A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm.

A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdominal (AAA) aortic aneurysm. More than 25,000 people from the Swedish Malmo Diet and Cancer Study had information on at least 24 SNPs and were followed up for a median ≥ 18 years. The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS. In Cox regression models, adjusted for traditional cardiovascular risk factors including hypertension, we found significant associations of the BP-GRS, prospectively, with incident TAA (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.081-2.475 comparing the third vs. the first tertile; p = 0.020) but not with either AAA or aortic dissection. Calibration, discrimination and reclassification analyses show modest improvement in prediction using the BP-GRS in addition to the model which used only traditional risk factors. A GRS for hypertension associates with TAA suggesting a link between genetic determinants of BP and aortic disease. The effect size is small but the addition of more SNPs to the GRS might improve its discriminatory capability.

Quantitative analysis of phantom studies of 111In and 68Ga imaging of neuroendocrine tumours.

BACKGROUND: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using 68Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for 111In-SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios. The accuracy of quantification of lesion volume and activity was also investigated to develop an objective evaluation for radionuclide therapy eligibility. The phantom study was performed using the NEMA IEC Body Phantom with six hot spheres having inner diameters of 10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to-background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1. Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the liver and spleen. Clinical acquisition and reconstruction protocols were applied. Line profiles were drawn to evaluate the smallest detectable volume within a given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs adapted to the background and CT-based ROIs were obtained for all SBRs and sphere diameters, allowing for quantification. RESULTS: The 10-mm sphere was not possible to detect in SPECT images. It was detectable in PET images for SBRs of 2.5:1 and higher. In a background corresponding to the activity uptake in the liver, spheres larger than 22-37 mm were detectable in the 111In-SPECT images and spheres larger than 13-22 mm were detectable in the 68Ga-PET images. The maximum activity concentration was accurately quantified for spheres larger than 22 mm in the PET images; however, the quantification was impaired by sphere size and background activity. CONCLUSIONS: It was not possible to detect the 10-mm sphere in any of the SPECT images. In a background corresponding to the activity uptake in the liver, spheres larger than approximately 30 mm were visible in the 111In-SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga-PET images. Sphere diameter and background activity strongly affect the possibility of a correct quantification.

¹8F-fluorocholine PET/CT compared with extended pelvic lymph node dissection in high-risk prostate cancer.

PURPOSE: To compare (18)F-fluorocholine positron-emission tomography/computed tomography (PET/CT) with extended pelvic lymph node dissection (ePLND) for the detection of lymph node metastases in a large cohort of patients with high-risk prostate cancer. MATERIALS AND METHODS: Patients with prostate-specific antigen levels between 20 and 99 ng/mL and/or Gleason score 8-10 cancers, planned for treatment with curative intent following a negative or inconclusive standard bone scan, were investigated with (18)F-fluorocholine PET/CT followed by an ePLND. None of the patients received hormonal therapy prior to these staging procedures. Results for PET/CT were compared on a per-patient basis with histopathology from ePLND. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: PET/CT detected a total of 76 suspected lymph node metastases and four suspected bone metastases in 33 (29 %) of the 112 included patients. Of these, 35 suspected lymph node metastases, only within the anatomical template area of an ePLND, were found in 21 of the patients. Histopathology of the ePLND specimens detected 117 lymph node metastases in 48 (43 %) of the 112 patients. Per-patient sensitivity, specificity, positive and negative predictive values for (18)F-fluorocholine PET/CT for lymph node metastases within the ePLND template were 0.33, 0.92, 0.76 and 0.65, respectively. Only 11 patients had lymph nodes larger than 10 mm that would have been reported by CT alone. CONCLUSIONS: (18)F-fluorocholine PET/CT detects lymph node metastases in a significant proportion of patients with high-risk prostate cancer with a high specificity, but low sensitivity.

A niobium water target for routine production of [¹8F]Fluoride with a MC 17 cyclotron.

