Background: Metabolic syndrome and its individual components lead to wide-ranging consequences, many of which affect the central nervous system. In this study, we compared the [¹⁸F]FDG regional brain metabolic pattern of participants with type 2 diabetes mellitus (T2DM) and non-DM obese individuals. Methods: In our prospective study, 51 patients with controlled T2DM (ages 50.6 ± 8.0 years) and 45 non-DM obese participants (ages 52.0 ± 9.6 years) were enrolled. Glucose levels measured before PET/CT examination (pre-PET glucose) as well as laboratory parameters assessing glucose and lipid status were determined. NeuroQ application (NeuroQ^TM 3.6, Syntermed, Philips) was used to evaluate regional brain metabolic differences. [¹⁸F]FDG PET/CT (AnyScan PC, Mediso) scans, estimating brain metabolism, were transformed to MNI152 brain map after T1 registration and used for SPM-based group comparison of brain metabolism corrected for pre-PET glucose, and correlation analysis with laboratory parameters. Results: NeuroQ analysis did not reveal significant regional metabolic defects in either group. Voxel-based group comparison revealed significantly (P_FWE<0.05) decreased metabolism in the region of the precuneus and in the right superior frontal gyrus (rSFG) in the diabetic group as compared to the obese patients. Data analysis corrected for pre-PET glucose level showed a hypometabolic difference only in the rSFG in T2DM. Voxel-based correlation analysis showed significant negative correlation of the metabolism in the following brain regions with pre-PET glucose in diabetes: precuneus, left posterior orbital gyrus, right calcarine cortex and right orbital part of inferior frontal gyrus; whilst in the obese group only the right rolandic (pericentral) operculum proved to be sensitive to pre-PET glucose level. Conclusions: To our knowledge, this is the first study to perform pre-PET glucose level corrected comparative analysis of brain metabolism in T2DM and obesity. We also examined the pre-PET glucose level dependency of regional cerebral metabolism in the two groups separately. Large-scale future studies are warranted to perform further correlation analysis with the aim of determining the effects of metabolic disturbances on brain metabolism.

Angiogenesis plays a crucial role in tumour progression and metastatic spread; therefore, the development of specific vectors targeting angiogenesis has attracted the attention of several researchers. Since angiogenesis-associated aminopeptidase N (APN/CD13) is highly expressed on the surface of activated endothelial cells of new blood vessels and a wide range of tumour cells, it holds great promise for imaging and therapy in the field of cancer medicine. The selective binding capability of asparagine-glycine-arginine (NGR) motif containing molecules to APN/CD13 makes radiolabelled NGR peptides promising radiopharmaceuticals for the non-invasive, real-time imaging of APN/CD13 overexpressing malignancies at the molecular level. Preclinical small animal model systems are major keystones for the evaluation of the in vivo imaging behaviour of radiolabelled NGR derivatives. Based on existing literature data, several positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radioisotopes have been applied so far for the labelling of tumour vasculature homing NGR sequences such as Gallium-68 (⁶⁸Ga), Copper-64 (⁶⁴Cu), Technetium-99m (^99mTc), Lutetium-177 (¹⁷⁷Lu), Rhenium-188 (¹⁸⁸Re), or Bismuth-213 (²¹³Bi). Herein, a comprehensive overview is provided of the recent preclinical experiences with radiolabelled imaging probes targeting angiogenesis.

Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific binding to tumor-related antigens and cell surface receptors. Although earlier studies have already demonstrated the anti-tumor potential of alpha-emitting radium (Ra) isotopes—Radium-223 and Radium-224 (^223/224Ra)—in the treatment of skeletal metastases, their inability to complex with target-specific moieties hindered application beyond bone targeting. To exploit the therapeutic gains of Ra across a wider spectrum of cancers, nanoparticles have recently been embraced as carriers to ensure the linkage of ^223/224Ra to target-affine vectors. Exemplified by prior findings, Ra was successfully bound to several nano/microparticles, including lanthanum phosphate, nanozeolites, barium sulfate, hydroxyapatite, calcium carbonate, gypsum, celestine, or liposomes. Despite the lengthened tumor retention and the related improvement in the radiotherapeutic effect of ^223/224Ra coupled to nanoparticles, the in vivo assessment of the radiolabeled nanoprobes is a prerequisite prior to clinical usage. For this purpose, experimental xenotransplant models of different cancers provide a well-suited scenario. Herein, we summarize the latest achievements with ^223/224Ra-doped nanoparticles and related advances in targeted alpha radiotherapy.

Angiogenesis-related cell-surface molecules, including integrins, aminopeptidase N, vascular endothelial growth factor, and gastrin-releasing peptide receptor (GRPR), play a crucial role in tumour formation. Radiolabelled imaging probes targeting angiogenic biomarkers serve as valuable vectors in tumour identification. Nowadays, there is a growing interest in novel radionuclides other than gallium-68 (⁶⁸Ga) or copper-64 (⁶⁴Cu) to establish selective radiotracers for the imaging of tumour-associated neo-angiogenesis. Given its ideal decay characteristics (E_β⁺_average: 632 KeV) and a half-life (T_1/2 = 3.97 h) that is well matched to the pharmacokinetic profile of small molecules targeting angiogenesis, scandium-44 (⁴⁴Sc) has gained meaningful attention as a promising radiometal for positron emission tomography (PET) imaging. More recently, intensive research has been centered around the investigation of ⁴⁴Sc-labelled angiogenesis-directed radiopharmaceuticals. Previous studies dealt with the evaluation of ⁴⁴Sc-appended a_vb₃ integrin–affine Arg-Gly-Asp (RGD) tripeptides, GRPR-selective aminobenzoyl–bombesin analogue (AMBA), and hypoxia-associated nitroimidazole derivatives in the identification of various cancers using experimental tumour models. Given the tumour-related hypoxia- and angiogenesis-targeting capability of these PET probes, ⁴⁴Sc seems to be a strong competitor of the currently used positron emitters in radiotracer development. In this review, we summarize the preliminary preclinical achievements with ⁴⁴Sc-labelled angiogenesis-specific molecular probes.

