Physiological Uptake Research Articles

The avian retroviral receptor Tva mediates the uptake of transcobalamin bound vitamin B12 (cobalamin).

The Avian sarcoma and leukosis viruses (ASLVs) are important chicken pathogens. Some of the virus subgroups, including ASLV-A and K, utilize the Tva receptor for cell entrance. Though Tva was identified three decades ago, its physiological function remains unknown. Previously, we have noted an intriguing resemblance and orthology between the chicken gene coding for Tva and the human gene coding for CD320, a receptor involved in cellular uptake of transcobalamin (TC) in complex with vitamin B12/cobalamin (Cbl).Here we show that both the transmembrane and the glycosylphosphatidylinositol (GPI)-anchored form of Tva in the chicken cell line DF-1 promotes the uptake of Cbl with help of expressed and purified chicken TC. The uptake of TC-Cbl complex was monitored using an isotope- or fluorophore-labeled Cbl. We show that (i) TC-Cbl is internalized in chicken cells; and (ii) the uptake is lower in the Tva-knockout cells and higher in Tva-overexpressing cells when compared with wild type chicken cells. The relation between physiological function of Tva and its role in infection was elaborated by showing that infection with ASLV subgroups (targeting Tva) impairs the uptake of TC-Cbl, while this is not the case for cells infected with ASLV-B (not recognized by Tva). In addition, exposure of the cells to a high concentration of TC-Cbl alleviates the infection with Tva-dependent ASLV.IMPORTANCE: We demonstrate that the ASLV receptor Tva participates in the physiological uptake of TC-Cbl, because the viral infection suppresses the uptake of Cbl and vice versa. Our results pave the road for future studies addressing the issues: (i) whether a virus infection can be inhibited by TC-Cbl complexes in vivo; and (ii) whether any human virus employs the human TC-Cbl receptor CD320. In broader terms, our study sheds light on the intricate interplay between physiological roles of cellular receptors and their involvement in virus infection.

FAPI-04 PET/CT Using [18F]AlF Labeling Strategy: Automatic Synthesis, Quality Control, and In Vivo Assessment in Patient.

68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0–7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.

Characterisation of 99mTc EDDA/HYNIC-TOC (Tektrotyd) physiological and neuroendocrine tumour uptake using SPECT/CT standardised uptake values: initial experience.

99mTc Ethylene diamine N,N'-diacetic acid hydrazinonicotinamide-conjugated Tyr3-octreotide (99mTc EDDA/HYNIC-TOC) single photon emission tomography/computed tomography (SPECT/CT) imaging of somatostatin receptors is used in the assessment of neuroendocrine tumours (NETs). The objective of this study was to characterise quantitative standardised uptake value (SUV) SPECT/CT of normal physiological uptake and NET disease. Forty-four patients (22 female and 22 male) referred for 99mTc EDDA/HYNIC-TOC SPECT/CT imaging for diagnosis/primary staging (n = 28) or the assessment of residual/recurrent disease (n = 16) were included. SPECT/CT SUVmax values were determined for normal physiological uptake (spleen, kidney, liver and bone) and NET disease (liver metastases, metastatic lymph nodes, bone metastases and intrapulmonary lesions). Statistical testing was performed to compare normal uptake and NET disease uptake in liver and bone (Student's t-test). The highest normal physiological uptake was observed in the spleen (mean SUVmax 29.8, SD 13.7), with lower uptake in the kidneys (16.7, 3.2) and liver (7.3, 2.1). Increased SUVmax values were observed in primary tumour and metastatic disease, greatest in liver metastases (21.8, 13.3), with lower, similar values obtained for metastatic lymph nodes (16.3, 7.5) and intrapulmonary lesions (17.5, 16.8). SUVmax in bone metastases averaged 12.9 (7.0). Significant differences were observed between normal and metastatic SUVmax in the liver and bone (P < 0.01). SPECT/CT SUV quantification is feasible in a manner similar to PET/CT. 99mTc EDDA/HYNIC-TOC SPECT/CT SUVmax has been characterised in NET disease, demonstrating high target to non-target ratios for primary tumours and metastatic lesions.

Early Injection of Furosemide Increases Detection Rate of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT.

