Gamma camera imaging characteristics of 166Ho and 99mTc used in Selective Internal Radiation Therapy.

BACKGROUND: The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms. METHODS: Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed. RESULTS: The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes. CONCLUSIONS: Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT.

Aortic Vascular Graft and Endograft Infection-Patient Outcome Cannot Be Determined Based on Pre-Operative Characteristics.

Vascular graft/endograft infection (VGEI) is a serious complication after aortic surgery. This study investigates VGEI and patient characteristics, PET/CT quantification before surgical or conservative management of VGEI and post-intervention outcomes in order to identify patients who might benefit from such a procedure. PET standard uptake values (SUV) were quantitatively assessed and compared to a non-VGEI cohort. The primary endpoints were in-hospital mortality and aortic reintervention-free survival at six months. Ninety-three patients (75% male, 65 ± 10 years, 82% operated) were included. The initial operation was mainly for aneurysm (67.7%: 31% EVAR, 12% TEVAR, 57% open aortic repair). Thirty-two patients presented with fistulae. PET SUVTLR (target-to-liver ratio) showed 94% sensitivity and 89% specificity. Replacement included silver-coated Dacron (21.3%), pericardium (61.3%) and femoral vein (17.3%), yet the material did not influence the overall survival (p = 0.745). In-hospital mortality did not differ between operative and conservative treatment (19.7% vs. 17.6%, p = 0.84). At six months, 50% of the operated cohort survived without aortic reintervention. Short- and midterm morbidity and mortality remained high after aortic graft removal. Neither preoperative characteristics nor the material used for reconstruction influenced the overall survival, and, with limitations, both the in-hospital and midterm survival were similar between the surgically and conservatively managed patients.

Alpha-Emitting Radionuclides: Current Status and Future Perspectives.

The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress. A particular area of research is the use of alpha-emitting radionuclides, which have unique physical properties associated with outstanding advantages, e.g., for single tumor cell targeting. Here, recent results and open questions regarding the production of alpha-emitting isotopes as well as their chemical combination with carrier molecules and clinical experience from compassionate use reports and clinical trials are discussed.

Influence of the Molar Activity of 203/212Pb-PSC-PEG2-TOC on Somatostatin Receptor Type 2-Binding and Cell Uptake.

(1) Background: In neuroendocrine tumors (NETs), somatostatin receptor subtype 2 is highly expressed, which can be targeted by a radioactive ligand such as [177Lu]Lu-1,4,7,10-tetraazacyclododecane-N,N',N″,N‴,-tetraacetic acid-[Tyr3,Thr8]-octreotide (177Lu-DOTA-TOC) and, more recently, by a lead specific chelator (PSC) containing 203/212Pb-PSC-PEG2-TOC (PSC-TOC). The molar activity (AM) can play a crucial role in tumor uptake, especially in receptor-mediated uptake, such as in NETs. Therefore, an investigation of the influence of different molar activities of 203/212Pb-PSC-TOC on cell uptake was investigated. (2) Methods: Optimized radiolabeling of 203/212Pb-PSC-TOC was performed with 50 µg of precursor in a NaAc/AcOH buffer at pH 5.3-5.5 within 15-45 min at 95° C. Cell uptake was studied in AR42 J, HEK293 sst2, and ZR75-1 cells. (3) Results: 203/212Pb-PSC-TOC was radiolabeled with high radiochemical purity >95% and high radiochemical yield >95%, with AM ranging from 0.2 to 61.6 MBq/nmol. The cell uptake of 203Pb-PSC-TOC (AM = 38 MBq/nmol) was highest in AR42 J (17.9%), moderate in HEK293 sstr (9.1%) and lowest in ZR75-1 (0.6%). Cell uptake increased with the level of AM. (4) Conclusions: A moderate AM of 15-40 MBq/nmol showed the highest cell uptake. No uptake limitation was found in the first 24-48 h. Further escalation experiments with even higher AM should be performed in the future. It was shown that AM plays an important role because of its direct dependence on the cellular uptake levels, possibly due to less receptor saturation with non-radioactive ligands at higher AM.

[Late neurological consequences of a SARS-CoV-2 infection]. / Neurologische Spätfolgen einer SARS-CoV-2-Infektion.

