[en] Dynamic interactions between tumor cells and immune cells promote the initiation, progression, metastasis and therapy-resistance of cancer. With respect to immunotherapy, immune cell populations such as cytotoxic CD8⁺ T-cells, CD56⁺ NK cells and myeloid phagocytic cells play decisive roles. From an imaging perspective, the immune system displays unique challenges, which have implications for the design and performance of studies. The immune system comprises highly mobile cells that undergo distinct phases of development and activation. These cells circulate through several compartments during their active life span and accumulate in rather limited numbers in cancer lesion, where their effector phenotype further diversifies. Given these features, accurate evaluation of the tumor microenvironment and its cellular components during anti-cancer immunotherapy is challenging. In-vivo imaging currently offers quantitative and sensitive modalities that exploit long-lived tracers to interrogate, e.g. distinct immune cell populations, metabolic phenotypes, specific targets relevant for therapy or critical for their effector function. This review provides a comprehensive overview of current status for in-vivo imaging tumor-infiltrating immune cell populations, focusing on lymphocytes, NK cells and myeloid phagocytic cells, with emphasis on clinical translation.

[en] The aim of this retrospective study was to compare the targeting of “pure” osteomyelitis (i.e., without surrounding soft tissue infection) by directly 99mTc-labelled complete immunoglobulin G (IgG) monoclonal antibody (MAb) ([99mTc]besilesomab) and by directly 99mTc-labelled fragment antigen-binding (FAb) MAb ([99mTc]sulesomab) in relation to their kinetic fate. A total of 73 patients with “pure” osteomyelitis were examined with [99mTc]besilesomab, (Scintimun®, IBA/CIS bio international, Saclay, France; N.=38) and [99mTc]sulesomab (LeukoScan®, Immunomedics Inc., Morris Plains, NJ, USA; N.=35). Kinetic data were deduced from whole-body and single-photon emission computed tomographic scans, performed 10 minutes to 24 hour p.i. (region-of-interest technique [ROI]). In targeting “pure” osteomyelitis, sensitivities at 1-4 hours were found to be higher for [99mTc]sulesomab (44% and 80% for [99mTc]besilesomab and [99mTc]sulesomab, respectively) but at significantly lower target/background (T/B) ratios than with [99mTc]besilesomab (1.8±0.3 versus 1.4±0.5 for [99mTc]besilesomab and [99mTc]sulesomab respectively; P<0.01). With [99mTc]besilesomab, there was a continuous osteomyelitis uptake over 24 hours, whereas with [99mTc]sulesomab, the maximal uptake occurred mostly within 1-4 hours, with subsequent clearance being slower for antigen-bound activity than for nonspecific background. Hence, diagnosis was possible mostly after 4h with [99mTc]sulesomab but often not before 24 hours with [99mTc]besilesomab, the later increasing significantly (P<0.01) in sensitivity (87% and 84% for [99mTc]besilesomab and [99mTc]sulesomab, respectively). These results show that the higher sensitivity of [99mTc]sulesomab in osteomyelitis targeting at earlier p.i. times does not rely on an increased antibody uptake but on a more rapid clearance of nonspecific background activity due to faster metabolism and excretion. Intact [99mTc]besilesomab show a slow, continuous uptake, leading to higher T/B at later p.i. times, often beyond the imaging possibilities of 99mTc.

[en] This review article highlights the role of radiological and nuclear medicine techniques in diagnosis of musculoskeletal infections with particular regard to hybrid imaging of osteomyelitis, prosthetic joint infections, sternal infections and spine infections. Authors conclude on the complementary role of the several techniques with indications for an appropriate diagnostic flow chart, in the light of the recent European Association of Nuclear Medicine guidelines on infection.