The aim of this study was twofold. First, we aimed to assess the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of 68Ga-PSMA-11 before it binds to the PSMA receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Methods: In a retrospective analysis, 2 different groups with 220 prostate cancer patients each, referred for 68Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients in group 1 (median prostate-specific antigen, 1.30 ng/mL) received no preparation before imaging, whereas patients in group 2 (median prostate-specific antigen, 0.82 ng/mL) were injected with 20 mg of furosemide and 500 mL of sodium chloride (NaCl 0.9%) immediately after tracer injection. The presence of local recurrence was assessed visually. In addition, the intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide than in patients without preparation: 56 cases (25.5%) versus 38 cases (17.3%), respectively (P = 0.048). Median maximum SUVs (SUVmax) of organs with physiologic uptake of 68Ga-PSMA-11 in groups 1 and 2 were urinary bladder (63.0 vs. 8.9), kidney (55.6 vs. 54.5), liver (9.9 vs. 9.4), spleen (11.2 vs. 11.9), small bowel (16.2 vs. 17.1), parotid gland (19.2 vs. 19.6), lacrimal gland (8.9 vs. 10.9), blood-pool activity (2.2 vs. 2.3), muscle (1.0 vs. 1.1), and bone (1.6 vs. 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg of furosemide at the time point of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-PSMA-11 PET/CT. As intensity of 68Ga-PSMA-11 uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of 68Ga-PSMA-11 seems unlikely.

Physiologically decreased F-18 fluorodeoxyglucose uptake in the lower vertebrae associated with daily drinking habit in Japanese men with alcohol flushing reaction.

Alcohol flushing reaction (AFR) is known as one of the risks for esophageal squamous cell cancer, and scientists have been elucidating this issue. However, little attention has been given to relevant imaging features. This study aims to investigate whether physiological 18F-fluorodeoxyglucose (FDG) uptake patterns in vertebrae are associated with drinking habits or AFR. Japanese male patients who underwent FDG positron emission computed tomography for evaluation of their known or suspected malignancies or inflammatory diseases were asked about their drinking habits and AFR. Altogether, 192 patients, 139 every-day drinkers and 53 non-drinkers were evaluated. Comparing the FDG uptake between that in the thoracic region and that in the lumbar region, vertebral uptake was visually classified into four patterns: Ld, dominant in lumbar region; TL, almost equal in both regions; BL, slightly higher in thoracic region (borderline pattern); Td, dominant in thoracic region. The uptake patterns were evaluated according to drinking habit (every-day drinker or non-drinker), AFR (flusher or non-flusher), and the combination of these two factors (habit/reaction: every-day drinker/flusher, every-day drinker/non-flusher, non-drinker/flusher, or non-drinker/non-flusher). There were 95 flushers (51 every-day drinkers and 44 non-drinkers) and 97 non-flushers (88 every-day drinkers and 9 non-drinkers). Ld, TL, BL, and Td patterns were observed in 0, 109 (56.8%), 31 (16.1%), and 52 (27.1%) patients, respectively. Td and BL patterns were more frequently observed in every-day drinkers compared with non-drinkers (p=0.0467). Though the uptake patterns did not differ between flushers and non-flushers (p=0.116), the Td pattern was more frequently observed in every-day drinkers/flushers (51%) compared with every-day drinkers/non-flushers (20.5%), non-drinkers/flushers (13.6%), and non-drinkers/non-flushers (22.2%) (p=0.0014). The Td pattern was observed in patients with various diseases, with higher frequency in esophageal cancer, head and neck cancer, and lung cancer compared with other diseases. In conclusion, drinking habits and AFR were related to the vertebral uptake pattern with decreased uptake in the lumbar region in Japanese male patients.

Biological Effect of Tetracycline Antibiotics on a Soil-Lettuce System and Its Migration Degradation Characteristics

Residual tetracycline antibiotics (TCs) in farmland soils with the application of livestock manure cause risks to the growth of vegetables and soil ecology. Here, pot experiments are carried out using through exogenous addition of different levels of oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC), to study the physiological toxicity, uptake, and transportation of TCs in lettuce. The subsequent degradation of TCs in soil was also evaluated along with analyses of soil enzyme activity and microbial population dynamics. The results showed that the biomass of lettuce decreased with application of TCs as well as the chlorophyll-a, chlorophyll-b, and carotenoid content. Consequently, net photosynthetic rates were inhibited, and SOD, POD, and CAT increased under the stress imposed by the TCs. With an increase in the level of TC application, uptake by lettuce plants increased while the bioconcentration and translocation factors decreased. When OTC, TC, and CTC in the soil were below 150 mg·kg-1, the health risk from the edible parts of lettuce was low (HQ<0.1). The TC degradation rate in different soils was ranked in the order of control soil > rhizosphere soil > bulk soil. The OTC degradation rates in the soils were significantly lower than for TC and CTC. TCs (150-1350 mg·kg-1) significantly inhibited urease and rhizosphere catalase activity in soil and reduced the number of soil culturable bacteria and fungi.

