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Objectives: To assess the efficacy and safety of 99m Tc-TRODAT-1 SPECT in diagnosing Parkinson's disease (PD)., Methods: 99m Tc-TRODAT-1 SPECT imaging was performed in 34 healthy controls and 96 PD patients 2.5 h later after injection. The striatal image was evaluated visually and semi-quantitively. Sensitivity and specificity of 99m Tc-TRODAT-1 SPECT were analyzed according to Hoehn and Yahr scale (HYS). Based on HYS, the PD patients were divided into mild (HYS 1-2) and moderate (HYS 3-5) groups. The uptake ratios of striatum (ST) and cerebellum (CB) in contralateral, ipsilateral and bilateral striatum in different groups were calculated and analyzed. The safety was assessed., Results: The sensitivity and specificity of 99m Tc-TRODAT-1 SPECT to discriminate PD patients from healthy subjects were 98.96% and 94.12% and it has perfect agreement with HYS (κ = 0.94, p < 0.001). The sensitivity to diagnose mild and moderate PD was 43.42% and 95% separately. The uptake ratio in PD patients was significantly lower than that in healthy controls (1.37 ± 0.13 vs 1.68 ± 0.18, p < 0.001). And the uptake ratio in contralateral side was markedly reduced in unilateral PD patients as compared with the ipsilateral side (1.50 ± 0.20 vs 1.46 ± 0.21, p < 0.001). The striatal uptakes in affected striatum and bilateral striatum were reduced with increasing disease severity between healthy control versus mild stage versus moderate stage in the affected striatum and bilateral striatum in PD patients. No serious adverse events or death was observed after injecting 99m Tc-TRODAT-1., Conclusion: We demonstrated that 99m Tc-TRODAT-1 was a safety radiotracer which can be used in clinic to diagnose PD using SPECT.

Doxorubicin (DOX) is a potent chemotherapeutic with distinct cardiotoxic properties. Understanding the underlying cardiotoxic mechanisms on a molecular level would enable the early detection of cardiotoxicity and implementation of prophylactic treatment. Our goal was to map the patterns of different radiopharmaceuticals as surrogate markers of specific metabolic pathways induced by chemotherapy. Therefore, cardiac distribution of 99m Tc-sestamibi, 99m Tc-Annexin V, 99m Tc-glucaric acid and [ 18 F]FDG and cardiac expression of Bcl-2, caspase-3 and -8, TUNEL, HIF-1α, and p53 were assessed in response to DOX exposure in mice. A total of 80 mice (64 treated, 16 controls) were evaluated. All radiopharmaceuticals showed significantly increased uptake compared to controls, with peak cardiac uptake after one ( 99m Tc-Annexin V), two ( 99m Tc-sestamibi), three ([ 18 F]FDG), or four ( 99m Tc-glucaric acid) cycles of DOX. Strong correlations (p < 0.01) were observed between 99m Tc-Annexin V, caspase 3 and 8, and TUNEL, and between [ 18 F]FDG and HIF-1α. This suggests that the cardiac DOX response starts with apoptosis at low exposure levels, as indicated by 99m Tc-Annexin V and histological apoptosis markers. Late process membrane disintegration can possibly be detected by 99m Tc-sestamibi and 99m Tc-glucaric acid. [ 18 F]FDG signifies an early adaptive response to DOX, which can be further exploited clinically in the near future.