BACKGROUND: Persistent neurological late symptoms of SARS-CoV-2 infection are common and require regular follow-up treatment. In order to establish uniform therapy concepts, it is necessary to evaluate individual therapeutic approaches for long COVID and post-COVID-19 syndrome. ANAMNESE: A 62-year-old patient was admitted to our rehab clinic for follow-up treatment after severe SARS-CoV-2 infection with neurological symptoms. The initially extensive laboratory and imaging investigation did not reveal any organic cause for the sometimes apoplectiform, complex clinical picture, so that the patient was transferred directly to our rehabilitation clinic in the event of everyday restrictions and rollator dependency. EXAMINATION AND FINDINGS: Clinically, there was a reduced general condition and the mood was depressed. Neurological symptoms were gait ataxia, hand tremor, amnesic aphasia and reduced ability to concentrate. PET / CT showed no evidence of tumor or inflammation. THERAPY AND PROGRESS: A multimodal therapy program consisting of physiotherapy and occupational therapy as well as psychological support was carried out. In addition, off-label therapy with oral glucocorticoids and colchicine was initiated. In the course of the disease, there was a clear reduction in all symptoms with little residual hand tremor. CONCLUSIONS: Whole body and brain FDG PET can be helpful in long COVID and post-COVID-19 syndrome patients with neurological symptoms of unknown origin. These patients benefit from systematic rehabilitation. Glucocorticoids and colchicine appear to accelerate symptom reduction. The rehabilitative therapy should be continued on an outpatient basis.

Altered expression of costimulatory molecules in dementias.

Although the expression of co-stimulatory molecules plays an important role in the immune system, only little is known about their regulation in dementias. Therefore, we determined the expression of CD28, ICOS (CD278) and CTLA-4 (CD152) by CD4 + and CD8 + T cells in the peripheral blood of patients with mild cognitive impairment (MCI; N = 19), Alzheimer's disease (AD; N = 51), vascular dementia (VD; N = 21) and frontotemporal dementia (FTD; N = 6) at the point in time of diagnosis compared to 19 non-demented elderly persons. The expression of CD28 and ICOS by CD4 + and CD8 + T cells was not changed in AD, FTD or VD patients. The expression of the negative regulator CTLA-4 was increased by CD4 + T cells from AD and FTD patients and by CD8 + T cells from VD patients. The classification of the AD patients according to the severity of the disorder showed stage-dependent alterations of CD28, ICOS and CTLA-4 expression. In AD patients, the correlation analysis showed an association between the decline in CD28 + T cells and the increase in CTLA-4 + T cells with cognitive decline, measured by the mini-mental state examination (MMSE), tau proteins and Amyloid-ß, important AD biomarkers in cerebrospinal fluid (CSF). In FTD patients, a positive association between Q Albumin, a marker for blood-CSF-barrier function, and CD28 and a negative correlation between Q Albumin and ICOS expression were determined. Our data suggest a dysregulated balance between the expression of negative and positive co-stimulatory molecules by T cells in AD patients, which might contribute to chronic inflammation observed in dementia.

11C-Methionine Uptake in the Lactating Human Breast.

ABSTRACT: A 33-year-old nursing mother who underwent resection of a glioblastoma of the right hemisphere was referred for a 11C-methionine PET/MR scan to exclude cancer recurrence. In whole-body PET imaging, a slight radiotracer uptake could be observed in the mammary glands, reflecting lactation status. In this case report, we initially describe 11C-methionine uptake in the human breast and discuss any consequences arising from this special situation.

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis.

BACKGROUND: The analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. METHODS: A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [68Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. RESULTS: Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). CONCLUSION: In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

Dementia-associated changes of immune cell composition within the cerebrospinal fluid.

Inflammation and alterations in essential protein structures in the brain might also change the cellular distribution in the cerebrospinal fluid (CSF). Using flow cytometry, we analyzed cell populations of the innate and adaptive immune system associated with the most frequent forms of dementias. We included patients with mild cognitive impairment (MCI; N â€‹= â€‹33), Alzheimer's disease (AD; N â€‹= â€‹90), vascular dementia (VD; N â€‹= â€‹35) and frontotemporal dementia (FTD; N â€‹= â€‹17) at the time of diagnosis, before onset of treatment and 11 elderly non-demented individuals. Dependent on the form of dementia, an increased frequency of CD14+ monocytes, NK cells and NKT cells was measured. Within the T cell population, a dementia-associated shift from central memory towards (late-stage) effector cells was detected. T cells and NKT cells were correlated with MMSE, NK and NKT cells were correlated with ptau, CD14+ monocytes and NK cells were correlated with Amyloid-ß 1-40. Our data suggest that each investigated immune cell type is involved in dementia-associated alterations within the CSF, possibly having distinct functions in their pathogenesis.

