Availability of both [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTATATE as PRRT agents for neuroendocrine tumors: can we evolve a rational sequential duo-PRRT protocol for large volume resistant tumors?

European Journal of Nuclear Medicine and Molecular Imaging -     

MR arthrography of postoperative knee: for which patients is it useful?

PURPOSE: To assess which postoperative patients benefit most from MR arthrography of the knee. MATERIALS AND METHODS: One hundred consecutive MR arthrograms obtained in patients who had previous knee surgery underwent retrospective review in consensus by three radiologists after prospective reading by one of the three radiologists. Criterion on MR arthrograms for a retear was abnormal tracking of an intraarticular dilute gadolinium-based contrast material and saline mixture into the substance of a meniscus. Patients were separated into three groups: those with more than 25% meniscal resection, those with less than 25% meniscal resection, and those with meniscal repair. All 100 patients had preoperative MR images to review directly in conjunction with the postoperative MR images. Fifty-seven of these 100 patients underwent second-look arthroscopy. RESULTS: Nine patients had MR findings consistent with avascular necrosis. Nineteen patients had marked degenerative arthrosis in the area of previous surgery. Seven patients had chondral defects or injuries. Twenty-nine patients had clear MR evidence of a meniscal retear without any contrast material injected into the joint. In 32 of the 100 patients, intraarticular contrast material was useful in demonstrating a retear. Of these 32 patients, 22 had MR arthrographic evidence of a retear, while 10 had no clear MR arthrographic finding to explain postoperative pain. Four additional patients had no clear MR imaging or MR arthrographic abnormality. All patients with meniscal repair (n = 16) needed MR arthrography to diagnose a residual or recurrent meniscal tear. No patient with less than 25% meniscal resection (n = 23) needed MR arthrography to demonstrate a residual or recurrent meniscal tear. Sixteen of 61 patients with more than 25% meniscal resection needed MR arthrography to demonstrate a residual or recurrent meniscal tear. CONCLUSION: All patients with meniscal repair required MR arthrography. All patients with meniscal resection of more than 25%, who did not have severe degenerative arthrosis, chondral injuries, or avascular necrosis required MR arthrography. Patients with less than 25% meniscal resection did not need MR arthrography.     

Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging?

In these three words--genomics, proteomics and nanotechnologies--is the future of medicine of the third millennium, which will be characterised by more careful attention to disease prevention, diagnosis and treatment. Molecular imaging appears to satisfy this requirement. It is emerging as a new science that brings together molecular biology and in vivo imaging and represents the key for the application of personalized medicine. Micro-PET (positron emission tomography), micro-SPECT (single photon emission computed tomography), micro-CT (computed tomography), micro-MR (magnetic resonance), micro-US (ultrasound) and optical imaging are all molecular imaging techniques, several of which are applied only in preclinical settings on animal models. Others, however, are applied routinely in both clinical and preclinical setting. Research on small animals allows investigation of the genesis and development of diseases, as well as drug efficacy and the development of personalized therapies, through the study of biological processes that precede the expression of common symptoms of a pathology. Advances in molecular imaging were made possible only by collaboration among scientists in the fields of radiology, chemistry, molecular and cell biology, physics, mathematics, pharmacology, gene therapy and oncology. Although until now researchers have traditionally limited their interactions, it is only by increasing these connections that the current gaps in terminology, methods and approaches that inhibit scientific progress can be eliminated.     

Comparison of MR imaging sequences for liver and head and neck interventions: is there a single optimal sequence for all purposes?

