of [(18)F]FDG-MHO to thiol groups was investigated by the reaction with the tripeptide glutathione (GSH) and the single cysteine containing protein annexin A5 (anxA5). Radiolabeled annexin A5 ([(18)F]FDG-MHO-anxA5) was obtained in 43-58% radiochemical yield (based upon [(18)F]FDG-MHO, n = 6), and [(18)F]FDG-MHO-anxA5 was used for a pilot small animal PET study to assess in vivo biodistribution and kinetics in a HT-29 murine xenograft model.

Localized proton magnetic resonance spectroscopy of lipids in adipose tissue at high spatial resolution in mice in vivo.

We describe a localized proton magnetic resonance spectroscopy ((1)H-MRS) method for in vivo measurement of lipid composition in very small voxels (1.5 mm x 1.5 mm x 1.5 mm) in adipose tissue in mice. The method uses localized point-resolved spectroscopy to collect (1)H spectra from voxels in intra-abdominal white adipose tissue (WAT) and brown adipose tissue (BAT) deposits. Nonlinear least-squares fits of the spectra in the frequency domain allow for accurate calculation of the relative amount of saturated, monounsaturated, and polyunsaturated fatty acids. All spectral data are corrected for spin-spin relaxation. The data show BAT of NMRI mice to be significantly different from BAT of NMRI nu/nu mice in all aspects except for the fraction of monounsaturated fatty acids (FM); for WAT, only the FM is different. BAT and WAT of NMRI mice differ in the amount of saturated and di-unsaturated fatty acids. This method provides a potential tool for studying lipid metabolism in small animal models of disease during the initiation, progression, and manifestation of obesity-related disorders in vivo. Our results clearly demonstrate that localized (1)H-MRS of adipose tissue in vivo is possible at high spatial resolution with voxel sizes down to 3.4 ml.

Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy.

BACKGROUND: Hepatic encephalopathy is considered to be mainly caused by increased ammonia metabolism of the brain. If this hypothesis is true, cerebral glucose utilisation, which is considered to represent brain function, should be closely related to cerebral ammonia metabolism. The aim of the present study was to analyse whether cerebral ammonia and glucose metabolism in cirrhotic patients with early grades of hepatic encephalopathy are as closely related as could be expected from current hypotheses on hepatic encephalopathy. METHODS: (13)N-ammonia and (18)F-fluorodesoxyglucose positron emission tomography, magnetic resonance imaging and magnetic resonance spectroscopy (MRS) were performed in 21 cirrhotic patients with grade 0-1 hepatic encephalopathy. Quantitative values of cerebral ammonia uptake and retention rate and glucose utilisation were derived for several regions of interest and were correlated with the MRS data of the basal ganglia, white matter and frontal cortex. RESULTS: A significant correlation between plasma ammonia levels and cerebral ammonia metabolism, respectively, and MRS alterations could be shown only for white matter. In contrast, MRS alterations in all three regions studied were significantly correlated with the glucose utilisation of several brain regions. Cerebral ammonia and glucose metabolism were not correlated. CONCLUSION: Increase of cerebral ammonia metabolism is an important but not exclusive causal factor for the development of hepatic encephalopathy.

Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo.

Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [(18)F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

Impaired glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy.

Insulin resistance is a frequently observed side effect of highly active antiretroviral therapy (HAART). Currently, very little is known about the mechanisms or specific tissues involved. We aimed to identify possible defects in skeletal muscle glucose uptake and metabolism in HIV patients receiving HAART. Whole-body glucose disposal and oxidation were determined by combination of the euglycemic-hyperinsulinemic clamp technique and indirect calorimetry. Muscle glucose uptake of the thighs was measured simultaneously by dynamic 2[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. Patients receiving HAART had signs of lipodystrophy as confirmed by dual energy x-ray absorptiometry. Whole-body glucose disposal was significantly reduced in these patients compared with untreated patients. Analysis of kinetic constants using a three-compartment model indicated reduced skeletal glucose uptake caused by significantly impaired glucose transport and phosphorylation. Skeletal muscle glucose uptake was reduced by 66% in treated patients and explained 46% and 43% of whole-body glucose disposal in patients on HAART and therapy-naive patients, respectively. Insulin-stimulated whole-body oxidative and nonoxidative glucose disposal was significantly lower in the treated group, as was suppressive insulin action on lipolysis. To our knowledge, this is the first report providing in vivo evidence that, in lipodystrophic HIV patients, impaired glucose transport and phosphorylation cause reduced insulin-mediated glucose uptake.