Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

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Relationship of amyloid-β1–42 in blood and brain amyloid: Ginkgo Evaluation of Memory Study

Brain Communications ◽

10.1093/braincomms/fcz038 ◽

2019 ◽

Vol 2 (1) ◽

Cited By ~ 1

Author(s):

Oscar L Lopez ◽

William E Klunk ◽

Chester A Mathis ◽

Beth E Snitz ◽

Yuefang Chang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Pet Imaging ◽

Standardized Uptake Value ◽

Amyloid Plaques ◽

Amyloid Deposition ◽

Pittsburgh Compound B ◽

Blood Samples ◽

Apolipoprotein E4 ◽

The Brain ◽

Brain Amyloid Deposition

Abstract A blood test that predicts the extent of amyloid plaques in the brain and risk of Alzheimer’s disease would have important benefits for the early identification of higher risk of dementia and Alzheimer’s disease and the evaluation of new preventative therapies. The goal of this study was to determine whether plasma levels of amyloid-β1–42, 1–40 and the amyloid-β1–42/1–40 ratio among participants in the Pittsburgh centre of the Ginkgo Evaluation of Memory Study were related to the extent of brain fibrillar amyloid plaques measured in 2009 using Pittsburgh compound-B PET imaging, hippocampal volume, cortical thickness in the temporal lobe and white matter lesions. There were 194 participants who had Pittsburgh compound-B measurements in 2009 with the mean age of 85 years; 96% were white and 60% men. Pittsburgh compound-B positivity was defined as a standardized uptake value ratio of ≥1.57. Amyloid-β in blood was measured using a sandwich enzyme-linked immunosorbent assay developed by Eli Lilly and modified at the University of Vermont. All participants were nondemented as of 2008 at the time of study close out. The study sample included 160 with blood samples drawn in 2000–02 and 133 from 2009 and also had brain amyloid measured in 2009. All blood samples were analysed at the same time in 2009. Plasma amyloid-β1–42 was inversely related to the percent Pittsburgh compound-B positive (standardized uptake value ratio ≥1.57), β −0.04, P = 0.005. Practically all participants who were apolipoprotein-E4 positive at older ages were also Pittsburgh compound-B positive for fibrillar amyloid. Among apolipoprotein-E4-negative participants, quartiles of amyloid-β1–42 were inversely related to Pittsburgh compound-B positivity. In multiple regression models, plasma amyloid-β1–42 measured in 2000–02 or 2009 were significantly and inversely related to Pittsburgh compound-B positivity as was the amyloid-β1–42/1–40 ratio. There was a 4-fold increase in the odds ratio for the presence of Pittsburgh compound-B positivity in the brain in 2009 for the first quartile of amyloid-β1–42 as compared with the fourth quartile in the multiple logistic model. This is one of the first longitudinal studies to evaluate the relationship between amyloid-β1–42 in the blood and the extent of brain amyloid deposition measured by PET imaging using Pittsburgh compound-B. Our findings showed that remote and recent low plasma amyloid-β1–42 levels were inversely associated with brain amyloid deposition in cognitively normal individuals. However, changes in plasma amyloid-β1–42 over time (8 years) were small and not related to the amount of Pittsburgh compound-B.

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Consumption of Cross-Linked Resistant Starch (RS4XL) on Glucose and Insulin Responses in Humans

Journal of Nutrition and Metabolism ◽

10.1155/2010/651063 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 35

Author(s):

Enas K. Al-Tamimi ◽

Paul A. Seib ◽

Brian S. Snyder ◽

Mark D. Haub

Keyword(s):

Dietary Fiber ◽

Resistant Starch ◽

Area Under The Curve ◽

Postprandial Glucose ◽

Wheat Starch ◽

Blood Samples ◽

Serial Blood ◽

Insulin Levels ◽

Insulin Responses ◽

First Time

Objective. The objective was to compare the postprandial glycemic and insulinemic responses to nutrition bars containing either cross-linked RS type 4 (RS4XL) or standard wheat starch in normoglycemic adults (n= 13; age = 27±5 years; BMI = 25±3 kg/m2).Methods. Volunteers completed three trials during which they consumed a glucose beverage (GLU), a puffed wheat control bar (PWB), and a bar containing cross-linked RS4 (RS4XL) matched for available carbohydrate content. Serial blood samples were collected over two hours and glucose and insulin concentrations were determined and the incremental area under the curve (iAUC) was calculated.Results. TheRS4XLpeak glucose and insulin concentrations were lower than the GLU and PWB (P<.05). The iAUC for glucose and insulin were lower following ingestion of RS4 compared with the GLU and PWB trials.Conclusions. These data illustrate, for the first time, that directly substituting standard starch withRS4XL, while matched for available carbohydrates, attenuated postprandial glucose and insulin levels in humans. It remains to be determined whether this response was due to the dietary fiber and/or resistant starch aspects of theRS4XLbar.