18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging review of benign lesions of the thorax.

2-deoxy-2-(Fluorine-18) fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been used exclusively to diagnose malignancies. However, increased 18F-FDG uptake is not always limited to malignant lesions. This imaging review demonstrates the physiological 18F-FDG uptake of normal structures in the thorax and illustrates many benign pathological lesions with standardized uptake value >2.5. These various conditions can be broadly categorized into three groups: infective lesions, active granulomatous diseases such as sarcoidosis, noninfectious/inflammatory, or proliferative conditions such as radiation pneumonitis, postlung transplant lymphoproliferative disorders, occupational pleuropulmonary complications, and postsurgical conditions, all of which can demonstrate varying degrees of 18F-FDG uptake on PET/CT based upon the degree of inflammatory activity. Familiarity of false-positive findings improves the PET/CT evaluation accuracy of benign lesions of the thorax. Radiation exposure and surgical history correlation along with imaging cross check evaluation of radiographs and magnetic resonance images for the anatomic location remains the mainstay of PET/CT characterization of positive findings.

PET/computed tomography enterography.

Interpretation of gastrointestinal PET/computed tomography (PET/CT) is often complicated by anatomy including bowel folds, flexures, variant redundancy, decompressed bowel segments and physiological uptake. This makes it very difficult to identify both true positives and true negatives, compromising both sensitivity and specificity. CT enterography is increasingly being integrated into the field of nuclear medicine to address these issues. This technique uses the combination of negative/neutral contrast to distend the lumen of the gut and iodinated contrast to enhance the gastrointestinal wall and pathological findings. Apart from augmentation in the diagnostic performance, the technique also improves the quality of the imaging, confidence of the reporting physician and inter-rater agreement. Therefore, this technique has found favor among nuclear medicine physicians, in the imaging of chronic inflammatory disorders and malignancies in and of the gut. It is a feasible and easily executable procedure with minimal and manageable side-effects and should be routinely recommended in cases where interference from physiologic findings is expected.

Pre-coating of protein modulate patterns of corona formation, physiological stability and cytotoxicity of silver nanoparticles

Surface functionalization on silver nanoparticles greatly affects the dynamics of protein corona formation. In the present study, the implications of protein pre-coating on corona formation and nanoparticle's physiological stability, cellular uptake and toxicity were studied on similar sized alkaline protease coated nanoparticles of biological and chemical origin along with the uncoated nanoparticle as compared to the albumin coated nanoparticles. All four nanoparticle types invited serum protein adsorption on their surface. However, the presence of protein pre-coating on nanoparticle surface significantly reduced the extent of further protein binding. Moreover, corona formation on pristine nanoparticles significantly improved their stability in the biological medium. The effect was found to be diluted in protein pre-coated nanoparticles with due exception. Results obtained in the cell-based experiment suggested that the nanoparticles binding to the cell, its uptake, and toxicity in different cell lines can be directly linked to their physiological stability owing to corona formation.

PET/CT in Multiple Myeloma: Beyond FDG.

Recent advances in the diagnosis and treatment of multiple myeloma (MM) have highlighted the importance of imaging methods, not only in the localization and extent of the disease but also in prognostic stratification and assessment of response to therapy. In this context, PET/CT, combining both morphological and functional information, is particularly useful in this pathology. The tracer mostly used is 18F-FDG, a glucose analog, which provides extremely accurate information with a sensitivity ranging from 80 to 100%. However, this tracer has some limitations, mostly related to the physiological uptake of FDG in the bone marrow and brain, which reduce its effectiveness. For this reason, some studies in the literature have evaluated the effectiveness of other PET tracers, which provide information on protein metabolism or the synthesis of metabolic plasma membranes, such as choline and methionine, as well as innovative radiopharmaceuticals, directed against receptors expressed by cells of myeloma, including tracers directed to the chemokine receptor. This review analyzes the characteristics and accuracy of non-FDG tracers in the management of patients with multiple myeloma.

Epidemiology and (Patho)Physiology of Folic Acid Supplement Use in Obese Women before and during Pregnancy.

Preconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status, lifestyle, and medical conditions.

Somatostatin receptor-positive breast lesions on 68Ga-DOTATATE PET/CT.