[en] Cholecystokinin subtype 2 receptors (CCK2R) are over expressed in several human cancers, including medullary thyroid carcinoma. Gastrin and cholecystokinin (CCK) peptides that bind with high affinity and specificity to CCK2R can be used as carriers of radioactivity to CCK2R-expressing tumor sites. Several gastrin and CCK related peptides have been proposed for diagnostic imaging and radionuclide therapy of primary and metastatic CCK2R-positive human tumors. Their clinical application has been restricted to a great extent by their fast in vivo degradation that eventually compromises tumor uptake. This problem has been addressed by structural modifications of gastrin and CCK motifs, which, however, often lead to suboptimal pharmacokinetic profiles. A major enzyme implicated in the catabolism of gastrin and CCK based peptides is neutral endopeptidase (NEP), which is widely distributed in the body. Coinjection of the NEP inhibitor phosphoramidon (PA) with radiolabeled gastrin and other peptide analogs has been recently proposed as a new promising strategy to increase bioavailability and tumor-localization of radiopeptides in tumor sites. Specifically, co-administration of PA with the truncated gastrin analog [111In-DOTA]MG11 ([(111In-DOTA)DGlu10]gastrin(10-17)) impressively enhanced the levels of intact radiopeptide in mouse circulation and has led to an 8-fold increase of CCK2R-positive tumor uptake in SCID mice. This increased tumor uptake, visualized also by SPECT/CT imaging, is expected to eventually translate into higher diagnostic sensitivity and improved therapeutic efficacy of radiolabeled gastrin analogs in CCK2R-expressing cancer patients.

[en] The development of novel radiopharmaceutical agents for imaging and therapy of neoplastic diseases relies on accurate and reproducible animal models. Rodent models are often used to demonstrate the proof-of-principle tracer and therapeutic agent development, but their small size can make tissue sampling challenging. The dosimetry of decay emissions in the much smaller rodent tumors do not model dosimetry in human tumors well. In addition, rodent models of cancer represent a simplified version of a very complex process. Spontaneous tumors are heterogenous and the response to intervention can be unpredictable; tumor cells can adopt alternate signaling pathways and modify their interaction with the microenvironment. These inconsistencies, while present in humans, are difficult to fully reproduce in a genetically-engineered rodent model. Companion animals, primarily dogs and cats, offer translational models that more accurately reflect the intricate nature of spontaneous neoplasia in humans. Their larger size facilitates tissue and blood sampling when needed, and allows radiopharmaceutical tracers to be studied on human-scale imaging systems to better mimic the clinical application of the agent. This article will review the growing body of literature surrounding the use of radiopharmaceutical agents for both imaging and therapy in companion dogs and cats. Previous investigations have been performed both for the advancement of routine, high-level veterinary care, and in the context of translational research from which the results of imaging and treatment can be readily applied to people. Studies utilizing the spontaneously occurring cancer model in companion animals involving positron emission tomography, radiotracers, dosimetry, theranostics, targeted radiopharmaceuticals, brachytherapy, and boron neutron capture therapy are discussed.

[en] Preoperative detection of extranodal spread (ENS) in head and neck cancer can have important consequences for patient management. The aim of this study was to determine whether 18-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) or a combination with Magnetic Resonance Imaging (MRI) could more accurately predict ENS, especially with the near availability of fully integrated [18F]FDG PET/MRI scanners. In retrospective cohort design a total of twelve patients, with 18 lymphnode metastases were studied with [18F]FDG PET and MRI. Presence of ENS was scored on MRI, and [18F]FDG PET images using a SUV max cut-off point of 12. Histopathology results were used as reference standard. Sensitivity, specificity and accuracy were calculated. The sensitivity, specificity and accuracy of [18F]FDG PET for ENS reached 70%,100% and 83%, respectively. The mean SUVmax of ENS positive lymphnodes was 13.6 versus 8.7 for lymphnode metastases without ENS (P=0.03). The sensitivity, specificity and accuracy of MRI for ENS were 70%, 100% and 83%, respectively. When the [18F]FDG PET and MRI findings were combined sensitivity, specificity and accuracy were 80%, 100% and 89%, respectively. Thus, accuracy increased from 83% to 89%. When there is no ENS or doubt of ENS on MRI, [18F]FDG PET seems to have additional value since it improves sensitivity and resolves uncertainty in case of high FDG uptake. This benefit needs to be confirmed prospectively in a larger cohort.

