Biodistribution,radiation dosimetry and scouting of <Superscript>90</Superscript>Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin’s lymphoma using <Superscript>89</Superscript>Zr-ibritumomab tiuxetan and PET

Purpose  

Positron emission tomography (PET) with ⁸⁹Zr-ibritumomab tiuxetan can be used to monitor biodistribution of ⁹⁰Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of ⁹⁰Y-ibritumomab tiuxetan in humans on the basis of ⁸⁹Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of ⁹⁰Y-ibritumomab tiuxetan influences biodistribution of ⁸⁹Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with ⁸⁹Zr-ibritumomab tiuxetan can be used to predict biodistribution of ⁹⁰Y-ibritumomab tiuxetan and the dose-limiting organ during therapy.     

Do androgens control the uptake of <Superscript>18</Superscript>F-FDG, <Superscript>11</Superscript>C-choline and <Superscript>11</Superscript>C-acetate in human prostate cancer cell lines?

Purpose  

The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines—reflecting different stages of the disease—on ¹⁸F-fluorodeoxyglucose (FDG), ¹¹C-choline and ¹¹C-acetate uptake.     

<Superscript>68</Superscript>Ga- and <Superscript>111</Superscript>In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

PURPOSE: alphavbeta3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [(18)F]Galacto-RGD that monitoring of alphavbeta3 expression is feasible. Here, we introduce (68)Ga- and (111)In-labelled derivatives and compare them with [(18)F]Galacto-RGD. METHODS: For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, alphavbeta3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (alphavbeta3 positive) and M21-L (alphavbeta3 negative) cells were used. RESULTS: Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [(68)Ga]DOTA-RGD and only up to 1.4% for [(111)In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in alphavbeta3-positive tumours was 2.9 +/- 0.3%ID/g and in alphavbeta3-negative tumours 0.8 +/- 0.1%ID/g for [(68)Ga]DOTA-RGD ([(111)In]DOTA-RGD: 1.9 +/- 0.3%ID/g and 0.5 +/- 0.2%ID/g; [(18)F]Galacto-RGD: 1.6 +/- 0.2%ID/g and 0.4 +/- 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [(68)Ga]DOTA-RGD, tumour/blood ratios were higher for [(111)In]DOTA-RGD and [(18)F]Galacto-RGD. However, microPET studies demonstrated that visualisation of alphavbeta3-positive tumours using [(68)Ga]DOTA-RGD is possible. CONCLUSIONS: Our data indicate that [(68)Ga]DOTA-RGD allows monitoring of alphavbeta3 expression. Especially, the much easier radiosynthesis compared to [(18)F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [(18)F]Galacto-RGD remains superior for imaging alphavbeta3 expression. Introduction of alternative chelator systems may overcome the disadvantages.     

Comparison of <Superscript>99m</Superscript>Tc-annexin A5 with <Superscript>18</Superscript>F-FDG for the detection of atherosclerosis in ApoE−/− mice

Purpose ^99mTc-annexin A5, a marker of ongoing apoptosis, and ¹⁸F-FDG, a marker of the increased metabolism of inflammatory cells, are supposed to be useful in the detection of metabolically active atheroma. This study reports a comparison of the intralesional distribution of these tracers in relation to lesion development in ApoE−/− mice. Methods Male ApoE−/− mice (n = 12–14/group) were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks, ^99mTc-annexin A5 or ¹⁸F-FDG was injected and the aortas were harvested for autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a semiquantitative parameter for evaluating lesion development). Results Both ^99mTc-annexin A5 and ¹⁸F-FDG showed preferential uptake into atherosclerotic lesions, with higher uptake levels for ¹⁸F-FDG (mean, 56.07 %ID×kg/m²) than for ^99mTc-annexin A5 (mean, 10.38 %ID×kg/m²). The regional uptake levels of each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for ^99mTc-annexin A5; r = 0.56, p < 0.05 for ¹⁸F-FDG). The uptake ratios of advanced lesions (score >0.5) to early lesions (score <0.5) were significantly higher for ^99mTc-annexin A5 than for ¹⁸F-FDG (f = 4.73, p = 0.03). Conclusion Both ^99mTc-annexin A5 and ¹⁸F-FDG accumulate in atherosclerotic lesions and correlate with the severity of each lesion. The higher absolute uptake levels of ¹⁸F-FDG may be advantageous for lesion detection, whereas the preferential uptake of ^99mTc-annexin A5 in advanced lesions may be a useful indicator of late-stage lesions or vulnerable plaque transformation.     