Objective: Technetium etarfolatide ((99m)Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors. Administering folic acid prior to the administration of (99m)Tc-EF has been shown to improve SPECT images. Here, we conducted a phase I clinical trial to assess the safety, pharmacokinetics, and radiation dosimetry of (99m)Tc-EF injection following pre-administration of folic acid in healthy Japanese male adults., Methods: Six healthy Japanese male adults were enrolled in the study. Folic acid was intravenously administered, followed 1-3 min later by an intravenous injection of (99m)Tc-EF (740 MBq ± 20 %). Assessments of subjective symptoms and objective findings, electrocardiograms, physical examination, and laboratory tests were performed before and up to 7 days after the injection to assess the safety of (99m)Tc-EF. Blood and urine collections and whole-body planar imaging were conducted at various time points up to 24 h after the injection to assess the pharmacokinetics of (99m)Tc-EF. The internal radiation dosimetry was calculated based on the pharmacokinetics results using the MIRD method., Results: Five adverse events were observed in three subjects (50 %) after administration of the folic acid and (99m)Tc-EF, while these events were mild and non-serious. Of those five events, three were considered to be related to the administered agents. The radioactivity in blood rapidly decreased and showed a biphasic profile. The activity of (99m)Tc-EF at 5 min post injection was largest in the bone marrow, followed by the liver and kidneys, and had decreased within 24 h in all organs/tissues without appreciable retention. The pharmacokinetics results suggested that (99m)Tc-EF was mainly eliminated by kidney. The results also suggested that when administered at 925 MBq of (99m)Tc-EF, which is the maximum dose generally used for clinical trials in other countries, the corresponding effective dose of (99m)Tc-EF is equal to or less than those determined for the current radioactive diagnostic imaging agents., Conclusions: The results of this study assessing the safety and radiation dosimetry of (99m)Tc-EF with folic acid pre-administration suggested that folic acid and (99m)Tc-EF should be appropriate for further studies. No pharmacokinetics concerns were noted.

Objective: To measure the organ dose and calculate effective dose from CT attenuation correction (CTAC) acquisitions from four commonly used gamma camera single photon emission CT/CT systems., Methods: CTAC dosimetry data was collected using thermoluminescent dosemeters on GE Healthcare's Infinia™ Hawkeye™ (GE Healthcare, Buckinghamshire, UK) four- and single-slice systems, Siemens Symbia™ T6 (Siemens Healthcare, Erlangen, Germany) and the Philips Precedence (Philips Healthcare, Amsterdam, Netherlands). Organ and effective dose from the administration of (99m)Tc-tetrofosmin and (99m)Tc-sestamibi were calculated using International Commission of Radiological Protection reports 80 and 106. Using these data, the lifetime biological risk was calculated., Results: The Siemens Symbia gave the lowest CTAC dose (1.8 mSv) followed by the GE Infinia Hawkeye single-slice (1.9 mSv), GE Infinia Hawkeye four-slice (2.5 mSv) and Philips Precedence v. 3.0. Doses were significantly lower than the calculated doses from radiopharmaceutical administration (11 and 14 mSv for (99m)Tc-tetrofosmin and (99m)Tc-sestamibi, respectively). Overall lifetime biological risks were lower, which suggests that using CTAC data posed minimal risk to the patient. Comparison of data for breast tissue demonstrated a higher risk than that from the radiopharmaceutical administration., Conclusion: CTAC doses were confirmed to be much lower than those from radiopharmaceutical administration. The localized nature of the CTAC exposure compared to the radiopharmaceutical biological distribution indicated dose and risk to the breast to be higher., Advances in Knowledge: This research proved that CTAC is a comparatively low-dose acquisition. However, it has been shown that there is increased risk for breast tissue especially in the younger patients. As per legislation, justification is required and CTAC should only be used in situations that demonstrate sufficient net benefit.

Introduction: Diagnosis of renal cortical lesions by radioisotopes in nuclear medicine is one of the most common techniques and procedures can be performed by different radiotracer. However, all these materials are accurate in determining kidney function, but there are differences between them in the field. The purpose of this study was to evaluate the effectiveness of EC scans compared with DMSA scan in the detection of cortical lesions and DRF., Methods: 65 cases, which have been referred for various reasons, for DMSA scans were enrolled. Patients 1 week after DMSA scan with the previous consent of the EC being scanned. The results were compared in terms of convergence as well as sensitivity, specificity, positive and negative predictive value of EC with respect to the results of DMSA scan., Results: PPV of EC was 100%, negative predictive value of EC was 68.75%, sensitivity of EC was 90.74% and specificity of EC was 100% in the detection of cortical lesions. DMSA scan and EC convergence rates result in cortical lesions in our study was high., Discussion: We suggest EC scan as an alternative to reduce the cost of therapy and radiation, but considering the benefits of DMSA scan, it could remain the gold standard method of diagnosis.