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Photoacoustic detection of circulating melanoma cells as a predictor of metastasis in stage III patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e21053 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e21053-e21053

Author(s):

John Andrew Viator ◽

Martin Sanders ◽

Ahmad A. Tarhini ◽

Cindy Sander ◽

Robert Hugh Edgar ◽

...

Keyword(s):

Laser Light ◽

Melanoma Cells ◽

Ultrasonic Waves ◽

Flow Cytometer ◽

Disease State ◽

Stage Iii ◽

Blood Samples ◽

Serial Blood ◽

Melanoma Patients ◽

Stage Iii Melanoma

e21053 Background: Circulating tumor cells have been correlated with disease state and distant metastatic spread in cancer patients. We postulated that enumerating circulating melanoma cells (CMCs) may predict the onset of distant metastasis in Stage III patients. We detected CMCs using our photoacoustic flow cytometer, in which we irradiated enriched blood samples with nanosecond pulsed laser light. While there is no effect on non-optically active leukocytes, absorption of laser light by pigmented melanoma cells resulted in robust ultrasonic waves that indicated CMCs in the sample. Methods: We tested 32 archived samples from 9 Stage III melanoma patients using our photoacoustic flow cytometer. Each patient had between 2 and 6 serial blood samples. We used a pulsed Nd:YAG laser to irradiate mononuclear cells in suspension and under flow. The number of CMCs detected after testing was recorded, indicating the time sequence of circulating tumor cell activity. Results: The numbers of CTCs for each sample is shown in the table below. The ultimate disease state, whether the patient became metastatic or not, was blinded to the investigators who performed the photoacoustic tests. One sample for patient 3 indicated 63 CMCs, though this test was known to be contaminated and had an unknown number of false detections. Conclusions: We found that patients who had a series of more than 4 CMCs were more likely to become metastatic than those patients who tested for 4 CMCs for fewer, indicating that a sequence of CMC detections in serial blood draws provides a potentially strong predictor of metastasis in Stage III melanoma patients warranting further investigation at this and lower stages of melanoma. We are developing a more rigorous model based on time series analysis of CMCs for prediction of metastasis. [Table: see text]

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A study of the luteolytic mechanism of the antiprogesterone RU486 during the late-luteal phase in pseudopregnant rats

Journal of Endocrinology ◽

10.1677/joe.0.1500093 ◽

1996 ◽

Vol 150 (1) ◽

pp. 93-98 ◽

Cited By ~ 1

Author(s):

Y Nakamura ◽

H Tamura ◽

M Ono ◽

K Shimamura ◽

N Sugino ◽

...

Keyword(s):