Positron emission tomography imaging of adrenal masses: <Superscript>18</Superscript>F-fluorodeoxyglucose and the 11β-hydroxylase tracer <Superscript>11</Superscript>C-metomidate

Purpose ¹¹C-metomidate (MTO), a marker of 11-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with ¹⁸F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11-hydroxylase in patients with primary aldosteronism.Methods Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushings syndrome, n=4; Conns syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1).Results MTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushings syndrome than in those with Conns syndrome, but the difference did not reach statistical significance. The expression of 11-hydroxylase was not suppressed in the contralateral gland of patients with Conns syndrome, whereas in Cushings syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range.Conclusion MTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11-hydroxylase is lower in Cushings syndrome than in Conns syndrome, and there is no suppression of the contralateral gland in primary aldosteronism; (3) for the purpose of discriminating between benign and malignant lesions, FDG is the tracer of choice.     

Myocardial kinetics of <Superscript>201</Superscript>Thallium, <Superscript>99m</Superscript>Tc-tetrofosmin,and <Superscript>99m</Superscript>Tc-sestamibi in an acute ischemia–reperfusion model using isolated rat heart

Objective ²⁰¹Thallium (TL), ^99mTc-tetrofosmin (TF), and ^99mTc-sestamibi (MIBI) are extensively used as myocardial perfusion agents. The objective of the present study was to evaluate their kinetics under acute ischemia–reperfusion. Methods Isolated rat hearts, perfused by the Langendorff method at a constant flow rate of 10 ml/min, were allotted to normal control, mild ischemia, and severe ischemia groups, in which 20-min tracer wash-in was conducted followed by a 25-min tracer washout. No-flow ischemia (15 min for mild ischemia groups; 30 min for severe ischemia groups) was induced before conducting wash-in and washout in the ischemia groups. Whole-heart radioactivity was determined with an external gamma detector. Myocardial flow rate (K ₁, ml/min) and clearance rate (k ₂, min⁻¹) were calculated. Results K _1TL, K _1TF, and K _1MIBI decreased according to the severity of ischemia (K _1TL 5.32 ± 0.53, 4.76 ± 0.70, and 1.44 ± 0.59; K _1TF 3.80 ± 0.70, 2.73 ± 0.99, and 1.09 ± 0.45; and K _1MIBI 3.45 ± 1.10, 2.15 ± 0.82, and 1.05 ± 0.13, in the normal control, mild, and severe ischemia groups, respectively). K ₁ was significantly higher for TL than for the ^99mTc tracers (P < 0.05), but the ^99mTc tracers had equivalent K ₁ values. k _2TL increased significantly (P < 0.05) in the ischemia groups (k _2TL 0.062 ± 0.013, 0.11 ± 0.045, and 0.12 ± 0.035), but showed no significant difference between the ischemia groups. k _2MIBI and k _2TF were significantly (P < 0.05) lower than k _2TL and increased significantly (P < 0.05) in the severe ischemia group (k _2TF 0.0056 ± 0.0022, 0.0037 ± 0.0015, and 0.024 ± 0.015; and k _2MIBI 0.00072 ± 0.0011, 0.00038 ± 0.00076, and 0.042 ± 0.034). k _2MIBI was significantly (P < 0.05) lower than k _2TF in the normal control and mild ischemia groups. Conclusions Tracer extraction was higher for TL than for the ^99mTc tracers and all tracers decreased according to the severity of ischemia–reperfusion in the three tracer groups. The clearance kinetics of not only MIBI but also TF is possibly useful for the evaluation of the severity of ischemia, and the Langendorff method and a methodological approach by continuous determinations of radioactivity may serve for the quantitative analysis of tracer kinetic profiles.     

