KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [⁶⁷Ga]KP46 and [⁶⁸Ga]KP46, compared with [⁶⁸Ga]gallium acetate, were used for logP measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. ⁶⁸Ga was more efficiently accumulated in A375 cells in vitro when presented as [⁶⁸Ga]KP46 than as [⁶⁸Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [^68/67Ga]KP46, absorption of ⁶⁸Ga and ⁶⁷Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone.

Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([⁶⁸Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [⁶⁸Ga]Ga-SKN by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and S. epidermidis, but no uptake by Candida glabrata, C. albicans, or Aspergillus fumigatus, demonstrated its specificity to bacterial species. Whole-body [⁶⁸Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [⁶⁸Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.

Radioactive isotopes of elements from across the periodic table allow for non-invasive imaging of essential metals in health and disease.

The hippocampus plays a significant role in learning, memory encoding, and spatial navigation. Typically, the hippocampus is investigated as a whole region of interest. However, recent work has developed fully detailed atlases based on cytoarchitecture properties of brain regions, and the hippocampus has been sub-divided into seven sub-areas that have structural differences in terms of distinct numbers of cells, neurons, and other structural and chemical properties. Moreover, gender differences are of increasing concern in neuroscience research. Several neuroscience studies have found structural and functional variations between the brain regions of females and males, and the hippocampus is one of these regions. The aim of this study to explore whether the cytoarchitecturally distinct sub-regions of the hippocampus have varying patterns of functional connectivity with different networks of the brain and how these functional connections differ in terms of gender differences. This study investigated 200 healthy participants using seed-based resting-state functional magnetic resonance imaging (rsfMRI). The primary aim of this study was to explore the resting connectivity and gender distinctions associated with specific sub-regions of the hippocampus and their relationship with major functional brain networks. The findings revealed that the majority of the seven hippocampal sub-regions displayed functional connections with key brain networks, and distinct patterns of functional connectivity were observed between the hippocampal sub-regions and various functional networks within the brain. Notably, the default and visual networks exhibited the most consistent functional connections. Additionally, gender-based analysis highlighted evident functional resemblances and disparities, particularly concerning the anterior section of the hippocampus. This study highlighted the functional connectivity patterns and involvement of the hippocampal sub-regions in major brain functional networks, indicating that the hippocampus should be investigated as a region of multiple distinct functions and should always be examined as sub-regions of interest. The results also revealed clear gender differences in functional connectivity.

Background: 99mTc-MIBI is a lipophilic cation that can accumulate within the mitochondria of metabolically active tumor cells and is routinely used for parathyroid and myocardial perfusion imaging. Cases of incidental findings during parathyroid scintigraphy and myocardial perfusion scans using 99mTc-MIBI have been reported previously. However, retrospective studies with more extensive sample data are lacking. Objectives: This observational study retrospectively analyzed 99mTc- MIBI parathyroid and myocardial perfusion images to describe incidental extra-parathyroid and cardiac uptake. Methods: A retrospective review of 308 parathyroid and myocardial perfusion 99mTc-MIBI scans was performed between January 2019 and December 2022. 99mTc-pertechnetate with 99mTc-MIBI was used in parathyroid cases to delineate thyroid-related abnormalities. The raw projection data, acquired images, and patients’ medical and laboratory records were assessed. Results: Out of 308 scans, eight were identified with incidental extracardiac and parathyroid findings during data interpretation. Three incidental findings were noted in the parathyroid scans, specifically in the right parotid gland, right submandibular gland, and the fifth right rib. The use of 99mTc-pertechnetate alongside 99mTc-MIBI facilitated the visualization and comparison of incidental finding biodistribution in the parathyroid cases. Additionally, five incidental findings were detected in the cardiac stress raw projection data, located in the breast area, axillary lymph nodes, and lungs. All extracardiac incidental findings were observed in the stress data, attributed to the higher dose administered post-stress compared to the rest of the study. Conclusion: Thorough screening of images and raw projection data is vital to prevent the progression of unknown abnormalities and ensure significant findings are not overlooked.

Background/Objectives: Early diagnosis of cardiac amyloidosis is crucial to improve patient outcomes. Although ^99mTc-MDP is less sensitive than other bone-avid tracers for detecting ATTR-CA, it is widely used for routine bone imaging in this region. Incidental cardiac uptake on ^99mTc-MDP bone scintigraphy may therefore offer a practical opportunity for identifying suspected ATTR-CA in resource-limited settings. To evaluate incidental cardiac uptake, warranting further evaluation for ATTR-CA on routine ^99mTc-MDP bone scans as an incidental flag method for patients who require further evaluation and to propose a referral pathway in resource-limited settings. Methods: A retrospective review of 229 patients was performed. The assessment of myocardial uptake was performed using the Perugini visual score and H/CL ratio analysis. Patients’ medical records were reviewed, and available cardiac imaging reports were evaluated for further assessment of cardiac involvement. Results: Nine patients demonstrated a Perugini score = 2; of these, five underwent echocardiography, demonstrating abnormalities that may indicate amyloid involvement. No patient had confirmatory ATTR-CA testing, AL-CA exclusion testing, (CMR), biopsy, or amyloid typing. In patients without prior cardiac disease, echocardiographic abnormalities may potentially represent subclinical disease, such as cardiac amyloidosis, though this requires further confirmation. In patients with HTN or diabetes, the echocardiographic changes may be attributed to the underlying conditions. Echocardiographic characteristics suggestive, but not specific, for cardiac amyloidosis were observed in patients selected based on positive ^99mTc-MDP uptake. Conclusions: Incidental cardiac uptake with a Perugini score ≥ 2 can highlight patients for ATTR-CA investigation. These results provide preliminary evidence that incidental ^99mTc-MDP cardiac uptake can flag patients who require further evaluation for ATTR-CA and support the implementation of a referral pathway from local evaluation to a specialized center.