Purpose: Tc N-MPO ([Tc N(MPO)(PNP5)]: HMPO = 2-mercaptopyridine N-oxide, and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a new Tc radiotracer useful for myocardial perfusion imaging. This study was designed to determine its pharmacokinetics and biodistribution in healthy volunteers., Patients and Methods: Ten healthy volunteers were involved in this study. Each subject was administered approximately 925 MBq of Tc N-MPO under rest or stress conditions (n = 5 per group). Whole-body planar images were obtained at 10, 30, 60, 240, and 1440 minutes after injection. Organ uptake was quantified by region-of-interest analysis. The blood clearance and urine excretion kinetics were determined by collecting blood and urine samples at different time points., Results: Tc N-MPO showed significant accumulation in myocardium with prolonged retention. At rest, its percentage of injected dose (%ID) uptake in the heart, lungs, and liver at 10 minutes after injection was 2.47% (0.64%), 1.84% (0.64%), and 20.88% (5.23%), respectively. The liver uptake decreased to 6.79%ID (1.60%ID) at 60 minutes after injection and 4.50%ID (1.86%ID) at 240 minutes after injection. Under stress conditions, the heart uptake was slightly increased (2.57%ID [0.21%ID]). The rapid liver clearance led to favorable heart-to-liver ratios, reaching values of 0.27%ID (0.07%ID) under rest condition and 0.28%ID (0.05%ID) under stress condition at 60 minutes after injection., Conclusions: Tc N-MPO demonstrates a highly favorable biodistribution in humans. The high heart uptake and the fast liver washout of Tc N-MPO will allow SPECT images of the left ventricle to be acquired as early as 10 minutes after injection.

Purpose: Neurotensin subtype 1 receptor overexpression is found in a variety of human tumors. The aim of this pilot/phase I study was to assess the safety profile, pharmacokinetics, and imaging characteristics of (99m)Tc-Demotensin VI in tumor patients., Methods: Scintigraphy with (99m)Tc-Demotensin VI was performed in 14 patients (2 female and 12 male) with advanced tumor stages. The diagnoses were pancreatic adenocarcinoma (n=4), small cell lung cancer (SCLC) (n=4), non-small cell lung cancer (NSCLC) (n=4), and colon carcinoma (n=2). Patients were injected with 500-550 MBq (99m)Tc-Demotensin VI. Blood samples were taken at various time points and urine was also collected up to 24 hours post-injection (p.i.) Planar images were acquired at 15-30 minutes, 1-2 hours, 4 hours, and 24 hours p.i. with additional SPECT imaging at 4 hours., Results: Radiochemical purity always exceeded 95% up to 4 hours. Urinary and blood excretion was rapid with 5.05% ID (mean: n=5) in plasma after 4 hours. No side effects were observed after injection of (99m)Tc-Demotensin VI. Focal tracer accumulation was observed in 3 patients with brain metastases due to NSCLC, although specificity of this uptake could not be proven. Further, no tumor-related findings were observed. Although stability tests in human plasma revealed that (99m)Tc-Demotensin VI remained intact up to 2 hours incubation, ex vivo urine analysis indicated rapid metabolism., Conclusion: (99m)Tc-Demotensin VI was well tolerated by patients and showed favorable pharmacokinetics; however, tumor targeting was limited to brain metastases. Further studies on stability issues and receptor characterization in tumors are warranted to introduce neurotensin receptors (NTSR) imaging into the clinic.

Objectives: Pre-clinical experiments demonstrated that intravenous (99m)Tc labelled DI-DD-3B6/22-80B3 humanised anti-fibrin-D-dimer Fab' fragments ((99m)Tc-DI-80B3) allowed scintigraphic imaging of acute pulmonary emboli (PE). The aims of this clinical study were to determine the safety of (99m)Tc-DI-80B3 in patients with PE and evaluate the resulting scintigraphic images for the localisation of acute PE., Materials/patients and Methods: (99m)Tc-DI-80B3 (0.5mg, 710-850MBq) was administered intravenously to subjects (n=14) with segmental or larger PE on recent contrast-enhanced helical CT scans. Thoracic SPECT scans were acquired 15 minutes, 2 hours and 4 hours afterwards. Subjects were followed for 90 days subsequently., Results: There were no serious adverse events or antibody responses associated with (99m)Tc-DI-80B3 administration. Focal accumulations of (99m)Tc-DI-80B3 on the SPECT images of the thorax acquired at four hours corresponded to pulmonary emboli detected by CT. Two independent "blinded" SPECT readers identified 79% and 71% (respectively) of the right lung and 79% and 64% (respectively) of the left lung in which CT scans disclosed PE., Conclusions: (99m)Tc-DI-80B3 is well-tolerated in patients with acute PE and does not induce an immune response. (99m)Tc-DI-80B3 may offer a novel approach to imaging PE in a clinically acceptable timeframe without exposure to potentially nephrotoxic radiographic contrast agents., (Copyright © 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.)