This study sets out to evaluate patients with increased uptake in breast lesions on 68Ga-DOTATATE PET/CT (DOTA PET) and determine the clinical significance of somatostatin receptor (SSTR) positive breast lesions. We retrospectively evaluated all patients with increased SSTR uptake in breast lesions on DOTA PET. Patients with physiological (e.g., lactation) or normal variant breast uptake (e.g., mild diffuse glandular uptake) were excluded. The maximum standard uptake value (SUVmax) was calculated using a manually drawn region of interest in the most intense uptake of breast lesions. All lesions were correlated with breast imaging, including mammography and ultrasonography. Histopathological correlation was performed if the lesion was suspicious for malignancy. Lesions were followed up radiologically (1-8years). Out of 1573 retrospectively analyzed DOTA PET scans, the incidence of SSTR + breast lesions was measured as 1.1% (n = 18); however, 4 of 18 patients were excluded due to the lack of final diagnosis of lesions. The median age was 35 (range 14-58years), and all patients were female. The median SUVmax of SSTR + breast lesions was 5.2 (range 1.5-12.6) for a total of 14 patients. Twelve patients had a single SSTR + breast lesion, while 2 patients had multiple SSTR + lesions on bilateral breasts. In 6 patients, single SSTR + lesions were considered as fibroadenoma; in 2 patients, multiple SSTR + lesions were considered as metastases of NET, based on correlative breast imaging. In 6 patients, histopathological confirmation was needed for the final diagnosis. Histopathologic findings confirmed fibroadenoma in 4 patients by biopsy, in 1 patient with surgical removal of the lesion. The last patient who had a history of IDC was diagnosed with a recurrence of IDC with biopsy. The median SUVmax was 5.1 (range 1.5-9.4) for malignant breast lesions and 5.4 (range 2.2-12.6) for benign breast lesions. SSTR + breast lesions on DOTA PET are rarely seen in clinical practice. Uptakes of breast lesions in our cases were variable and not useful for differential diagnosis of lesions. It seems that SSTR + breast lesions should be evaluated with clinical and radiological characteristics, and correlative breast imaging and/or histopathological verification should be performed for suspicious lesions to avoid misdiagnosis.

Associations of physiologic myocardial 18F-FDG uptake with fasting duration, HbA1c, and regular exercise.

The variability of physiologic 18F-FDG uptake in the myocardium has hampered the accurate evaluation of cardiac glucose metabolism. We investigated the effects of multiple factors, including fasting duration and physical activity, on the physiologic uptake of 18F-FDG by the myocardium in healthy participants. A total of 446 participants (predominantly male, 91%) in a health screening program were included in this retrospective study. For the visual analysis of myocardial 18F-FDG uptake, the participants were categorized into three groups according to qualitative visual scales (QVS). For the quantitative analysis, the maximum SUV of the left ventricular myocardium was measured. Significant differences were observed in fasting duration (p < 0.001), SUVmax (p < 0.001), aspartate aminotransferase (AST) (p < 0.001), alanine aminotransferase (ALT) (p < 0.001), gamma-glutamyl transpeptidase (γ-GTP) (p = 0.001), and uric acid (p = 0.015) among the QVS groups. Participants who regularly exercised with vigorous activity (p = 0.032) and HbA1c > 6% (p = 0.005) showed significant association with myocardial FDG uptake in the Chi-squared test. The median value of fasting duration decreased significantly as the QVS of the myocardium increased. Twenty-nine of the 31 participants (93.5%) who fasted for 21.5h or more showed a suppressed FDG uptake (mean SUVmax = 2.1). In multivariate logistic regression analysis, fasting duration (OR = 0.74, 95% CI 0.69-0.80, p < 0.001), HbA1c > 6% (OR = 0.29, 95% CI: 0.12 - 0.66, p = 0.004), uric acid (OR = 0.82, 95% CI 0.68-1.00, p = 0.049) and regular exercise with vigorous activity (OR = 1.75, 95% CI 1.13-2.70, p = 0.012) were significant factors for physiologic myocardial FDG uptake. Reduced physiologic 18F-FDG uptake of the myocardium was associated with longer fasting duration, higher level of HbA1c, and less frequency of regular exercise with vigorous activity. For the preparation of cardiac 18F-FDG PET, inclusion of longer fasting duration (more than 18h) might be necessary for the adequate suppression of physiologic 18F-FDG myocardial uptake.

A reduced physiological 18F-fluorodeoxyglucose uptake in the brain and liver caused by malignant lymphoma being deprived of the tracer.

