Desiree Weiberg

Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque using 68Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden

The CXC-motif chemokine receptor 4 (CXCR4) represents a promising target for molecular imaging of different CXCR4-positive cell types in cardiovascular diseases such as atherosclerosis and arterial wall injury. The aim of this study was to assess the prevalence, pattern, and clinical correlates of arterial wall accumulation of 68Ga-pentixafor, a specific CXCR4 ligand for PET. Methods: The data for 51 patients who underwent 68Ga-pentixafor PET/CT for noncardiovascular indications were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed qualitatively and semiquantitatively by blood-pool–corrected target-to-background ratios. Tracer uptake was compared with calcified plaque burden and cardiovascular risk factors. Results: Focal arterial uptake of 68Ga-pentixafor was seen at 1,411 sites in 51 (100%) of patients. 68Ga-pentixafor uptake was significantly associated with calcified plaque burden (P < 0.0001) and cardiovascular risk factors including age (P < 0.0001), arterial hypertension (P < 0.0001), hypercholesterolemia (P = 0.0005), history of smoking (P = 0.01), and prior cardiovascular events (P = 0.0004). Both the prevalence (P < 0.0001) and the signal intensity (P = 0.009) of 68Ga-pentixafor uptake increased as the number of risk factors increased. Conclusion: 68Ga-pentixafor PET/CT is suitable for noninvasive, highly specific PET imaging of CXCR4 expression in the atherosclerotic arterial wall. Arterial wall 68Ga-pentixafor uptake is significantly associated with surrogate markers of atherosclerosis and is linked to the presence of cardiovascular risk factors. 68Ga-pentixafor signal is higher in patients with a high-risk profile and may hold promise for identification of vulnerable plaque.

Multitracer Molecular Imaging of Paget Disease Targeting Bone Remodeling, Fatty Acid Metabolism, and PSMA Expression on PET/CT.

Paget disease is a chronic disorder resulting in enlarged and misshapen bones, and is caused by disorganized bone remodeling. We present the case of an 85-year-old man with prostatic adenocarcinoma and known Paget disease of the right iliac bone who underwent Ga-prostate-specific membrane antigen ligand, C-acetate, and F-fluoride PET/CT for restaging of cancer. On all PET scans, increased tracer accumulation was observed in Paget disease of bone. Besides that Paget disease may mimic metastases on PET/CT using various radiotracers, including Ga-prostate-specific membrane antigen ligands and C-acetate, this case highlights the potential of multiparametric disease characterization on PET.

Evaluation of 68Ga-Glutamate Carboxypeptidase II Ligand Positron Emission Tomography for Clinical Molecular Imaging of Atherosclerotic Plaque Neovascularization

Objective—Intraplaque neovascularization contributes to the progression and rupture of atherosclerotic lesions. Glutamate carboxypeptidase II (GCPII) is strongly expressed by endothelial cells of tumor neovasculature and plays a major role in hypoxia-induced neovascularization in rodent models of benign diseases. We hypothesized that GCPII expression may play a role in intraplaque neovascularization and may represent a target for imaging of atherosclerotic lesions. The aim of this study was to determine frequency, pattern, and clinical correlates of vessel wall uptake of a 68Ga-GCPII ligand for positron emission tomographic imaging. Approach and Results—Data from 150 patients undergoing 68Ga-GCPII ligand positron emission tomography were evaluated. Tracer uptake in various arterial segments was analyzed and was compared with calcified plaque burden, cardiovascular risk factors, and immunohistochemistry of carotid specimens. Focal arterial uptake of 68Ga-GCPII ligand was identified at 5776 sites in 99.3% of patients. The prevalence of uptake sites was highest in the thoracic aorta; 18.4% of lesions with tracer uptake were colocalized with calcified plaque. High injected dose (P=0.0005) and obesity (P=0.007) were significantly associated with 68Ga-GCPII ligand accumulation, but other cardiovascular risk factors showed no association. The number of 68Ga-GCPII ligand uptake sites was significantly associated with overweight condition (P=0.0154). Immunohistochemistry did not show GCPII expression. Autoradiographic blocking studies indicated nonspecific tracer binding. Conclusions—68Ga-GCPII ligand positron emission tomography does not identify vascular lesions associated with atherosclerotic risk. Foci of tracer accumulation are likely caused by nonspecific tracer binding and are in part noise-related. Taken together, GCPII may not be a priority target for imaging of atherosclerotic lesions.