Subcutaneous Injection ◽

Luteal Phase ◽

Treated Group ◽

Sesame Oil ◽

Serum Prolactin ◽

Control Group ◽

Serum Progesterone ◽

Blood Samples ◽

Serial Blood ◽

Late Luteal Phase

Abstract The purpose of this study was to examine the possible mechanism through which RU486 induces luteolysis during the late-luteal phase in pseudopregnant (PSP) rats. PSP rats received a subcutaneous injection of RU486 in sesame oil (5 mg/kg body weight) or sesame oil alone once a day between day 9 and day 11 of pseudopregnancy. Serial blood samples were collected on days 5, 9, 10, 11 and 12 and assayed for progesterone content. To examine the possible action of RU486 through a uterine and/or a pituitary (prolactin-dependent) mechanism, PSP rats and chronic hysterectomized PSP rats which had been hysterectomized before PSP induction received a subcutaneous injection of RU486 in sesame oil (5 mg/kg body weight), sesame oil alone, prolactin in 50% polyvinylpyrrolidone (15 IU/day), or RU486 and prolactin once a day between day 9 and day 11 of pseudopregnancy. Serial blood samples were collected on days 5, 9, 10 and 11 and assayed for progesterone content. Blood samples were also collected at 0400 h on day 12 and used for prolactin and progesterone determinations. To examine the direct effect of RU486 on corpus luteum and/or pituitary, hysterectomized rats underwent hypophysectomy and pituitary autotransplantation on dioestrus 1 and received a subcutaneous injection of RU486 in sesame oil or sesame oil alone for 3 days between day 21 and day 23 after surgery. Serial blood samples were collected on days 10, 21, 22, 23 and 24 and assayed for progesterone and prolactin contents. In ordinary PSP rats, serum progesterone levels were significantly (P<0·01) lower in the RU486-treated group than in the control group (9 ± 1 vs 53 ± 7 ng/ml; mean ± s.e.m.) on day 11. Serum prolactin levels at 0400 h on day 12 of pseudopregnancy were significantly (P<0·05) lower in the RU486-treated group than in the control group (16 ±4 vs 154 ±44 ng/ml; mean ± s.e.m.). The concomitant prolactin treatment reversed the luteolytic effects of RU486 on day 11 of pseudopregnancy. In hysterectomized PSP rats, RU486 also suppressed serum prolactin levels, and the concomitant prolactin treatment again reversed the luteolytic effects of RU486. In hysterectomized rats which were hypophysectomized and pituitary autotransplanted, RU486 treatment did not induce any significant changes in serum progesterone and prolactin levels. These results indicated that RU486 induced luteolysis during the late-luteal phase in PSP rats by suppressing prolactin secretion via a hypothalamic mechanism. Journal of Endocrinology (1996) 150, 93–98

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PSXII-16 High and medium ADG on LH profile in early-weaned heifers

Journal of Animal Science ◽

10.1093/jas/skz258.838 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 423-423

Author(s):

Janaina S Biava ◽

Marcos V C Ferraz ◽

Evandro M Ferreira ◽

Daniel M Polizel ◽

Gabriela B Oliveira ◽

...

Keyword(s):

Factorial Design ◽

Precocious Puberty ◽

Juvenile Period ◽

Blood Samples ◽

Serial Blood ◽

Second Period

Abstract This study evaluated the effects of ADG on number of pulses, amplitude and concentration of LH in pre-pubertal early-weaned heifers. Twenty ½Angus x ½Nellore were weaned (86±3 d of age and 91±1 kg BW), and allocated in 2×2 factorial design. Heifers were submitted to high (H) and medium (M) ADG in two periods. The first period occurred from 3 to 7 mo and the second from 7 mo to puberty (HH, HM, MH and MM). Diets in the first (CP 19%, NDF 24% and TDN 79%) and second periods (CP 14%, NDF 24% and TDN 78 %) were the same for all treatments, but the amount was controlled to get the ADG. Weekly, heifers were weighed and puberty status assessed by US. Serial blood samples were collected every 15 min for 12h at 6.5, 9.5 and 11.5 mo of age. The data were evaluated using SAS. The ADG was higher in H than M group in the first period (0.99±0.06 kg vs. 0.51±0.04 kg). In the second period, the ADG was 0.81±0.03 (HH), 0.5±0.03 (HM), 1.0±0.04 (MH) and 0.68±0.03 (MM). At 6.5 mo of age, heifers in H had an increase in LH pulses (2.1±0.5) compared with M (0.7±0.5) (period x age interaction P = 0.04). There was no effect of treatments on LH pulses in other ages, and in amplitude of LH pulse. The LH concentration was higher in HH than HM, MH and MM at 9.5 mo (1.72 vs. 1.07, 1.46 and 1.25±0.2 ng/mL) and 11.5 mo of age (2.01 vs. 1.65, 1.48 and 1.53±0.2 ng/mL), respectively. Despite differences in LH patterns, HH heifers reached puberty at a similar age to HM and MH (12±0.2 mo), however MM heifers (14.4±0.4 mo) reached puberty later (P = 0.09). Increasing ADG on juvenile period increased LH pulses but did not induce precocious puberty.

