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Introduction: The possible beneficial effects of physical activity during doxorubicin treatment of breast cancer need further investigation as many of the existing studies have been done on non-tumor-bearing models. Therefore, in this study, we aim to assess whether short-term voluntary wheel-running exercise during doxorubicin treatment of breast cancer-bearing mice could induce beneficial cardiac effects and enhance chemotherapy efficacy. Methods: Murine breast cancer I3TC cells were inoculated subcutaneously to the flank of female FVB mice (n = 16) that were divided into exercised and nonexercised groups. Two weeks later, doxorubicin treatment was started via intraperitoneal administration (5 mg/kg weekly for 3 weeks). Organs were harvested a day after the last dose. Results: The tumor volume over time was significantly different between the groups, with the exercising group having lower tumor volumes. The exercised group had increased body weight gain, tumor apoptosis, capillaries per cardiomyocytes, and cardiac lactate dehydrogenase activity compared to the unexercised group, but tumor blood vessel density and maturation and tumor and cardiac HIF1-a and VEGF-A levels did not differ from those of the nonexercised group. Discussion: We conclude that even short-term light exercise such as voluntary wheel running exercise can decrease the subcutaneous mammary tumor growth, possibly via increased tumor apoptosis. The increase in cardiac capillaries per cardiomyocytes may also have positive effects on cancer treatment outcomes. [ABSTRACT FROM AUTHOR]

Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive‐like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing, PET imaging, and gene expression analysis of Cry2−/− and Cry2+/+ mice. Compared to Cry2+/+ mice, we found that Cry2−/− mice spent less time immobile in the forced swim test, suggesting reduced despair‐like behavior. Moreover, Cry2−/− mice had lower saccharin preference, indicative of increased anhedonia. In contrast, we observed no group differences in anxiety‐like behavior. The behavioral changes were accompanied by lower metabolic activity of the ventro‐medial hypothalamus, suprachiasmatic nuclei, ventral tegmental area, anterior and medial striatum, substantia nigra, and habenula after cold stress as measured by PET imaging with a glucose analog. Although the expression of many depression‐associated and metabolic genes was upregulated or downregulated by cold stress, we observed no differences between Cry2−/− and Cry2+/+ mice. These findings are consistent with other studies showing that Cry2 is required for normal emotional behavior. Our findings confirm previous roles of Cry2 in behavior and extend them by showing that the effects on behavior may be mediated by changes in brain metabolism. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) with Gadolinium 1,4,7,10-tetraazacyclododecane-N',N″,N''',N″″-tetraacetic acid (Gd-DOTA) enables assessment of myocardial perfusion during first-pass of the contrast agent, while increased retention can signify areas of myocardial infarction (MI). We studied whether Gallium-68-labeled analog, 68Ga-DOTA, can be used to assess myocardial perfusion on positron emission tomography/computed tomography (PET/CT) in rats, comparing it with 11C-acetate.Methods: Rats were studied with 11C-acetate and 68Ga-DOTA at 24 hours after permanent ligation of the left coronary artery or sham operation. One-tissue compartmental models were used to estimate myocardial perfusion in normal and infarcted myocardium. After the PET scan, hearts were sectioned for autoradiographic detection of 68Ga-DOTA distribution.Results: 11C-acetate PET showed perfusion defects and histology showed myocardial necrosis in all animals after coronary ligation. Kinetic modeling of 68Ga-DOTA showed significantly higher k1 values in normal myocardium than in infarcted areas. There was a significant correlation (r = 0.82, P = 0.001) between k1 values obtained with 68Ga-DOTA and 11C-acetate. After 10 minutes of tracer distribution, the 68Ga-DOTA concentration was significantly higher in the infarcted than normal myocardium on PET imaging and autoradiography.Conclusions: Our results indicate that acute MI can be detected as reduced perfusion, as well as increased late retention of 68Ga-DOTA. [ABSTRACT FROM AUTHOR]

There may be some differences in the in vivo behavior of 68Ga-chloride and 68Ga-citrate leading to different accumulation profiles. This study compared 68Ga-citrate and 68Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n=32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using 68Ga-citrate or 68Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of 68Ga-chloride and 68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher (P=0.0019 and P=0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, the SUVmax of 68Ga-citrate was significantly higher than the uptake of 68Ga-chloride (P=0.0017). In animals with uncomplicated bone healing, no difference in the SUVmax of 68Ga-chloride or 68Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of 68Ga-citrate for PET imaging of osteomyelitis. [ABSTRACT FROM AUTHOR]