RATIONALE AND OBJECTIVES: To compare the appropriate pulse sequences for interventional device guidance during magnetic resonance (MR) imaging at 0.2 T and to evaluate the dependence of sequence selection on the anatomic region of the procedure. MATERIALS AND METHODS: Using a C-arm 0.2 T system, four interventional MR sequences were applied in 23 liver cases and during MR-guided neck interventions in 13 patients. The imaging protocol consisted of: multislice turbo spin echo (TSE) T2w, sequential-slice fast imaging with steady precession (FISP), a time-reversed version of FISP (PSIF), and FISP with balanced gradients in all spatial directions (True-FISP) sequences. Vessel conspicuity was rated and contrast-to-noise ratio (CNR) was calculated for each sequence and a differential receiver operating characteristic was performed. RESULTS: Liver findings were detected in 96% using the TSE sequence. PSIF, FISP, and True-FISP imaging showed lesions in 91%, 61%, and 65%, respectively. The TSE sequence offered the best CNR, followed by PSIF imaging. Differential receiver operating characteristic analysis also rated TSE and PSIF to be the superior sequences. Lesions in the head and neck were detected in all cases by TSE and FISP, in 92% using True-FISP, and in 84% using PSIF. True-FISP offered the best CNR, followed by TSE imaging. Vessels appeared bright on FISP and True-FISP imaging and dark on the other sequences. CONCLUSION: In interventional MR imaging, no single sequence fits all purposes. Image guidance for interventional MR during liver procedures is best achieved by PSIF or TSE, whereas biopsies in the head and neck are best performed using FISP or True-FISP sequences.     

Comparison of high resolution CT findings of sarcoidosis, lymphoma, and lymphangitic carcinoma: is there any difference of involved interstitium?

PURPOSE: The purpose of this study was to determine distinguishing features of three diseases that are distributed along the lymphatics. METHOD: CT scans of 40 patients with lymphangitic carcinomatosis, 41 with sarcoidosis, and 44 with malignant lymphoma were retrospectively reviewed. We evaluated the degree of involvement of the interlobular septa, bronchovascular structures, subpleural interstitium, and other CT findings. RESULTS: The number of thickened interlobular septa and the extent of involvement of the subpleural interstitium in lymphangitic carcinomatosis were higher than those in sarcoidosis and malignant lymphoma (p<0.0001). Nodules of >1 cm in diameter were more often seen in malignant lymphoma (41.0%) than in the other two diseases (p < 0.001). Bilateral distribution was more common in sarcoidosis (100%) than in the others (p<0.001). CONCLUSION: The major difference among lymphangitic carcinomatosis, sarcoidosis, and malignant lymphoma is the greater involvement of the interlobular septa and subpleural interstitium in lymphangitic carcinomatosis than in either sarcoidosis or malignant lymphoma.     

PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

AIM: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [11C]R121920 and [11C]DMP696 in the nonhuman primate for application in positron emission tomography (PET) studies of CRF1. METHODS: PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET. RESULTS: Both [11C]R121920 and [11C]DMP696 distributed rapidly and uniformly throughout the brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [(125)I]Tyr(0)-sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (Bmax) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded Bmax of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K(D)) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore, Bmax and K(D) were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. CONCLUSION: Neither [11C]R121920 nor [11C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum.     

Comparison of 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours

Purpose

Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT) positron emission tomography (PET) and [¹⁸F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery.

Methods

A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images.

Results

Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n?=?31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV_max 1.1–6.5; mean FDG SUV_max 7.9, range 3.3–17.8; p?Conclusion For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.     