Purpose : To investigate whether or not the physiological brain and liver FDG uptake are decreased in patients with highly accelerated glycolysis lesions. Methods : We retrospectively analyzed 51 patients with malignant lymphoma. We compared the FDG uptake in the brain and liver of the patients with that in a control group. In 24 patients with a complete response (CR) or partial response (PR) to treatment, we compared the brain and liver uptake before and after treatment. Results : The maximum standardized uptake value (SUVmax) and total glycolytic volume (TGV) of the brain as well as the SUVmax and mean standardized uptake value (SUVmean) of the liver in malignant lymphoma patients were 13.1 ± 2.3, 7386.3 ± 1918.4, 3.2 ± 0.5, and 2.3 ± 0.4, respectively ; in the control group, these values were 14.9 ± 2.4, 8566.2 ± 1659.5, 3.4 ± 0.4, and 2.5 ± 0.3, respectively. The SUVmax and TGV of the brain and the SUVmean of the liver in malignant lymphoma patients were significantly lower than the control group. The SUVmax and TGV of the brain after treatment were significantly higher than before treatment. Both the SUVmax and SUVmean of liver after treatment were higher than before treatment, but not significant. Conclusion : A decreased physiological brain and liver FDG uptake is caused by highly accelerated lesion glycolysis. J. Med. Invest. 68 : 181-185, February, 2021.

Physiological FDG uptake in growth plate on pediatric PET.

18F-Fluorodeoxyglucose (FDG) uptake in children is different from that in adults. Physiological accumulation is known to occur in growth plates, but the pattern of distribution has not been fully investigated. Our aim was to evaluate the metabolic activity of growth plates according to age and location. We retrospectively evaluated 89 PET/CT scans in 63 pediatric patients (male : female=25 : 38, range, 0-18 years). Patients were classified into four age groups (Group A: 0-2 years, Group B: 3-9 years, Group C: 10-14 years and Group D: 15-18 years). The maximum standardized uptake value (SUVmax) of the proximal and distal growth plates of the humerus, the forearm bones and the femur were measured. The SUVmax of each site and each age group were compared and statistically analyzed. We also examined the correlations between age and SUVmax. As for the comparison of SUVmax in each location, the SUVmax was significantly higher in the distal femur than those in the other sites (p< 0.01). SUVmax in the distal humerus and the proximal forearm bones were significantly lower than those in the other sites (p< 0.01). In the distal femur, there was large variation in SUVmax, while in the distal humerus and the proximal forearm bones, there was small variation. As for the comparison of SUVmax in each age group, the SUVmax in group D tended to be lower than those in the other groups, but in the distal femur, there was no significant difference among each age group. Our data indicate that FDG uptake in growth plates varies depending on the site and age with remarkable uptake especially in the distal femur.

Biodistribution and Radiation Dosimetric Analysis of [68Ga]Ga-RM2: A Potent GRPR Antagonist in Prostate Carcinoma Patients

[68Ga]Ga-RM2 is a promising innovative positron emission tomography (PET) tracer for patients with primary or metastatic prostate carcinoma. This study aims to analyze the biodistribution and radiation dosimetry of [68Ga]Ga-RM2 in five prostate cancer patients. The percentages of injected activity in the source organs and blood samples were determined. Bone marrow residence time was calculated using an indirect blood-based method. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) was used to determine residence times, organ absorbed and effective doses. Physiological uptake was seen in kidneys, urinary bladder, pancreas, stomach, spleen and liver. Blood clearance was fast and followed by rapid clearance of activity from kidneys resulting in high activity concentrations in the urinary bladder. The urinary bladder wall was the most irradiated organ with highest mean organ absorbed dose (0.470 mSv/MBq) followed by pancreas (0.124 mSv/MBq), stomach wall (0.063 mSv/MBq), kidneys (0.049 mSv/MBq) and red marrow (0.010 mSv/MBq). The effective dose was found to be 0.038 mSv/MBq. Organ absorbed doses were found to be comparable to other gallium-68 labelled GRPR antagonists and lower than [68Ga]Ga-PSMA with the exception of the urinary bladder, pancreas and stomach wall. Remarkable interindividual differences were observed for the organ absorbed doses. Therefore, [68Ga]Ga-RM2 is a safe diagnostic agent with a significantly lower kidney dose but higher pancreas and urinary bladder doses as compared to [68Ga]Ga-PSMA.

Physiologic prostate-specific membrane antigen-targeted 18F-DCFPyL uptake in the epididymis head newly appreciated on digital PET/CT.