A [(18)F]Fluoride water target was constructed for a Scanditronix MC 17 cyclotron, without a beam line, with a typical wide beam of ∼30 × 5 mm(2). Niobium was used as target chamber material. One hour irradiation with 45µA protons yields about 110 GBq [(18)F]Fluoride. The saturation yield is 8.0 ± 0.6 GBq/µA (EOB). The FDG yield is 60 ± 5% (EOS) with a TracerLab MX (G.E. Healthcare). More than 100 GBq FDG is routinely produced after a 2h irradiation.

Regional cerebral metabolic rate (positron emission tomography) during inhalation of nitrous oxide 50% in humans.

BACKGROUND: Recent studies in man have shown that cerebral blood flow increases during inhalation of nitrous oxide (N2O), a finding which is believed to be a result of an increased cerebral metabolic rate (CMR). However, this has not previously been evaluated in man. METHODS: Regional CMR(glu) (rCMR(glu)) was measured three dimensionally with positron emission tomography (PET) after injection of 2-(18F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. RESULTS: Global CMR(glu) in young men was 27 (3) micromol 100 g(-1) min(-1) [mean (SD)]. Inhalation of N2O 50% did not change global CMR(glu) [30 (5) micromol 100 g(-1) min(-1)] significantly, but it changed the distribution of the metabolism in the brain (P<0.0001 analysis of variance). Compared with inhalation of O2 30% in N2, N2O 50% inhalation increased the metabolism in the basal ganglia [14 (17)%, P<0.05] and thalamus [22 (23) %, P<0.05]. There was a prolonged metabolic effect of N2O inhalation seen on a succeeding PET scan with oxygen-enriched air (P<0.0001) performed 1 h after the N2O administration. CONCLUSIONS: Inhalation of N2O 50% did not change global CMR(glu), but the metabolism increased in central brain structures, an effect that was still present 1 h after discontinuation of N2O.

Carotenoid and protein supplementation have differential effects on pheasant ornamentation and immunity.

A currently popular hypothesis states that the expression of carotenoid-dependent sexual ornaments and immune function may be correlated because both traits are positively affected by carotenoids. However, such a correlation may arise for another reason: it is well known that immune function is dependent on nutritional condition. A recent study has suggested that the expression of ornaments may too depend on nutritional condition, as males in good nutritional condition are better at assimilating and/or modulating carotenoids. Thus, carotenoid-dependent ornaments and immune function may be correlated because both are dependent on nutritional condition. To elucidate if, and how, ornamentation and immune function are linked, pheasant diets were supplemented with carotenoid and/or protein in a fully factorial experiment. Carotenoid treatment affected wattle coloration and tail growth, but not cellular or humoral immunity. Immunity was unrelated to males' initial ornamentation including wattle colour. Males in better body condition, measured as residual mass, increased their wattle coloration more when carotenoid supplemented. Protein positively affected humoral but not cellular immunity, but had no effect on ornaments. Cellular, but not humoral, immunity increased with male body condition. Thus, there was no evidence that an immune-stimulatory effect of carotenoids resulted in wattle coloration honestly signalling immune function, but wattle coloration may still signal male body condition.

Sodium/iodide-symporter: distribution in different mammals and role in entero-thyroid circulation of iodide.