Unlabelled: We encountered local reactions at injection sites in 7 patients after an intravenous injection of (99m)Tc-hydroxymethylene diphosphonate ((99m)Tc-HDP). Archived bone scans showed radiopharmaceutical extravasation at injection sites in all patients. To identify the mechanism underlying these local reactions, we challenged BALB/c mice with an (99m)Tc-HDP injection and investigated the mechanism involved., Methods: Seven solutions were prepared: 0.1 M acetic acid, 0.1 M NaOH, 2.1 mM (99m)Tc-HDP, 4.7 mM (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), 1.05 mM (99m)Tc-HDP diluted with normal saline, 37 MBq of (99m)Tc-pertechnetate, and normal saline. Six female BALB/c mice were subcutaneously injected in their backs with 0.04 mL of each solution. Backs were observed, and skin and subcutaneous tissues were acquired on days 5, 7, and 19 after injection. Two pathologists interpreted the histologic specimens., Results: The pH values of the 0.1 M acetic acid, 0.1 M NaOH, 2.1 mM (99m)Tc-HDP, 4.7 mM (99m)Tc-MDP, 1.05 mM (99m)Tc-HDP diluted with normal saline, 37 MBq (99m)Tc-pertechnetate, and normal saline were 3.28, 14.3, 4.79, 6.45, 6.16, 6.85, and 6.53, respectively. A slight redness was observed at (99m)Tc-HDP injection sites on day 5 after injection, and many inflammatory cells, such as neutrophils, were found to infiltrate subcutaneous tissues by light microscopy, suggesting active inflammation. However, no abnormality was found at (99m)Tc-MDP injection sites. On day 19, (99m)Tc-HDP injection sites appeared to have recovered and showed healed scars and almost-normal microscopic features., Conclusion: Our results indicate that the local reaction induced by extravasation of (99m)Tc-HDP is probably caused by high acidity, and (99m)Tc-HDP should be administered carefully to avoid adverse reactions.

Objective: Occasionally, either for urgent diagnostic reasons or by accident, pregnant women are exposed to technetium scintigraphy, the consequences of which were unknown, due to lack of systematic data. Therefore, clinical data was needed to assess the risk and safety of technetium scintigraphy with respect to prenatal development., Methodology: Requests for information with regard to technetium scintigraphy from pregnant women or their physicians were followed by the Berlin Institute for Clinical Teratology. A prospective observational cohort study was performed using data collected between 1991 and 2008. Pregnancy outcome for a cohort of pregnant women exposed to Tc-99m-scintigraphy of thyroid (n=102) or bone (n=20) during pregnancy was compared with a control group without teratogenic exposure (n=366)., Results: Major birth defects were no more common in the study group than in the control group (OR 1.00; 95% CI 0.23-3.38) and no specific pattern of birth defects was found. Spontaneous abortion rate (OR 0.51), preterm deliveries, and birth measurements of newborns were not significantly different from controls., Conclusion: This prospective observational study suggests that the inadvertent exposure to Tc-99m-scintigraphy in early pregnancy is relatively safe for the fetus.