<Superscript>18</Superscript>p-FDG PET is superior to<Superscript>67</Superscript>Ga SPECT in the staging of non-Hodgkin’s lymphoma

OBJECTIVE: Our study aims to compare diagnostic accuracy between 18F-FDG PET and 67Ga SPECT in the staging of non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with non-Hodgkin's lymphoma, underwent 18F-FDG PET, 67Ga SPECT and CT for the pretreatment staging of malignant lymphoma between August 1999 and March 2002. 18F-FDG PET imaging was obtained 60 minutes after the intravenous administration of 185 MBq of 18F-FDG. 67Ga SPECT imaging was obtained 2 days after the intravenous administration of 148 MBq of 67Ga. 18F-FDG PET and 67Ga SPECT were performed within one month. Both imagings were performed on the area from the neck to the pelvis. The 18F-FDG PET and 67Ga SPECT findings were compared with the CT findings and the clinical course. RESULTS: Sixty-six nodal lesions were clinically confirmed. Of these, 32 were identified by both 18F-FDG PET and 67Ga SPECT. The remaining 34 lesions were identified only by 18F-FDG PET. The mean (+/- SD) sizes' of the nodes were 34.7 +/- 32.4 mm for 18F-FDG-positive and 67Ga-positive lesions and 15.7 +/- 8.3 mm for 18F-FDG-positive and 67Ga-negative lesions (p < 0.001). Of the 23 extranodal lesions, 12 were identified by both 18F-FDG PET and 67Ga SPECT, whereas 6 lesions were identified by only 18F-FDG PET. Five lesions were not identified by either technique. No 18F-FDG-negative but 67Ga-positive nodal or extranodal lesions were observed. The difference in findings between the two studies is related to the difference in the size but not in the histology or site of the lesions. CONCLUSION: 18F-FDG PET detected significantly more lesions particularly small lesions than 67Ga SPECT. Thus, 18F-FDG PET is considered to be superior to 67Ga SPECT in the staging of non-Hodgkin' s lymphoma.     

<Superscript>18</Superscript>F-labeled mini-PEG spacered RGD dimer (<Superscript>18</Superscript>F-FPRGD2): synthesis and microPET imaging of α<Subscript>v</Subscript>β<Subscript>3</Subscript> integrin expression

Purpose We have previously reported that ¹⁸F-FB-E[c(RGDyK)]₂ (¹⁸F-FRGD2) allows quantitative PET imaging of integrin α_vβ₃ expression. However, the potential clinical translation was hampered by the relatively low radiochemical yield. The goal of this study was to improve the radiolabeling yield, without compromising the tumor targeting efficiency and in vivo kinetics, by incorporating a hydrophilic bifunctional mini-PEG spacer. Methods ¹⁸F-FB-mini-PEG-E[c(RGDyK)]₂ (¹⁸F-FPRGD2) was synthesized by coupling N-succinimidyl-4-¹⁸F-fluorobenzoate (¹⁸F-SFB) with NH₂-mini-PEG-E[c(RGDyK)]₂ (denoted as PRGD2). In vitro receptor binding affinity, metabolic stability, and integrin α_vβ₃ specificity of the new tracer ¹⁸F-FPRGD2 were assessed. The diagnostic value of ¹⁸F-FPRGD2 was evaluated in subcutaneous U87MG glioblastoma xenografted mice and in c-neu transgenic mice by quantitative microPET imaging studies. Results The decay-corrected radiochemical yield based on ¹⁸F-SFB was more than 60% with radiochemical purity of >99%. ¹⁸F-FPRGD2 had high receptor binding affinity, metabolic stability, and integrin α_vβ₃-specific tumor uptake in the U87MG glioma xenograft model comparable to those of ¹⁸F-FRGD2. The kidney uptake was appreciably lower for ¹⁸F-FPRGD2 compared with ¹⁸F-FRGD2 [2.0 ± 0.2%ID/g for ¹⁸F-FPRGD2 vs 3.0 ± 0.2%ID/g for ¹⁸F-FRGD2 at 1 h post injection (p.i.)]. The uptake in all the other organs except the urinary bladder was at background level. ¹⁸F-FPRGD2 also exhibited excellent tumor uptake in c-neu oncomice (3.6 ± 0.1%ID/g at 30 min p.i.). Conclusion Incorporation of a mini-PEG spacer significantly improved the overall radiolabeling yield of ¹⁸F-FPRGD2. ¹⁸F-FPRGD2 also had reduced renal uptake and similar tumor targeting efficacy as compared with ¹⁸F-FRGD2. Further testing and clinical translation of ¹⁸F-FPRGD2 are warranted. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Zhanhong Wu and Zi-Bo Li contributed equally to this work.     