Spleno-aortic radiodensity ratio - A distinctive imaging feature to predict short-term outcome in critical care unit.

INTRODUCTION: To investigate the value of contrast-enhanced CT findings - splenic and aortic radiodensities and their ratios (spleno-aortic ratio) - in predicting the prognosis of critical care unit patients (CCU). METHODS: One hundred thirteen continuous CCU patients with an acute deterioration (Group A: 37 women, age: 67.2 ± 14.0 years) were included in the retrospective study. Radiodensities of the spleen and aorta were evaluated by two radiologists separately. The spleno-aortic ratio was calculated. Matthews correlation coefficient (MCC) was used in conjunction with receiver operating characteristic analysis (ROC) to assess if and which parameter was most suitable for short-term mortality prediction. The intra-class correlation coefficient assessed consensus across readers. To validate the results for the best predictor, a second cohort was evaluated (Group B: 354 CT scans). RESULTS: The portal venous spleno-aortic ratio was best suited to predict 72-hour mortality (AUC = 0.91). A threshold ratio ≤0.53 predicted short-term mortality with a high sensitivity (80.95%) and specificity (96.74%, MCC = 0.79). The post-test probability was 85%, assuming a pre-test probability of 18.6% (72-hour mortality rate). ICCs of HU measurements in the aorta, spleen, and its ratios showed high interrater agreement (ICC: 0.92-0.99). In a control cohort, a threshold ratio ≤0.53 predicted CCU patients outcome satisfactorily (SENS = 83.93%, SPEC = 97.65%, PPV = 87.00%, NPV = 97.00%). CONCLUSIONS: The portal venous spleno-aortic ratio serves as a distinctive imaging feature to predict short-term mortality. For CCU patients with a cut-off portal venous spleno-aortic ratio ≤0.53, the risk of dying within three days after CT scan is approximately twenty times higher.

Diagnostic performance of 18F-fluorodeoxyglucose-PET/MRI versus MRI alone in the diagnosis of pelvic recurrence of rectal cancer.

PURPOSE: To compare the diagnostic performance of 18F-fluorodeoxyglucose-PET/MRI and MRI in the diagnosis of pelvic recurrence of rectal cancer. METHODS: All PET/MRIs of patients in the follow-up of rectal cancer performed between 2011 and 2018 at our institution were retrospectively reviewed. Recurrence was confirmed/excluded either by histopathology or imaging follow-up (> 4 months). Four groups of readers (groups 1/2: one radiologist each, groups 3/4: one radiologist/one nuclear medicine physician) independently interpreted MRI and PET/MRI. The likelihood of recurrence was scored on a 5-point-scale. Inter-reader agreement, sensitivity, specificity, PPV/NPV and accuracy were assessed. ROC curve analyses were performed. RESULTS: Fourty-one PET/MRIs of 40 patients (mean 61 years ± 10.9; 11 women, 29 men) were included. Sensitivity of PET/MRI in detecting recurrence was 94%, specificity 88%, PPV/NPV 97% and 78%, accuracy 93%. Sensitivity of MRI was 88%, specificity 75%, PPV/NPV 94% and 60%, accuracy 85%. ROC curve analyses showed an AUC of 0.97 for PET/MRI and 0.92 for MRI, but the difference was not statistically significant (p = 0.116). On MRI more cases were scored as equivocal (12% versus 5%). Inter-reader agreement was substantial for PET/MRI and MRI (0.723 and 0.656, respectively). CONCLUSION: 18F-FDG-PET/MRI and MRI are accurate in the diagnosis of locally recurrent rectal cancer. Sensitivity, specificity, PPV, NPV and accuracy are comparable for both modalities, but PET/MRI increases readers' confidence levels and reduces the number of equivocal cases.

Comparison of 6-[18F]FDOPA PET with Nigrosome 1 detection in patients with parkinsonism.