UNLABELLED: The sodium (Na+)/iodide (I-)-symporter (NIS) is abundantly expressed and accumulates iodide in thyroid follicular cells. The NIS is also found in extrathyroidal tissues, particularly gastric mucosa. Controversies exist on the localization of extrathyroidal NIS. We have studied the presence of both NIS peptide and NIS messenger RNA (mRNA) in the digestive tract and thyroid from different mammals. The role of gastric NIS is enigmatic and we aimed to unravel its possible involvement in iodide transport. METHODS: Distribution and expression of NIS were studied using immunocytochemistry and in situ hybridization. Iodide transport in the gastrointestinal tract was measured after oral or intravenous (i.v.) administration of 125I to rats with or without ligation of the pylorus. RESULTS: All thyroid follicular cells in rat and mouse expressed NIS, whereas a patchy staining was noted in man, pig and guinea-pig. Gastric mucosa surface epithelium in all species and ductal cells of parotid gland in guinea-pig, rat and mouse expressed NIS. In parietal cells and in endocrine cells of intestines and pancreas NIS immunoreactivity but no NIS mRNA was found. Studies of 125I uptake showed marked iodide transport from the circulation into the gastric lumen. CONCLUSIONS: The localization of NIS varies slightly among mammals. To establish expression of NIS in a particular cell type the need to correlate the presence of both NIS protein by immunocytochemistry and NIS mRNA by in situ hybridization is emphasized. An entero-thyroidal circulation of iodide mediated principally by gastric NIS, but possibly also by NIS in salivary glands is suggested.

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs.

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.

Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O).

BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. METHODS: Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. RESULTS: Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. CONCLUSIONS: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.

Cerebral glucose metabolism measured by positron emission tomography in term newborn infants with hypoxic ischemic encephalopathy.

Total and regional cerebral glucose metabolism (CMRgl) was measured by positron emission tomography with 2-((18)F) fluoro-2-deoxy-D-glucose ((18)FDG) in 20 term infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. All infants had signs of perinatal distress, and 15 were severely acidotic at birth. Six infants developed mild HIE, twelve moderate HIE, and two severe HIE during their first days of life. The positron emission tomographic scans were performed at 4-24 d of age (median, 11 d). One hour before scanning, 2-3.7 MBq/kg (54-100 microCi/kg) (18)FDG was injected i.v. No sedation was used. Quantification of CMRgl was based on a new method employing the glucose metabolism of the erythrocytes, requiring only one blood sample. In all infants, the most metabolically active brain areas were the deep subcortical parts, thalamus, basal ganglia, and sensorimotor cortex. Frontal, temporal, and parietal cortex were less metabolically active in all infants. Total CMRgl was inversely correlated with the severity of HIE (p < 0.01). Six infants with mild HIE had a mean (range) CMRgl of 55.5 (37.7-100.8) micromol.min(-1).100 g(-1), 11 with moderate HIE had 26.6 (13.0-65.1) micromol.min(-1).100 g(-1), and two with severe HIE had 10.4 and 15.0 micromol.min(-1).100 g(-1), respectively. Five of six infants who developed cerebral palsy had a mean (range) CMRgl of 18.1 (10.2-31.4) micromol.min(-1).100 g(-1) compared with 41.5 (13.0-100.8) micromol.min(-1).100 g(-1) in the infants with no neurologic sequela at 2 y. We conclude that CMRgl measured during the subacute period after perinatal asphyxia in term infants is highly correlated with the severity of HIE and short-term outcome.

Early nutrition causes persistent effects on pheasant morphology.

Differences in growth conditions during early ontogeny have been suggested to cause permanent effects on the morphology and quality of birds. Yearly variation in growth conditions could thus result in morphological and quality differences between cohorts. In this study, we investigated the effect of small differences in the dietary protein content of captive ring-necked pheasants (Phasianus colchicus) during their first 8 wk posthatching. An experimental increase of the proportion of dietary protein during the first 3 wk of life accelerated growth, whereas a similar manipulation during the following 5 wk had only a limited effect. Compensatory growth during the postexperimental period equalized the size of chicks from different experimental treatments. However, a difference in tarsus length resulting from experimental treatment during the first 3 wk remained into adulthood. Furthermore, the protein content of the diet during the first 3 wk had an effect on the degree of fluctuating asymmetry in tarsus length, suggesting persistent effects on the quality of birds. The results of this study may explain size differences between cohorts that exist in pheasants and may also provide a link between the use of pesticides in agriculture and population effects on pheasants.