PET imaging of α<Subscript>7</Subscript> nicotinic acetylcholine receptors: a comparative study of [<Superscript>18</Superscript>F]ASEM and [<Superscript>18</Superscript>F]DBT-10 in nonhuman primates,and further evaluation of [<Superscript>18</Superscript>F]ASEM in humans

Purpose

The α₇ nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α₇ nAChRs PET radioligands, [¹⁸F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [¹⁸F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([¹⁸F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [¹⁸F]ASEM in humans.

Methods

PET scans with high specific activity [¹⁸F]ASEM or [¹⁸F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [¹⁸F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [¹⁸F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [¹⁸F]ASEM distribution volume (V _T). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V _T was assessed.

Results

In the rhesus monkey brain [¹⁸F]ASEM and [¹⁸F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [¹⁸F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [¹⁸F]ASEM V _T. [¹⁸F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [¹⁸F]ASEM V _T in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V _T values ranging from 19.6?±?2.5 mL/cm³ in cerebellum to 25.9?±?2.9 mL/cm³ in thalamus. Test-retest variability of V _T was 11.7?±?9.8%.

Conclusions

These results confirm [¹⁸F]ASEM as a suitable radiotracer for the imaging and quantification of α₇ nAChRs in humans.

     

<Superscript>99m</Superscript>Tc-tetrofosmin or <Superscript>99m</Superscript>Tc-sestamibi for double-phase parathyroid scintigraphy?

Several years ago technetium-99m tetrofosmin was reported to localise parathyroid adenomas. The aim of this study was to compare the sensitivity of this radiopharmaceutical with that of (99m)Tc-sestamibi using a double-phase parathyroid scintigraphy protocol. Scans of 12 patients were evaluated visually and lesion to thyroid ratios were calculated. Nine of the patients were subsequently operated on; a total of eight parathyroid adenomas or hyperplastic glands were histologically confirmed in seven of the patients, while in one patient a parathyroid carcinoma was histologically proven. All of these patients had positive (99m)Tc-sestamibi scintigrams, whereas only two (99m)Tc-tetrofosmin scintigrams were positive. With (99m)Tc-sestamibi there was a significant increase in the lesion to thyroid ratio from 10 min to 90 min and 150 min p.i. which was not seen on scintigraphy with (99m)Tc-tetrofosmin. This makes (99m)Tc-tetrofosmin less suitable for double-phase parathyroid scintigraphy.     

Intra-individual comparison of p-[<Superscript>123</Superscript>I]-iodo-L-phenylalanine and L-3-[<Superscript>123</Superscript>I]-iodo-α-methyl-tyrosine for SPECT imaging of gliomas

Objectives Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[¹²³I]-iodo-α-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[¹²³I]-iodo-L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. Methods Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. Results Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95±0.50 versus 1.79±0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA-SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97±0.53 versus 2.21±0.44, p > 0.5) or IPA (1.70±0.23 versus 2.21±0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. Conclusions IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131. This work was supported by a grant from the “Deutsche Krebshilfe” (70-3024-He 1).     

<Superscript>68</Superscript>Ga-labeled multimeric RGD peptides for microPET imaging of integrin α<Subscript>v</Subscript>β<Subscript>3</Subscript> expression