BACKGROUND: The functional 6-[18F]FDOPA positron emission tomography (PET) can be a helpful tool in differentiating parkinsonism with dopaminergic deficiency from clinically similar differential diagnoses. Furthermore, in T2*/susceptibility-weighted imaging (SWI) magnetic resonance imaging (MRI) sequences the structural integrity of the Nigrosome 1 (N1) can be assessed by checking the presence of the swallow tail sign (STS). We therefore retrospectively compared the performance of the 6-[18F]FDOPA PET with the N1 detection in patients suspected with parkinsonian diseases. Forty-three consecutive patients (m: 23, f: 20, mean age: 63 ± 12 years) were included in the study. They underwent clinically indicated 6-[18F]FDOPA PET/MRI scans as part of their neurological evaluation of uncertain parkinsonian syndromes. Visual and semi-quantitative PET imaging results were statistically compared with visual N1 assessment on 3 T SWI. As the gold standard, we defined the clinical diagnosis at the last follow-up, which included idiopathic Parkinson syndrome (IPS; n = 18), atypical parkinsonian syndromes (APS; n = 9) and other neurological diseases without dopaminergic deficit (n = 16). RESULTS: Thirty-five of 43 patients (81%, Kappa 0.611) had corresponding results in 6-[18F]FDOPA PET and SWI. Seven of the remaining 8 patients were correctly diagnosed by 6-[18F]FDOPA PET alone. Sensitivity, specificity and accuracy for 6-[18F]FDOPA and N1 imaging were 93%, 94%, 93% and 82%, 75%, 79%, respectively. CONCLUSIONS: 6-[18F]FDOPA PET and Nigrosome 1 evaluation had an overall good intermodality agreement. Diagnostic agreement was very good in cases of clinically suspected idiopathic Parkinson syndrome and fair in atypical parkinsonian syndromes, but poor in patients with non-parkinsonian disorders. 6-[18F]FDOPA PET showed higher sensitivity, specificity and accuracy in discriminating parkinsonian syndromes from non-parkinsonian disorders than the N1 evaluation. In summary, the additional benefit of N1 assessment in patients with APS or parkinsonism without dopaminergic deficit needs to be proven by prospective studies.

Hepatic Vascular Malformation Mimics PSMA-Positive Prostate Cancer Metastasis.

An 80-year-old man developed high-risk prostate cancer after 7 years of active surveillance. For staging and treatment planning, a Ga-PSMA PET/MRI was performed. Besides the PSMA-positive primary tumor and a solitary bone metastasis in the fifth thoracic vertebral body, an intensive intrahepatic PSMA expression (SUVmax, 16.3) was suspicious for a liver metastasis. The results of a previously performed contrast-enhanced CT, a consecutively performed contrast-enhanced ultrasound, and a follow-up PSMA PET/CT after 4 months with a stable lesion during androgen deprivation lead to the diagnosis of a vascular malformation metabolically mimicking a hepatic metastasis of the prostate tumor.

68Ga-RM2 PET in PSMA- positive and -negative prostate cancer patients.

AIM: 68Ga-PSMA-11 is the gold standard for molecular imaging of prostate cancer. However, recurrent tumor manifestations or metastases cannot be detected in every case. Therefore, we investigated if there is an additive value of the gastrin-releasing peptide receptor (GRP-R) ligand 68Ga-RM2 compared to the well-established 68Ga-PSMA-11 in patients with (Group 1) and without (Group 2) pathologic PSMA-expression in different tumor stages. PATIENTS AND METHODS: Sixteen men (median age: 74 years, range 50-80 years) with prostate cancer in different stages who had a recent negative (n = 8) or pathologic (n = 8) PSMA PET underwent a subsequent 68Ga-RM2 PET. Both examinations were analyzed qualitatively and quantitatively and compared in terms of pathologic and physiologic tracer distribution. RESULTS: None of the PSMA-negative patients showed any pathological RM2-accumulation. Pathologic PSMA-uptake was observed in 8 patients of whom 5 had pathologic RM2-uptake. The number of patients with a local recurrence was equal in both scans (n = 3). Bone metastases and lymph node metastases were detected in less patients in RM2 PET compared to PSMA PET (n = 4 vs. 7 and n = 2 vs. 5, respectively). In one patient, PSMA-positive liver metastases were not detected in RM2. RM2 PET revealed two additional lesions indicative for bone metastases in two patients with multiple PSMA-positive bone metastases, which had no therapeutic consequence. CONCLUSION: At least in our small and heterogeneous patient population, 68Ga-RM2 showed no clinically relevant, additional benefit compared to 68Ga-PSMA-11 PET.