[18F]3′-deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors

Abstract The aim of this study was to evaluate the feasibility of using [¹⁸F] 3-deoxy-3-fluorothymidine (FLT) positron emission tomography (PET) for the diagnosis and grading of brain tumors.Methods The patient population comprised 26 patients (15 males, 11 females) with brain tumors (n=18) or nontumorous lesions (n=8). 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) and FLT PET images were obtained using a dedicated PET scanner 1 h after the injection of 370 MBq of FDG or FLT. Uptake of FDG and FLT by the lesions was visually and semiquantitatively assessed in comparison with normal brain tissue.Results Of 26 brain lesions, four showed increased FDG uptake compared with normal gray matter (grade 5). These four lesions showed intensely increased FLT uptake and were all high-grade tumors. Twenty-two lesions with similar (grade 4) or decreased (grades 1–3) FDG uptake compared with normal gray matter showed variable pathology. Among the 18 brain tumors, FLT PET showed increased uptake in all 12 high-grade tumors but FDG uptake was variable. In 22 brain lesions with similar or decreased uptake compared with normal gray matter on FDG PET, the sensitivity and specificity of FLT PET for the diagnosis of brain tumor were 79% (11/14) and 63% (5/8), respectively. The uptake ratios of 14 brain tumors on FLT PET were significantly higher than the lesion to gray matter ratios (p=0.012) and lesion to white matter ratios (p=0.036) of FDG uptake and differed significantly between high (5.1±2.6) and low (2.1±1.1) grade tumors (p=0.029). In nine gliomas, FLT uptake was significantly correlated with the Ki-67 proliferation index (rho=0.817, p=0.007).Conclusion These findings indicate that FLT PET is useful for evaluating tumor grade and cellular proliferation in brain tumors. It displayed high sensitivity and good contrast in evaluating brain lesions that showed similar or decreased uptake compared with normal gray matter on FDG PET. FLT PET, however, did not appear to be sufficiently useful for differentiating tumors from nontumorous lesions.     

Comparison of [123I]ß-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates

Single-photon emission tomographic (SPET) imaging with the radiotracer [¹²³I]2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity,-CIT also binds with high affinity to serotonin (5-HT) transporters. 2-Carboisopropoxy-3-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [¹²³I]-CIT and [¹²³I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [¹²³I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma¹²³I activity) of lipophilic radiolabeled metabolites at 420 min. [¹²³I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [¹²³I]-CIT and [¹²³I]IPCIT were 52%±7% and 14%±6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [¹²³I]-CIT (1.7±0.5) was higher than that of [¹²³I]IPCIT (0.4±0.2). Consistent with its greater lipophilicity, [¹²³I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [¹²³I]IPCIT was about twice that of [¹²³I]-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [¹²³I]-CIT compared to [¹²³I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different. In conclusion, [¹²³I]IPCIT demonstrated in vivo a higher DA transporter selectivity and higher level of nonspecific uptake.     

Diagnostic performance of qualitative and radiomics approach to parotid gland tumors: which is the added benefit of texture analysis?

Objective:To investigate whether MRI-based texture analysis improves diagnostic performance for the diagnosis of parotid gland tumors compared to conventional radiological approach.Methods:Patients with parotid gland tumors who underwent salivary glands MRI between 2008 and 2019 were retrospectively selected. MRI analysis included a qualitative assessment by two radiologists (one of which subspecialized on head and neck imaging), and texture analysis on various sequences. Diagnostic performances including sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of qualitative features, radiologists’ diagnosis, and radiomic models were evaluated.Results:Final study cohort included 57 patients with 74 tumors (27 pleomorphic adenomas, 40 Warthin tumors, 8 malignant tumors). Sensitivity, specificity, and AUROC for the diagnosis of malignancy were 75%, 97% and 0.860 for non-subspecialized radiologist, 100%, 94% and 0.970 for subspecialized radiologist and 57.2%, 93.4%, and 0.927 using a MRI radiomics model obtained combining texture analysis on various MRI sequences. Sensitivity, specificity, and AUROC for the differential diagnosis between pleomorphic adenoma and Warthin tumors were 81.5%, 70%, and 0.757 for non-subspecialized radiologist, 81.5%, 95% and 0.882 for subspecialized radiologist and 70.8%, 82.5%, and 0.808 using a MRI radiomics model based on texture analysis of T₂ weighted sequence. A combined radiomics model obtained with all MRI sequences yielded a sensitivity of 91.5% for the diagnosis of pleomorphic adenoma.Conclusion:MRI qualitative radiologist assessment outperforms radiomic analysis for the diagnosis of malignancy. MRI predictive radiomics models improves the diagnostic performance of non-subspecialized radiologist for the differential diagnosis between pleomorphic adenoma and Warthin tumor, achieving similar performance to the subspecialized radiologist.Advances in knowledge:Radiologists outperform radiomic analysis for the diagnosis of malignant parotid gland tumors, with some MRI qualitative features such as ill-defined margins, perineural spread, invasion of adjacent structures and enlarged lymph nodes being highly specific for malignancy. A radiomic model based on texture analysis of T₂ weighted images yields higher specificity for the diagnosis of pleomorphic adenoma compared to a radiologist non-subspecialized in head and neck radiology, thus minimizing false-positive pleomorphic adenoma diagnosis rate and reducing unnecessary surgical complications.     

