Glandular Uptake Research Articles

Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

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.

PET/CT analysis of 21 patients with breast cancer: physiological distribution of 18F-choline and diagnostic pitfalls.

Objectives18F-choline is a useful tracer for detecting tumours with high lipogenesis. Knowledge of its biodistribution pattern is essential to recognise physiological variants. The aim of this study was to describe the physiologic distribution of 18F-choline and pitfalls in patients with breast cancer.MethodsTwenty-one consecutive patients with breast cancer (10 premenopausal and 11 postmenopausal women; mean age, 52.82 ± 10.71 years) underwent 18F-choline positron emission tomography (PET)/computed tomography (CT) for staging. Whole-body PET/CT was acquired after 40 minutes of 18F-choline uptake. Acquired PET images were measured semiquantitatively.ResultsAll patients showed pitfalls unrelated to breast cancer. These findings were predominantly caused by physiological glandular uptake in the liver, spleen, pancreas, bowels, axial skeleton (85%-100%), inflammation and benign changes (4.76%), appendicular skeleton (4.76%–19.049%), and site contamination (61.9%). In <1%, a concomitant metastatic neoplasm was found. The breast showed higher physiological uptake in premenopausal compared with postmenopausal woman (18F-choline maximum standardised uptake values [g/dL] of the right breast = 2.04 ± 0.404 vs 1.59 ± 0.97 and left breast = 2.00 ± 0.56 vs 1.93 ± 1.28, respectively).Conclusion18F-choline uptake was higher in premenopausal women. Physiological 18F-choline uptake was observed in many sites, representing possible pathologies.

Androgen Deficiency and Defective Intracrine Processing of Dehydroepiandrosterone in Salivary Glands in Sjögren’s Syndrome

.We hypothesized that in addition to dehydroepiandrosterone (DHEA) depletion, Sjögren's syndrome (SS) is characterized by local androgen deficiency in salivary glands and defects in local processing of DHEA. Sex steroid levels in serum and saliva were measured using enzyme immunoassays. Androgen effects on salivary gland cells were analyzed using the cysteine-rich secretory protein-3 (CRISP-3) androgen biomarker. Serum and salivary concentrations of androgens were low in SS. Substrate to end-product ratios and correlations suggest that in SS salivary glands DHEA is effectively converted to testosterone, but that there are defects in converting testosterone further to dihydrotestosterone (DHT). In healthy controls no such phenomenon was seen, but testosterone is effectively converted to DHT. Salivary glands contained type I 5-alpha-reductase, and its inhibition with dutasteride completely blocked the upregulating effect of DHEA, but not of DHT, on CRISP-3 in human salivary gland acinar cells. DHEA and DHT upregulate CRISP-3, which is reportedly low in SS. The effect of DHEA on CRISP-3 is indirect and is inhibited by dutasteride, showing that there is intracrine processing of DHEA in salivary glands. In healthy glands, but not in SS, DHEA is effectively taken up and converted to DHT. Sex steroid concentrations in saliva in part reflect glandular uptake of DHEA-sulfate and local intracrine DHEA metabolism, which seem to be defective in SS. Our study demonstrates a prominent androgen deficiency and a defect in intracrine production of active androgens in SS salivary glands, also suggesting that salivary DHT cannot be maintained at a normal level in this female-dominant autoimmune exocrinopathy.

Pathways for Nutrient Transport in the Pitchers of the Carnivorous Plant Nepenthes alata

Glands of the carnivorous pitcher plant Nepenthesalata are active in transport of materials into and out of the pitcher lumen, indicating dual functions in both secretion and absorption. This study examined the potential for open transport through these glands using the ultrastructural tracer lanthanum, which is restricted to the apoplast, and the fluorescent symplastic tracer, 6(5)carboxyfluorescein. Glandular uptake of lanthanum from the pitcher fluid occurred through the outer cell wall between irregularly spaced cutinized deposits, but was blocked from entering the underlying mesophyll cell walls by thick endodermal-like regions. Similarly, lanthanum localization showed an open apoplastic pathway from the petiole to the endodermal regions in the gland base. Thus, transport of materials into or out of the gland must occur through the symplast. 6(5)Carboxyfluorescein showed that these glands transport fluids directly from the pitcher fluid into vascular endings immediately beneath them via a symplastic route. When applied to the petiolar vascular system, the fluorescent tracer freely entered immature pitchers, but was blocked from entering the lumen of the mature pitcher by an endodermal zone. An ultrastructural survey showed infrequent pits with plasmodesmatal connections to adjoining subepidermal cells. These results indicate that the function of the gland is developmentally regulated. Prior to maturity, the primary function of the gland appears to be secretion. However, at maturity, secretion is blocked by an endodermal layer, which limits the function of the gland to absorption. These studies support the theory that the glands of Nepenthesalata are specialized for the bi-directional transport of materials.

Scintigraphic assessment of salivary function and excretion response in radiation-induced injury of the major salivary glands.