Diagnosis of Huntington's disease via sequential 18F-DOPA and 18F-FDG PET/MRI.

Cases of rare movement disorders like Huntington's disease (HD) are not easy to diagnose, especially when occurring sporadically, without documented family history. In HD patients, MRI scans commonly feature atrophy of the striatum and reduced volume of white matter. But if morphological findings remain unspecific, functional PET imaging could provide valuable information to further clarify diagnosis. We present a case report of a 56-year-old woman suffering from mild hypokinetic-rigid syndrome and depression, suspicious of Parkinson's disease, who was referred to 18F-DOPA and 18F-FDG PET/MRI scans at our department.

Dual-time-point 64 Cu-PSMA-617-PET/CT in patients suffering from prostate cancer.

Regardless of its high positron energy, 68 Ga-labeled PSMA ligands have become standard of care in metabolic prostate cancer imaging. 64 Cu, a radionuclide with a much longer half-life (12.7 h), is available for PSMA labeling allowing imaging much later than 68 Ga. In this study, the diagnostic performance of 64 Cu-labeled PSMA was compared between early and late scans. Sixteen men (median age: 70 y) with prostate cancer in different stages underwent 64 Cu-PSMA-617-PET/CT 2 and 22 hours post tracer injection. Pathologic and physiologic uptakes were analyzed for both points of time. Pathologic tracer accumulations occurred in 12 patients. Five patients presented with pathologic uptake in 17 different lymph nodes, two patients showed pathologic bone uptake in nine lesions, and seven patients had pathologic PSMA uptake in eight prostatic lesions. Physiologic uptake of the renal parenchyma, urine bladder, and salivary glands decreased over time, while the physiologic uptake of liver and bowel increased. In the present study, 64 Cu-PSMA-617-PET demonstrated to be feasible for imaging prostate cancer for both the primary tumor site and metastases. Later imaging showed no additional, clinically relevant benefit compared with the early scans. At least the investigated time points we chose did not vindicate the additional expenditure.

Brain Metastases of a Neuroendocrine Tumor Visualized by 68Ga-DOTATATE PET/CT.

A 65-year-old woman with a long history of metastasized, highly differentiated (G1) neuroendocrine tumor of pancreatic origin presented for follow-up Ga-DOTATATE PET/CT after 7 peptide receptor radiotherapies. In the previous scan, she already had discrete intracranial tracer accumulations, which were massively progressive in the recent Ga-DOTATATE PET/CT 8 months later. This case illustrates that cerebral metastases in neuroendocrine tumors may occur many years after initial diagnosis, and their somatostatin receptor expression may rise within a few months to a level that reasonably justifies further peptide receptor radiotherapy.

Unexpected Bone Metastases in 99mTc-Pertechnetate Scan of Recurrent Goiter.

A 68-year-old woman who underwent a thyroidectomy for bilateral goiter 20 years ago was referred to our department. The examination revealed a newly occurred thyroid nodule in the right central lobe. Unexpectedly the Tc-pertechnetate scan revealed several extrathyroidal foci right-sided supraclavicular, beside a cold thyroid nodule in the right lower lobe. Consecutive surgery and histology confirmed the suspected diagnosis of follicular thyroid cancer with multiple bone metastases. Whole-body scintigraphy performed after the following radioiodine therapy indicated disseminated osseous metastases.

Prostate-Specific Membrane Antigen Expression in Distal Radius Fracture.

A 79-year old man with prostate cancer under active surveillance for 5 years was referred for a PSMA-PET/MRI for re-evaluation because of a rising prostate-specific antigen value. PET/MRI revealed a ribbonlike tracer accumulation in a healing fracture of the distal radius. This case illustrates that PSMA expression may occur in healing bone fractures in the distal radius. It can be assumed that benign causes of tracer accumulations in the upper extremities are missed in PET/CT due to elevated position of the arms during image acquisition.