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1).We compared 68Ga-DOTA- and 18F-fluorodeoxyribose-(FDR-) labeled Siglec-9motif peptides for PET imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry fromthe rat data. Results. In rats, 68Ga-DOTA-Siglec-9 (SUV, 0.88 ± 0.087) and 18F-FDR-Siglec-9 (SUV, 0.77 ± 0.22) showed comparable (P = 0.29) imaging of inflammation. In atherosclerotic mice, 18FFDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6 ± 0.078) similar to previously tested 68Ga-DOTASiglec-9 (P = 0.35).Human effective dose estimates for 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9were 0.024 and 0.022 mSv/MBq, respectively. Conclusion. Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68Ga-DOTA-Siglec-9 present advantages over 18F-FDR-Siglec-9, indicating it as a primary choice for clinical studies. [ABSTRACT FROM AUTHOR]

A correction to the article "Absorption, distribution and excretion of intravenously injected Ge68/Ga68 generator eluate in healthy rats, and estimation of human radiation dosimetry," by Anu Autio et al, published in previous issue is presented.

Background: This study evaluated the absorption, distribution, and excretion of Gallium-68 (Ga) radionuclide after a single intravenous (i.v.) injection of Ge/Ga generator eluate in healthy rats. Additionally, human radiation doses were estimated from the rat data. Methods: Twenty-one female and 21 male Sprague-Dawley rats were i.v. injected with 47 ± 4 MBq of Ge/Ga generator eluate, and the radioactivity of excised organs was measured using a gamma counter at 5, 30, 60, 120, or 180 min afterwards ( n = 3-7 for each time point). The radioactivity concentration and plasma pharmacokinetic parameters were calculated. Subsequently, the estimates for human radiation dosimetry were determined. Additionally, 4 female and 5 male rats were positron emission tomography (PET) imaged for in vivo visualization of biodistribution. Results: Ga radioactivity was cleared relatively slowly from blood circulation and excreted into the urine, with some retention in the liver and spleen. Notably, the Ga radioactivity in female genital organs, i.e., the uterus and ovaries, was considerable higher compared with male genitals. Extrapolating from the female and male rat Ga data, the estimated effective dose was 0.0308 mSv/MBq for a 57-kg woman and 0.0191 mSv/MBq for a 70-kg man. Conclusions: The estimated human radiation burden of the Ge/Ga generator eluate was slightly higher for females and similar for males as compared with somatostatin receptor ligands Ga-DOTANOC, Ga-DOTATOC, and Ga-DOTATATE, which is probably due to the retention in the liver and spleen. Our results revealed some differences between female and male rat data, which, at least in part, may be explained by the small sample size. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET) with O-labeled water (HO) facilitates the visualization and quantification of blood flow in clinical investigations and also in small animals. The quantification of blood flow requires an input function, which is generally obtained by measuring radioactivity in arterial blood withdrawn during PET scanning. However, this approach is not always feasible, because abundant blood sampling may affect the physiological process being measured. The purpose of the present study was to develop and cross-validate two methods, namely, a blood- and an image-based method for obtaining the input function for blood flow studies from rat HO PET. Methods: The study material consisted of two separate groups of rats. Group 1 rats were imaged twice by a high-resolution research tomograph PET camera at resting condition for a test-retest study ( n = 4), and group 2 rats were imaged with and without adenosine infusion for a rest-stress study ( n = 4). In group 1, radioactivity concentration in arterial blood was measured with a new flow-through detector during imaging and a blood-based input function was obtained. The image-based input function was estimated using time-activity curves from the left ventricle and myocardial regions. To validate the two input function methods, myocardial blood flow (MBF) and cerebral blood flow (CBF) were computed, and the methods were tested for reproducibility (test-retest study) and changes (rest-stress study). Results: The blood- and image-based input functions were similar, and the corresponding CBF values differed only by −6.9 ± 8.1%. In the test-retest study, both MBF and CBF showed good reproducibility, and in the rest-stress study, adenosine significantly increased both MBF ( P = 0.035) and CBF ( P = 0.029), compared with the resting condition. Conclusion: It is possible both to measure the input function from rat arteria femoralis during HO PET imaging and to estimate the input function from rat HO PET images, thereby facilitating the assessment of blood flow in organs visible in PET images. [ABSTRACT FROM AUTHOR]