The published physiological distribution of prostate specific membrane antigen (PSMA) PET ligands includes normal uptake in the lacrimal glands, salivary glands, bowel, liver, spleen, kidneys and parasympathetic ganglia but does not include the epididymis. Retrospective review of 134 PSMA-targeted 2-(3-(1-carboxy-5-[(6-[18F]fluoropyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid (18F-DCFPyL) PET/CT scans performed on a latest generation digital scanner for radiotracer uptake in the epididymal head region was correlated with multiple clinical and laboratory factors. Physiologic PSMA radiotracer uptake in the epididymal head region was present in 57% of all subjects, including 29% in those with a total serum testosterone ≤ 5 nmol/L and 65% of patients with serum testosterone > 5 nmol/L, odds ratio of 0.21 (P < 0.01). Epididymal head uptake is physiologic and very common on digital PSMA PET/CT and is more frequent in patients with higher serum testosterone levels. The enhanced small structure detection of digital PET/CT is the most likely explanation for the novel visualization of this normal variant.

Development of Combination Methods for Detecting Malignant Uptakes Based on Physiological Uptake Detection Using Object Detection With PET-CT MIP Images.

Deep learning technology is now used for medical imaging. YOLOv2 is an object detection model using deep learning. Here, we applied YOLOv2 to FDG-PET images to detect the physiological uptake on the images. We also investigated the detection precision of abnormal uptake by a combined technique with YOLOv2. Using 3,500 maximum intensity projection (MIP) images of 500 cases of whole-body FDG-PET examinations, we manually drew rectangular regions of interest with the size of each physiological uptake to create a dataset. Using YOLOv2, we performed image training as transfer learning by initial weight. We evaluated YOLOv2's physiological uptake detection by determining the intersection over union (IoU), average precision (AP), mean average precision (mAP), and frames per second (FPS). We also developed a combination method for detecting abnormal uptake by subtracting the YOLOv2-detected physiological uptake. We calculated the coverage rate, false-positive rate, and false-negative rate by comparing the combination method-generated color map with the abnormal findings identified by experienced radiologists. The APs for physiological uptakes were: brain, 0.993; liver, 0.913; and bladder, 0.879. The mAP was 0.831 for all classes with the IoU threshold value 0.5. Each subset's average FPS was 31.60 ± 4.66. The combination method's coverage rate, false-positive rate, and false-negative rate for detecting abnormal uptake were 0.9205 ± 0.0312, 0.3704 ± 0.0213, and 0.1000 ± 0.0774, respectively. The physiological uptake of FDG-PET on MIP images was quickly and precisely detected using YOLOv2. The combination method, which can be utilized the characteristics of the detector by YOLOv2, detected the radiologist-identified abnormalities with a high coverage rate. The detectability and fast response would thus be useful as a diagnostic tool.

Effect of fasting duration on myocardial fluorodeoxyglucose uptake in diabetic and nondiabetic patients.

To detect cardiac hypermetabolic lesions using fluorodeoxyglucose (FDG) with PET/computed tomography (PET/CT), the efficiency of long fasting and temperature condition for lowering physiological myocardial FDG uptake is controversial and may be confounded by other factors. We thus aimed to investigate the impact of fasting duration and ambient temperature on myocardial uptake in diabetic and nondiabetic patients. FDG PET/CT scans (n = 666) were reviewed and the myocardial uptake was visually graded on a four-point scale and quantified using standardized uptake value (SUV). The associations between myocardial uptake and fasting duration, diabetes status, ambient temperature parameters, age, gender, and BMI were evaluated. Intraobserver [κ = 0.94; intraclass correlation coefficient (ICC) = 0.99] and interobserver (κ = 0.91; ICC = 0.99) reliabilities of both visual and SUV measurements were all excellent. Fasting duration and diabetes status were found to be significantly associated with myocardial FDG uptake, but the ambient temperature parameters and other factor were not. Patients with intense (Grade 4) myocardial uptake had a shorter fasting duration (P = 0.011). The SUVmax of myocardium was significantly higher in nondiabetic than diabetic patients (P < 0.001). Fasting duration ≥ 12 h in diabetic and ≥16 h in nondiabetic patients was associated with low prevalence of Grade 4 uptake (4.2%, P = 0.016; 2.3%, P = 0.028). Fasting for long enough durations but not ambient temperature was associated with decreased physiological myocardial FDG uptake. A fasting duration of more than 12 h for diabetic, 16 h for nondiabetic patients is a simple and valuable recommendation.

Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.