[en] It is investigated the relationship between ¹⁸F-FDG PET parameters and apparent diffusion coefficient (ADC) values obtained by diffusion weighted MRI (DWI) in patients with invasive ductal carcinoma (IDC). In addition, the prognostic utility of PET/MR mammography parameters was compared with that of known histologic prognostic factors. Forty-six women aged 50.7±10.5 years underwent a preoperative PET/MR mammography assessment using an integrated PET/MR scanner. T1w, T2w, DWI (b value: 50, 400, and 800 s/mm2), dynamic contrast enhancement sequences, and ¹⁸F-FDG PET imaging were performed. IDCs were assessed using SUVmax values and intratumoral heterogeneities (IH) from the ¹⁸F-FDG PET images and mean (ADCmean) and minimum ADC (ADCmin) values were measured using the DWI images. Relationships between the PET parameters and ADC values were evaluated. Furthermore, SUVmax and ADC values were compared with histologic factors, tumor size, nodal status, lymphovascular invasion, Ki-67 expression and triple negative breast cancer (TNBC). In total 46 IDCs (2.1-7.5 cm in size) were analyzed. SUVmax (P=0.012) and elevated IH (P=0.041) were negatively correlated with ADCmin, then TNBC (P=0.013) and high Ki-67 expression (P=0.002) were associated with higher SUVmax. IDC with lymphovascular invasion had low ADCmin values (P=0.045). In conclusion, ¹⁸F-FDG PET metabolic parameters and ADCmin were negatively correlated. PET parameters and ADC values might reflect the expression of biological features of tumors and tumor invasiveness, respectively. Integrated PET/MR mammography seemed like to have potential of a one-stop method for evaluating and predicting the prognosis of IDC.

[en] Over the last several decades, radionuclide Myocardial Perfusion Imaging (MPI) has been a mainstay for the evaluation of coronary artery disease (CAD), based on the assumption that a detailed knowledge of stenosis localization and severity is not sufficient for clinical decision making. Furthermore, radionuclide MPI diagnostic accuracy has been implemented by the assessment of Coronary Flow Reserve (CFR) and Myocardial Blood Flow (MBF), as quantitative indexes of stenosis severity and surrogates of total ischaemic burden. Several considerations indicate that these measurement actually improve description of coronary physiology with respect to conventional qualitative image analysis. However, several alternative approaches have been optimized and increasingly proposed to achieve this task in the clinical setting. The aim of the present narrative review is to discuss strengths and weaknesses of the various cardiac modalities proposed to define CFR and MBF in the era of multi-modality imaging.

[en] Patients with hypertension may exhibit abnormal vasodilator capacity during pharmacological vasodilatation. We assessed coronary flow reserve (CFR) by sestamibi imaging in hypertensive patients with normal coronary vessels. Twenty-five patients with untreated mild essential hypertension and normal coronary vessels and 10 control subjects underwent dipyridamole-rest Tc-99m sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first transit counts in pulmonary artery and myocardial counts from tomograhic images. CFR was expressed as the ratio of stress to rest MBF. Coronary vascular resistances (CVR) were computed as the ratio between mean arterial pressure and MBF. Estimated MBF at rest was not different in patients and controls (1.11±0.59 vs. 1.14±0.28 counts/pixel/s; P=0.87). Conversely, stress MBF was lower in patients than in controls (1.55±0.47 vs. 2.68±0.53 counts/pixel/s; P<0.001). Thus, CFR was reduced in patients compared to controls (1.61±0.58 vs. 2.43±0.62; P<0.001). Rest and stress CVR values were higher in patients (P<0.001), while stress-induced changes in CVR were not different (P=0.08) between patients (-51%) and controls (-62%). In the overall study population, a significant relation between CFR and stress-induced changes in CVR was observed (r=-0.86; P<0.001). Sestamibi imaging may detect impaired coronary vascular function in response to dipyridamole in patients with untreated mild essential hypertension and normal coronary arteries. A mild increase in arterial blood pressure does not affect baseline MBF, but impairs coronary reserve due to the amplified resting coronary resistances.

[en] In the setting of hypertrophic cardiomyopathy (HCM), ischemia plays a possibly under-evaluated role. In particular, a large body of evidence indicates that structural and functional abnormalities in the coronary microcirculation contribute to myocardial ischemia and are key elements for HCM pathophysiology and clinical evolution. Measurement of myocardial blood flow (MBF) at rest and under maximal hyperemia (hMBF) by means of perfusion positron-emission tomography (PET) is the most effective way to assess microvascular dysfunction in humans. Therefore, hMBF abnormalities reflect HCM severity and correlate with other important features, such as ischemic symptoms and myocardial fibrosis. Most importantly, it has been demonstrated that severely blunted hMBF implies an adverse outcome in HCM patients. Therefore, PET could be helpful for stratifying patient prognosis and should be used in selected patient subsets to identify those at risk of unfavorable evolution.