Both loss of the secretory function and impairment of the excretion may play a role in radiation-induced injury of the major salivary glands after radiotherapy for head and neck malignancies. Therefore, quantitative 99mTc-pertechnetate (99mTc) salivary scintigraphy to assess trapping, secretion, and excretion, was used to analyze irradiation-induced changes in relation to the radiation dose and the time interval after radiotherapy. Salivary scintigraphy was performed on 25 patients who had been irradiated to the neck and head for various malignancies with irradiation of the major salivary glands and in 6 nonirradiated patients. Excretion was induced by stimulation with carbachol (Carbacholum, Pharmachemie BV, Haarlem, The Netherlands). As a parameter for salivary glandular trapping and secretion, the cumulative 99mTc-pertechnetate glandular uptake in the first 12 minutes was used. Scintigraphic data were analyzed for each patient and for each individual gland at three radiation dose levels (range, 5-70 Gy), and at short (range, 2-7 months) and long (range, 10-50 months) intervals after radiotherapy. The excretion response to the stimulant carbachol was totally or partially disturbed in 84% of the irradiated patients. For individual glands, excretion was maintained in all glands irradiated with 25 Gy or less, in nearly half of the glands at doses of 25-45 Gy, and was almost invariably impaired at doses higher than 45 Gy, regardless of the time interval after radiotherapy. Although cumulative 99mTc glandular uptake tended to decrease at higher radiation dose levels (z = -3.059, P < 0.0022), at 45 Gy or more, cumulative 99mTc uptake was considerably higher in glands examined at a short postirradiation interval compared with glands examined after a long time interval (P = 0.0001). This tendency, seen for both parotid and submandibular glands, was not observed at doses lower than 45 Gy. These data suggest that in the first period after high dose irradiation, xerostomia is based predominantly on the failure of the gland to excrete saliva, whereas in the later period, a decreased trapping ability together with loss of secretory function play an additional role. Salivary scintigraphy using 99mTc-pertechnetate is a suitable method to assess radiation-induced salivary gland injury. The test is able to detect salivary glandular dysfunction in an early phase and may be useful to predict which patients will respond symptomatically to salivary stimulants.

Effects of ClO 2 on the absorption and distribution of dietary iodide in the rat

Aqueous chlorine dioxide (ClO 2), an alternative disinfectant for drinking water, was found to decrease gastrointestinal (GI) bioavailability of dietary iodide. It has been previously reported that subchronic exposure to ClO 2 decreases thyroxine (T 4) levels in nonhuman primates. In this study in vitro experiments with animal feed, isolated rat stomachs, as well as in vivo studies with intact rats, showed that ClO 2 in drinking water (at in situ concentrations as low as 2 ppm) oxidizes iodide to its reactive elemental (radical) state, binding it to organic substances present in the GI tract. A single instance of acute exposure to ClO 2, however, did not decrease blood iodide levels, or thyroid glandular uptake of iodine.

The effect of luteineizing hormone on chicken testis and pineal gland uptake of 32P.

The glandular uptake of radioactive phosphorus (32P), administered carrier-free, was used as an endpoint for the study of the effects of luteinizing hormone (LH) on the testis and pineal gland of 3-, 10- and 13-day-old White Leghorn cockerels. Pineal uptake of 32P of the 13-day-old birds decreased and testis uptake of 32P increased following LH treatment. Maximum effects were observed when 20 mug LH was administered 4.0 h before autopsy. Although testis uptake of 32P increased following LH treatment in 3- and 10-day-old cockerels, pineal uptake of 32P remained unchanged.

Pyridine nucleotides in the thyroid gland. II. Effect of nicotinamide, nicotinic acid and L-tryptophan administration.

The concentration of pyridine nucleotides in thyroid glands of rats given nicotinamide (NAm), nicotinic acid (NAc) or L-tryptophan (L-T) was measured. NAm, NAc and L-T given 4 and 24 hr before thyroidectomy substantially increased thyroid NAD and NADH, while NADP and NADPH were unchanged. The most potent agent was NAm; thyroid NAD concentration remained high for at least 24 hr after a single injection. TSH by acute injection (3 hr) and 6-n-PTU added to diet for 10 days further enhanced the increase in NAD induced by NAm, but not that by NAc or L-T. Hypophysectomy and puromycin injection diminished, while actinomycin did not prevent the NAm-induced increase in NAD and NADH. NAm injection did not affect glandular uptake or release of 131I nor organification of 131I in vivo or by homogenates. Thyroid ATP concentration and oxidation of glucose-U-14CO2 were unaffected by NAm injection. Glandular NAD does not appear to be rate limiting for NADP formation nor does its presence in high concentrations affect the m...

Early enhancement by thyrotropin of thyroid organification of circulating iodide.

The early effect of TSH upon thyroid uptake and organification of various doses of iodide was studied by giving 131Ilabeled iodide of known specific activity as a single injection to Purina-fed rats, followed by TSH or saline intravenously. Three hr later thyroid concentration and proportion of PB131I and iodide-131I were determined by paper chromatography and glandular content of newly formed PB127I calculated from the specific activity of the iodide given. At the 5 ng iodide dose, glandular uptake and PB127I concentration were the same in TSH and control groups. When 50-5000 αg of iodide was given, TSH enhanced glandular uptake and PB127I formation. The increment in PBI included both iodotyrosines and iodothyronines and was not abolished by perchlorate. At the higher iodide doses, PBI formation was severely depressed in controls (Wolff-Chaikoff effect) but was unimpaired in the TSH group. The results suggest that, under these conditions, TSH promptly stimulates uptake and organification of circulating i...