Background: Cerebral blood flow abnormalities are supposed to be potential risk factors for developing cognitive dysfunction in the general population. Aging, obesity and type 2 diabetes mellitus are associated with perfusion abnormalities leading to cognitive impairment, neurodegeneration and future development of dementia. In our study, we aimed at identifying independent factors that contribute to the appearance of regional brain perfusion changes besides those that are already known. Material and methods: Forty-three type 2 diabetic and twenty-six obese patients were enrolled. After the intravenous administration of 740 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO), all subjects underwent brain perfusion SPECT imaging applying AnyScan S Flex dual-head gamma camera (Mediso, Hungary). Using Philips Achieva 3T scanner brain resting-state functional MRI was also performed. The SPECT and MRI images were co-registered and transformed to the MNI152 atlas space so that data of the following standard volumes of interest (VOIs) could be obtained: frontal lobe, parietal lobe, temporal lobe, occipital lobe, limbic region, cingulate, insula, basal ganglia, cerebrum, limbic system and brain stem. Using the SPSS 25 statistical software package, general linear regression analysis, Student’s t-test, and Mann-Whitney U-test were applied for statistical analyses. Results: Multivariate linear analysis identified that BMI and age are significantly (p < 0.0001) associated with perfusion, and patient group was slightly above threshold (p = 0.0524). We also found that the presence of diabetes was an independent significant predictor of normalized regional brain perfusion only in the insula (p < 0.001). Other independent predictors of normalized regional brain perfusion were: age in the insula (p < 0.001) and in the limbic region (p < 0.01), and BMI in the brain stem (p < 0.01). Conclusions: Age and BMI proved to be general, and diabetes regional predictor of brain hypoperfusion. BMI appeared to be a novel factor affecting brain perfusion. In one specific region, the insula, we detected a difference between the obese and the diabetic group. These findings may be significant in the understanding of the development of cognitive impairment in metabolic diseases. Background: Cerebral blood flow abnormalities are supposed to be potential risk factors for developing cognitive dysfunction in the general population. Aging, obesity and type 2 diabetes mellitus are associated with perfusion abnormalities leading to cognitive impairment, neurodegeneration and future development of dementia. In our study, we aimed at identifying independent factors that contribute to the appearance of regional brain perfusion changes besides those that are already known. Material and methods: Forty-three type 2 diabetic and twenty-six obese patients were enrolled. After the intravenous administration of 740 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO), all subjects underwent brain perfusion SPECT imaging applying AnyScan S Flex dual-head gamma camera (Mediso, Hungary). Using Philips Achieva 3T scanner brain resting-state functional MRI was also performed. The SPECT and MRI images were co-registered and transformed to the MNI152 atlas space so that data of the following standard volumes of interest (VOIs) could be obtained: frontal lobe, parietal lobe, temporal lobe, occipital lobe, limbic region, cingulate, insula, basal ganglia, cerebrum, limbic system and brain stem. Using the SPSS 25 statistical software package, general linear regression analysis, Student’s t-test, and Mann-Whitney U-test were applied for statistical analyses. Results: Multivariate linear analysis identified that BMI and age are significantly (p < 0.0001) associated with perfusion, and patient group was slightly above threshold (p = 0.0524). We also found that the presence of diabetes was an independent significant predictor of normalized regional brain perfusion only in the insula (p < 0.001). Other independent predictors of normalized regional brain perfusion were: age in the insula (p < 0.001) and in the limbic region (p < 0.01), and BMI in the brain stem (p < 0.01). Conclusions: Age and BMI proved to be general, and diabetes regional predictor of brain hypoperfusion. BMI appeared to be a novel factor affecting brain perfusion. In one specific region, the insula, we detected a difference between the obese and the diabetic group. These findings may be significant in the understanding of the development of cognitive impairment in metabolic diseases.

Since angiogenesis/neoangiogenesis has a major role in tumor development, progression and metastatic spread, the establishment of angiogenesis-targeting imaging and therapeutic vectors is of utmost significance. Aminopeptidase N (APN/CD13) is a pivotal biomarker of angiogenic processes abundantly expressed on the cell surface of active vascular endothelial and various neoplastic cells, constituting a valuable target for cancer diagnostics and therapy. Since the asparagine–glycine–arginine (NGR) sequence has been shown to colocalize with APN/CD13, the research interest in NGR-peptide-mediated vascular targeting is steadily growing. Earlier preclinical experiments have already demonstrated the imaging and therapeutic feasibility of NGR-based probes labeled with different positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radionuclides, including Gallium-68 (⁶⁸Ga), Copper-64 (⁶⁴Cu), Technetium-99m (^99mTc), Lutetium-177 (¹⁷⁷Lu), Rhenium-188 (¹⁸⁸Re) or Bismuth-213 (²¹³Bi). To improve the tumor binding affinity and the retention time of single-receptor targeting peptides, NGR motifs containing heterodimers have been introduced to identify multi-receptor overexpressing malignancies. Preclinical studies with various tumor-bearing experimental animals provide useful tools for the investigation of the in vivo imaging behavior of NGR-based heterobivalent ligands. Herein, we review the reported preclinical achievements on NGR heterodimers that could be highly relevant for the development of further target-specific multivalent compounds in diagnostic and therapeutic settings.