PURPOSE: We and others have reported that (18)F- and (64)Cu-labeled arginine-glycine-aspartate (RGD) peptides allow positron emission tomography (PET) quantification of integrin alpha(v)beta(3) expression in vivo. However, clinical translation of these radiotracers is partially hindered by the necessity of cyclotron facility to produce the PET isotopes. Generator-based PET isotope (68)Ga, with a half-life of 68 min and 89% positron emission, deserves special attention because of its independence of an onsite cyclotron. The goal of this study was to investigate the feasibility of (68)Ga-labeled RGD peptides for tumor imaging. METHODS: Three cyclic RGD peptides, c(RGDyK) (RGD1), E[c(RGDyK)](2) (RGD2), and E{E[c(RGDyK)](2)}(2) (RGD4), were conjugated with macrocyclic chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and labeled with (68)Ga. Integrin affinity and specificity of the peptide conjugates were assessed by cell-based receptor binding assay, and the tumor targeting efficacy of (68)Ga-labeled RGD peptides was evaluated in a subcutaneous U87MG glioblastoma xenograft model. RESULTS: U87MG cell-based receptor binding assay using (125)I-echistatin as radioligand showed that integrin affinity followed the order of NOTA-RGD4 > NOTA-RGD2 > NOTA-RGD1. All three NOTA conjugates allowed nearly quantitative (68)Ga-labeling within 10 min (12-17 MBq/nmol). Quantitative microPET imaging studies showed that (68)Ga-NOTA-RGD4 had the highest tumor uptake but also prominent activity accumulation in the kidneys. (68)Ga-NOTA-RGD2 had higher tumor uptake (e.g., 2.8 +/- 0.1%ID/g at 1 h postinjection) and similar pharmacokinetics (4.4 +/- 0.4 tumor/muscle ratio, 2.0 +/- 0.1 tumor/liver ratio, and 1.1 +/- 0.1 tumor/kidney ratio) compared with (68)Ga-NOTA-RGD1. CONCLUSIONS: The dimeric RGD peptide tracer (68)Ga-NOTA-RGD2 with good tumor uptake and favorable pharmacokinetics warrants further investigation for potential clinical translation to image integrin alpha(v)beta(3).     

Dopamine transporter SPECT using fast kinetic ligands: <Superscript>123</Superscript>I-FP-β-CIT versus <Superscript>99m</Superscript>Tc-TRODAT-1

A comparative study was carried out on two promising presynaptic dopamine transporter single-photon emission tomography (SPECT) radioligands with a fast pharmacokinetic profile, ¹²³I-FP--CIT (FP) and ^99mTc-TRODAT-1 (TR), in order to assess their differential diagnostic power in early parkinsonism and their sensitivity for detection of disease progression. This cross-sectional study was conducted on 96 patients with early-stage parkinsonism referred in a tertiary clinical setting. Mean disease duration was 2.0±1.3 years, and patients had a modified Hoehn and Yahr (H&Y) stage of 1–2 (average 1.2). Forty-seven patients received TR, and 49 received FP. In both groups, ten patients with normal presynaptic function were included as a control population; all other patients were clinically diagnosed as having idiopathic Parkinsons disease. Groups were matched for gender, age, disease duration and modified H&Y stage. Triple-head gamma camera SPECT was analysed using a semiquantitative index of transporter binding (BI). Discriminant analysis with cross-validation resulted in a maximal classification accuracy for FP of 93% (sensitivity 95% and specificity 86%) for the contralateral putamen BI. For TR, the corresponding values were 87% accuracy, 92% sensitivity and 70% specificity. For FP, disease duration was correlated with both the putamen BI (–8.8%/year, =–0.41, P=0.025) and the putamen/caudate ratio (–7.4%/year, =–0.51, P=0.004), but for TR no significant correlation was found (all P values >0.5). In conclusion, both FP and TR show high sensitivity in a clinically relevant setting, but FP has superior accuracy for early differential diagnosis of idiopathic parkinsonism and non-degenerative extrapyramidal disorders, as well as better sensitivity for disease follow-up.     

<Superscript>11</Superscript>C–MET PET/MRI for detection of recurrent glioma

Introduction

Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid ¹¹C–MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma.

Methods

Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid ¹¹C–MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid ¹¹C–MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis.

Results

Hybrid ¹¹C–MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for ¹¹C–MET PET (96.77% and 73.68%), and for hybrid ¹¹C–MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid ¹¹C–MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C–MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing ¹¹C–MET PET/MRI (4.26?±?0,777) to either PET alone (3.44?±?0.705) or MRI alone (3.56?±?0.733).

Conclusion

This feasibility study showed that hybrid PET/MRI might strengthen RANO classification by adding metabolic information to conventional MRI information. Future studies should evaluate the clinical utility of the combined use of ¹¹C–MET PET/MRI in larger patient cohorts.