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A restraint system for the common marmoset (Callithrix jacchus)

Laboratory Animals ◽

10.1258/002367788780864501 ◽

1988 ◽

Vol 22 (2) ◽

pp. 148-150 ◽

Cited By ~ 6

Author(s):

K. T. O'Byrne ◽

K. D. Morris

Keyword(s):

Common Marmoset ◽

Callithrix Jacchus ◽

Restraint System ◽

Blood Samples ◽

Serial Blood ◽

Electrophysiological Recordings ◽

The Common

A method for restraining the marmoset in a primate chair is described. The device is inexpensive to construct, is reliable, and the majority of animals can be habituated to its use. The chair has been used in neurobiological studies employing electrophysiological recordings, with or without concurrent collection of serial blood samples.

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Acute effects of GnRF-induced gonadotrophin secretion upon ovarian steroid secretion in the ferret

Acta Endocrinologica ◽

10.1530/acta.0.1110373 ◽

1986 ◽

Vol 111 (3) ◽

pp. 373-377

Author(s):

Christine Matson ◽

B. T. Donovan

Keyword(s):

Acetic Acid ◽

Plasma Concentration ◽

Steroid Hormones ◽

Acute Effects ◽

Ovarian Steroid ◽

Blood Samples ◽

Steroid Secretion ◽

Serial Blood ◽

Gonadotrophin Secretion ◽

Thyrotrophic Hormone

Abstract. The effects of an increase in endogenous gonadotrophin secretion on the production of oestradiol, progesterone, androstenedione and testosterone by the ovaries of anaesthetized anoestrous and oestrous ferrets were followed. Gonadotrophin secretion was enhanced by the injection of gonadotrophin releasing factor (GnRF), and serial blood samples were collected over 9 h for hormone assay. Thyrotrophic hormone releasing factor (TRF) or acetic acid were injected for control purposes. The plasma content of oestradiol in oestrous females was significantly higher than during anoestrus, but secretion of this steroid was not increased by any means. The plasma concentration of progesterone in anoestrous females was significantly higher than during oestrus. It was increased by GnRF in anoestrous ferrets and less markedly in oestrous females. The plasma concentration of androstenedione was raised by GnRF to a greater extent during anoestrus than during oestrus. Testosterone was present in higher concentration in the plasma during anoestrus than during oestrus, and the level was increased by GnRF administration. These findings indicate that the ovaries of the anoestrous ferret secrete significant quantities of steroid hormones, and that they respond readily to gonadotrophic hormone.

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Laboratory Analysis of Blood Samples from Patients Treated with Tinzaparin

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-2004-823003 ◽

2004 ◽

Vol 30 ◽

pp. 49-55

Keyword(s):

Laboratory Analysis ◽

Blood Samples

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Species Composition of Sand-fly and Occurrence of Cutaneous Leishmaniasis in Owerri North Local Government Area, Imo State

10.47363/jdcrs/2020(1)106 ◽

2020 ◽

pp. 1-5

Author(s):

Ajero C M Ugoji ◽

◽

P N Amaechi A A ◽

Chigbo U N ◽

◽

...

Keyword(s):

Public Health ◽

Local Government ◽

Species Composition ◽

Cutaneous Leishmaniasis ◽

Local Government Area ◽

Laboratory Analysis ◽

Sand Fly ◽

Blood Samples ◽

Imo State ◽

Chi Square Analysis

Cutaneous leishmaniasis (CL) is a neglected tropical disease of public health value vectored by sand-fly in tropical and vegetative regions of the world. This study was carried out between March and September, 2019 to determine species composition of Sand fly and occurrence of cutaneous leishmaniasis in Owerri North Local Government Area of Imo State. Light and paper oil trap were used to trap 204 Sandflies from 3 villages and identified with standard entomological technique based on morphological characteristics. Assessment of the skin for cutaneous leishmaniasis manifestation was carried out on available respondents above 15 years. Blood samples were collected from 42 head of households and emptied into EDTA containers. Laboratory analysis of blood samples was carried out using standard method of staining and microscopy. Result was represented in percentages and subjected to chi-square analysis. The result revealed two sand-fly genera; Phlebotomus (135) and Lutzomyia (69) with abundant rates of 66.17% and 33.82% respectively. The different species were present in the villages sampled and female flies accounted for 45.59% of the collection. There was no typical CL skin manifestation observed among villagers, however, laboratory analysis of the household respondents showed 3(7.14) persons had amastigote form of leis hymenia in their blood. The study reveals occurrence of cutaneous leishmaniasis and its possible vectors in the study area. There is need for public health awareness, health education and application of effective control measures for sand-fly in this area

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