Screening of extravascular findings in pulmonary embolism computer tomography: 397 patients with 1950 non-pulmonary artery findings

Objectives The aim of this study was to investigate the possible benefits from computed tomography scans of patients with a suspected pulmonary artery embolism with a focus on relevant extravascular findings. Methods A total of 400 consecutive computed tomography pulmonary angiographies were evaluated. Computed tomography scans were analyzed in detail for the presence of pulmonary artery embolisms, as well as any other findings. Extra-artery discoveries were classified into none-relevant (Group A), intermediate (Group B), or relevant (Group C) findings. Results Aggregated computed tomography pulmonary angiographies detected other diagnosis than pulmonary artery embolism in 236 patients (59%). There were 1950 non-pulmonary artery embolism findings (4.9 per patient; n = 397). In the pulmonary artery embolism group, there were 447 extra-pulmonary artery embolism findings (5.2 per patient; n = 86) and in the non-pulmonary artery embolism group, 1503 findings (4.8 per patient; n = 311). Patients with pulmonary artery embolism had a significantly higher rate of pro-coagulate risk factors (p < 0.001). Conclusions Computed tomography pulmonary angiographies may help to identify further diagnoses. This study represents a retrospective review of a single center experience for incidental computed tomography findings during pulmonary artery embolism work-up and emphasizes the importance of analyzing the whole field-of-view.

Extra-vascular findings in patients undergoing magnetic resonance angiography of the abdomen, pelvis and lower extremities: A retrospective study of 352 patients

Background The aim of this study was to assess the prevalence and clinical significance of extra-vascular findings in patients undergoing magnetic resonance angiography of the abdomen, pelvis and lower extremities. Materials and methods Three hundred fifty-two patients underwent abdominal, pelvic and lower extremity 1.5 T magnetic resonance angiography. Clinically relevant vascular and extra-vascular findings were identified. Relevant vascular findings were classified as stenosis, occlusion, aneurysm, sclerosis, dissection or vasculitis. Relevant extra-vascular findings were categorized as ‘safe’ (Group A), intermediate – requiring additional investigation – (Group B) and malignant/endangering – requiring change of therapy (Group C). Results A total of 2152 clinically relevant vascular findings was identified (6.1/patient). The most frequent vascular finding was femoral artery stenosis (10.6%). Four hundred fifty-one extra-vascular findings were observed (1.3/patient) and classified into Group A (78%), Group B (19.5%) and Group C findings (2.4%). The most frequent malignant findings were lung cancer, lymphoma, osteosarcoma, hepatocellular carcinoma and renal cell carcinoma (7/352 patients). Conclusions Extravascular findings are frequently encountered in magnetic resonance angiography performed for vascular indications. Clinically relevant findings are seen in a substantial part of patients and should prompt further diagnostic work-up.

Participation of the spleen in the IgA immune response in the gut

The role of the spleen in the induction of an immune response to orally administered antigens is still under discussion. Although it is well known that after oral antigen administration specific germinal centres are not only formed in the Peyers patches (PP) and the mesenteric lymph nodes (mLN) but also in the spleen, there is still a lack of functional data showing a direct involvement of splenic B cells in an IgA immune response in the gut. In addition, after removal of mLN a high level of IgA+ B cells was observed in the gut. Therefore, in this study we analysed the role of the spleen in the induction of IgA+ B cells in the gut after mice were orally challenged with antigens. Here we have shown that antigen specific splenic IgM+ B cells after in vitro antigen stimulation as well as oral immunisation of donor mice were able to migrate into the gut of recipient mice, where they predominantly switch to IgA+ plasma cells. Furthermore, stimulation of recipient mice by orally administered antigens enhanced the migration of the splenic B cells into the gut as well as their switch to IgA+ plasma cells. Removal of the mLN led to a higher activation level of the splenic B cells. Altogether, our results imply that splenic IgM+ B cells migrate in the intestinal lamina propria, where they differentiate into IgA+ plasma cells and subsequently proliferate. In conclusion, we demonstrated that the spleen plays a major role in the gut immune response serving as a reservoir of immune cells that migrate to the site of antigen entrance.

Early Detection of Bilateral Testicular Metastases From Prostatic Adenocarcinoma Using 68Ga-PSMA Ligand PET/CT

We present the case of a 76-year-old man with biochemical relapse after primary therapy for prostate cancer. Ga prostate-specific membrane antigen (PSMA) ligand PET/CT performed for localization of recurrent disease revealed bilateral metastases to the testes. Histopathologic evaluation after bilateral orchiectomy revealed testicular metastases. Metastases to the testes are rare and usually seen in advanced stages. Ga-PSMA ligand PET/CT is a highly sensitive and specific imaging method for the detection of primary and metastatic prostate cancer and has refined diagnostic approaches. This case highlights the potential of PSMA-targeted PET/CT for detection of prostate cancer metastases, even in very unusual localizations.

99mTc-HMPAO perfusion SPECT/CT in the diagnosis of brain death

This report describes a case of brain death (BD) evaluated by 99mTc-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography/computed tomography (SPECT/CT). A 16-year-old boy with a history of rapid unexpected brain herniation due to pilocytic astrocytoma underwent 99mTc-HMPAO SPECT/CT for evaluation of brain death in the context of organ donation. Flow images demonstrated lack of blood flow to the brain, and delayed images showed absence of demonstrable radionuclide activity within the brain. SPECT/CT confirmed absence of tracer accumulation, and was deemed helpful for evaluation of the brain stem. 99mTc-HMPAO SPECT/CT is a valuable tool enabling imaging-based confirmation of BD.