After Kosovo, Afghanistan and Iraq: what is the future for the UN?

There have been enormous changes in the world order over the last 15 years, which have seen the United States, closely supported by the United Kingdom, become more unilateral in its actions, and in doing so damaging the United Nations. Attempts to create an ethical dimension in foreign policy have failed. The brief consensus after 9/11 has been lost in the war against terror, whilst other more appropriate measures to diminish the risks of terrorism, such as creating greater equity in trade and meeting the UN millennium goals, have been left to one side. Iraq and the ongoing failure to resolve the Palestinian issues have left the world a less safe place. The need for the UN to establish itself as a dominant force for global justice is paramount. To do so there must be reform, particularly of the Security Council.     

A comparative study of evaluation of radiographs, CT and 3D reformatted CT in facial trauma: what is the role of 3D?

A panel of 17 trainee maxillofacial surgeons viewed 23 cases of facial trauma, demonstrated on radiographs, axial CT images and three-dimensional (3D) reformatted CT images in a standardized viewing format under standard conditions. Their diagnostic interpretation, extraction of information relevant to surgical management and subjective evaluation of each modality were recorded by standard questionnaire and compared with a gold standard evaluation by a consultant radiologist and surgeon reading based on results of clinical management. There were clear and measurable differences in the viewers' evaluations of radiographs, CT and 3D reformatted images. Overall, surgeons showed more accurate diagnostic reading of radiographs and 3D reformatted images. This was in contrast to their subjective assessment of the clinical value of each modality, which showed a strong preference for 3D over all other techniques and for CT over radiographs. However the perceived benefit of axial CT images over radiographs was not reproduced on objective testing in this group; surgeons appear to perform less well in interpreting CT images than their subjective response to the modality would suggest. This work has supported the view that surgeons value 3D imaging as a front-line tool in the evaluation and management of selected cases of acute facial trauma. We have demonstrated that the perceived benefits of 3D reformatted CT to surgeons appear real.     

Synthesis and evaluation of [11C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β)

IntroductionThe dysfunction of glycogen synthase kinase-3β (GSK-3β) has been implicated in a number of diseases, including Alzheimer’s disease. The ability to non-invasively quantify GSK-3β activity in vivo is therefore of critical importance, and this work is focused upon development of inhibitors of GSK-3β radiolabeled with carbon-11 to examine quantification of the enzyme using positron emission tomography (PET) imaging.Methods¹¹C PyrATP-1 was prepared from the corresponding desmethyl-piperazine precursor in an automated synthesis module. In vivo rodent and primate imaging studies were conducted on a Concorde MicroPET P4 scanner to evaluate imaging properties and in vitro autoradiography studies with rat brain samples were carried out to examine specific binding.Results2035 ± 518 MBq (55 ± 14 mCi) of [¹¹C]PyrATP-1 was obtained (1%–2% non-corrected radiochemical yield at end-of-synthesis based upon [¹¹C]CO₂) with high chemical (> 95%) and radiochemical (> 99%) purities, and good specific activities (143 ± 52 GBq/μmol (3874 ± 1424 Ci/mmol)), n = 5. In vivo microPET imaging studies revealed poor brain uptake in rodents and non-human primates. Pretreatment of rodents with cyclosporin A resulted in moderately increased brain uptake suggesting Pgp transporter involvement. Autoradiography demonstrated high levels of specific binding in areas of the rodent brain known to be rich in GSK-3β.Conclusion¹¹C PyrATP-1 is readily synthesized using standard carbon-11 radiochemistry. However the poor brain uptake in rodents and non-human primates indicates that the radiotracer is not suitable for the purposes of quantifying GSK-3β in neurological and psychiatric disorders.