Postoperative analgesia at home after ambulatory hand surgery: a controlled comparison of tramadol, metamizol, and paracetamol.

We compared in a prospective, randomized, double-blinded study the analgesic efficacy of three drugs in 120 ASA I and II patients scheduled to undergo ambulatory hand surgery with IV regional anesthesia. At discharge, oral analgesic tablets were prescribed as follows: tramadol 100 mg every 6 h, metamizol 1 g every 6 h, and paracetamol (acetaminophen) 1 g every 6 h. Rescue medication consisted of oral dextropropoxyphene 100 mg on demand. Analgesic efficacy was evaluated by self-assessment of pain intensity by visual analog score at six different time intervals during the 48-h study period. Patients also recorded global pain relief on a 5-grade scale, total number of study and rescue analgesic tablets, frequency and severity of adverse effects, sleep pattern, and overall satisfaction. None of the study drugs alone provided effective analgesia in all patients. The percentage of patients who required supplementary analgesics was 23% with tramadol, 31% with metamizol, and 42% with acetaminophen. Tramadol was the most effective analgesic, as evidenced by low pain scores, least rescue medication, and fewest number of patients with sleep disturbance. However, the incidence of side effects was also increased with tramadol. Seven patients (17.5%) withdrew from the study because of the severity of nausea and dizziness associated with the use of tramadol. Metamizol and acetaminophen provided good analgesia in about 70% and 60% of patients, respectively, with a decreased incidence of side effects. Despite receiving oral analgesic medication, up to 40% of patients undergoing hand surgery experienced inadequate analgesia in this controlled trial. Although tramadol was more effective, its use was associated with the highest frequency and intensity of adverse effects and the most patient dissatisfaction. Metamizol and acetaminophen provided good analgesia with a small incidence of side effects. For patients undergoing ambulatory hand surgery, postoperative pain can last longer than 2-3 days, and there is a need for both better education before the procedure and oral analgesic therapy at home.

Glucose utilisation in the lungs of septic rats.

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose ((18)FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of (18)FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. (18)FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions.

Comparison of 125I- and (111)In-labeled monoclonal antibody BR96 for tumor targeting in combination with extracorporeal immunoadsorption.

Extracorporeal whole blood immunoadsorption (ECIA) accelerates the clearance of radiolabeled monoclonal antibodies (mAbs) without significantly affecting tumor uptake by removing the excess of these mAbs from the blood, thus increasing tumor:normal tissue (T:N) ratios. The present study is focused on comparing the capacity of ECIA in tumor targeting with the same mAb (chiBR96-biotin) labeled with either (111)In or 125I. Forty-five Brown Norwegian rats with syngeneic rat colon carcinoma isografted both in liver and intramuscularly were used. chiBR96 is a highly tumor-specific mAb directed against the Lewis-type antigen. ECIA of whole blood was started 15 h after the injection of 125I- or (111)In-labeled BR96-biotin. The procedure lasted for 2 h and was repeated for (111)In-labeled BR96-biotin in a few rats after 3 or 24 h. ECIA reduced the whole body activity by the same magnitude (between 39% and 52%), irrespective of whether (111)In- or 125I-labeled chiBR96 was used. A similar observation was also made for the reduction in blood radioactivity after ECIA (79-94%). Time-activity curves during ECIA showed that the major reduction (approximately 85%) in blood radioactivity occurred during the first 45-60 min. Repeating the ECIA with (111)In-BR96 caused only an additional minimal reduction of blood activity, whereas a further reduction of whole body activity of 14-20% was achieved. The T:N uptake ratios were significantly enhanced immediately after ECIA with (111)In- or 125I-labeled chiBR96. Due to greater accumulation of (111)In-BR96 in tumors, a long-term improvement in T:N ratios was obtained after ECIA compared with 125I-labeled BR96. Our results therefore indicate that (111)In/(90Y)-labeled BR96-biotin could be more advantageous than 125I/131I for radioimmunotargeting/radioimmunotherapy in combination with ECIA due to better activity retention by the tumor.

Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas.

Experience in using rapidly internalizing antibodies, such as the anti-CD22 antibody, for radioimmunotherapy of B-cell lymphomas is still limited. The present study was conducted to assess the efficacy and toxicity of a 131I-labeled anti-CD22 monoclonal antibody (mAb), LL2, in patients with B-cell lymphomas failing first- or second-line chemotherapy. Eligible patients were required to have measurable disease, less than 25% B cells in unseparated bone marrow, and an uptake of 99mTc-labeled LL2Fab' in at least one lymphoma lesion on immunoscintigram. Eight of nine patients examined with immunoscintigraphy were unequivocally found to have an uptake, and therapy with 131I-labeled anti-CD22 [1330 MBq/m2 (36 mCi/m2)] preceded by 20 mg of naked anti-CD22 mAb was administered. Three patients achieved partial remission (duration, 12, 3, and 2 months), and one patient with progressive lymphoma showed stable disease for 17 months. Four patients exhibited progressive disease. The toxicity was hematological. Patients with subnormal counts of neutrophils or platelets before therapy seemed to be more at risk for hematological side effects. Radioimmunotherapy in patients with B-cell lymphomas using 131I-labeled mouse anti-CD22 can induce objective remission in patients with aggressive as well as indolent lymphomas who have failed prior chemotherapy.

Dopamine D2-receptor density in humans as assessed with SPET and the new high-affinity ligand 123I-NCQ298: a pilot study.

Astra (S)-3-[123I]iodo-5,6-dimethoxyl-N-[(1-ethyl-2-pyrrolidinyl)methyl] -salicylamide (123I-NCQ298) is a new high-affinity D2-receptor ligand for use in single photon emission tomography (SPET) studies. We have studied the biodistribution and absorbed radiation dose of 123I-NCQ298 in humans. The mean effective dose for adults was 0.055 mSv MBq(-1). Brain uptake and clearance was measured with a head dedicated SPET camera. 123I-NCQ298 showed specific uptake in the basal ganglia with a low clearance rate (time constant of 9-34 h). The extrastriatal binding was variable (average 30%, maximum 60% of that in the basal ganglia at 1 h), but with a clearance rate twice that of the basal ganglia. The fairly high level of extrastriatal binding precluded the use of a quotient between the basal ganglia and cerebellum-to-frontal cortex 123I-NCQ298 concentration as a measure for basal ganglia D2-receptor density. Chronic schizophrenic patients treated with conventional neuroleptics had a decreased affinity for 123I-NCQ298 in the basal ganglia in the range 10-60% of the median value for the control, untreated subjects.

An alternative method to normalize clinical FDG studies.

UNLABELLED: An alternative method of determining the integrated input function, necessary in the quantitative [18F]fluorodeoxyglucose (FDG) autoradiographic model, has been developed. Using erythrocytes as reference tissue, researchers require only one blood sample after injection of FDG to obtain the integrated input function. METHODS: The amount of FDG-6-PO4 in the erythrocytes is proportional to their exposure to FDG, that is, the integrated input function. Free FDG is removed by washing the erythrocytes twice. Inter- and intraindividual differences of the metabolic rate of erythrocytes are corrected for by an in vitro incubation with a known amount of FDG. RESULTS: Validation of the proposed method was done by correlating the integrated input function, based on the glucose metabolism of the erythrocytes, to the integrated input function obtained by multiple venous blood samples. The new method provides the integrated input function with an accuracy better than +/-8%. CONCLUSION: By using erythrocytes as a reference tissue, researchers can determine the integrated input function in the quantitative FDG autoradiographic model with an accuracy sufficient for clinical PET studies. The simplicity of the method also makes it suitable for FDG studies on small children. With two samples, the method can also be used for a simplified graphical Patlak analysis.