Objective: To study the safety, biodistribution, and dosimetry of myocardial perfusion imaging agent 99Tc(m)N-NOET in 10 healthy volunteers., Methods: 744-792 MBq of 99Tc(m)N-NOET was injected to each volunteer. Safety parameters and adverse event was measured in 24 hours of injection. Biodistribution was studied by whole-body imaging 1, 30 minutes, 1, 2, 4, 8, and 24 hours after the injection of 99Tc(m)N-NOET. The estimation of dosimetry was based on the standard medical internal radiation dose method using MIRDOSE 3.0 analysis program. Myocardial single photon emission computed tomography (SPECT) imaging was performed at 1 and 4 hours after injection., Results: No undesirable effects were reported by the subject during 24 hours after injection of 99Tc(m)N-NOET. No clinically significant changes were found in vital signs (heart rate, blood pressure, and electrocardiogram). No biochemical aspects and serology changes were measured. The myocardial SPECT imaging was clear. Cardiac uptake of 99Tc(m)N-NOET was as high as 2.68% at 2 hours after injection. The heart to lung ratio was more than 1 from 30 minutes after injection, reaching a maximum of 1.91 +/- 0.53 at 2 hours after injection. Radiation dosimetry calculations indicated an effective absorbed dose of 1.28 x 10(-5) Sv/MBq. The dosimetry in each main organ is lower then 50 mGy given 740 MBq of 99Tc(m)N-NOET in once imaging., Conclusions: 99Tc(m)N-NOET exhibits high cardiac uptake and low estimated effective absorbed dose. It's a safe myocardial perfusion imaging agent.

Unlabelled: Interleukin 8 (IL-8) is a chemotactic cytokine that binds with a high affinity to receptors expressed on neutrophils. Previous studies with various animal models showed that (99m)Tc-labeled IL-8 accumulates specifically and rapidly in infectious and inflammatory foci. The aims of the present study were to evaluate the safety of IL-8 in humans and to assess the value of (99m)Tc-IL-8 scintigraphy in patients with suspected localized infections., Methods: (99m)Tc-IL-8 was intravenously injected at 400 MBq into 20 patients with various suspected localized infections. Patients were monitored for IL-8-related side effects for 4 h. Whole-body imaging was performed directly after injection and at 4 h after injection. Imaging after 24 h was performed for the first 7 patients and for subsequent patients when the results of (99m)Tc-IL-8 scintigraphy at 4 h after injection were normal or equivocal. Blood was drawn at several time points to determine the total number of leukocytes and leukocyte differentiation (all patients) and to determine pharmacokinetics (6 patients)., Results: (99m)Tc-IL-8 scintigraphy was performed for 20 patients (13 men and 7 women) with a mean age of 60 y (range, 21-76 y). No significant side effects were noted. Patients had suspected joint prosthesis infections (n = 9), osteomyelitis (n = 8), liver abscess (n = 1), and soft-tissue infections (n = 2). (99m)Tc-IL-8 was rapidly cleared from the blood and most other organs. In 10 of 12 patients with infections, (99m)Tc-IL-8 localized the infection at 4 h after injection. In 1 patient with vertebral osteomyelitis and in 1 patient with an infected knee prosthesis, (99m)Tc-IL-8 scintigraphy results were false-negative. In 8 patients with noninfectious disorders, no focal accumulation of (99m)Tc-IL-8 was found., Conclusion: Injection of (99m)Tc-IL-8 is well tolerated. (99m)Tc-IL-8 scintigraphy is a promising new tool for the detection of infections in patients as early as 4 h after injection.

Purpose: (99m)Tc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to (99m)Tc-DI-80B3 Fab') is a humanised, radiolabelled monoclonal antibody Fab' fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of (99m)Tc-DI-80B3 Fab' in healthy volunteers., Methods: Thirty-two healthy volunteers (18-70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of (99m)Tc-DI-80B3 Fab'. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology., Results: No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. (99m)Tc-DI-80B3 Fab' had a rapid initial plasma clearance (t (1/2)alpha=1 h). The pharmacokinetic profile of the Fab' fragment was generally linear across the four dose cohorts. By 24 h, 30-35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq., Conclusions: (99m)Tc-DI-80B3 Fab' is well tolerated, is rapidly cleared and exhibits clinically acceptable dosimetry-characteristics well suited to a potential thrombus imaging agent.

A bis-(N-sec-butyl dithiocarbamato) nitrido technetium-99m complex [(99m)TcN(SBDTC)2] (SBDTC: N-sec-butyl dithiocarbamato) was synthesized by the reduction of (99m)TcO4(-) to [(99m)Tc[triple bond]N]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of sodium N-sec-butyl dithiocarbamate dihydrate. The radiochemical purity of the complex was over 90% as measured by thin layer chromatography. It was stable over 6 h at room temperature. Its partition coefficient indicated that it was a good lipophilic complex. The electrophoresis results showed that the complex was neutral. Biodistribution studies in mice demonstrated that the complex accumulated in the brain with high uptake and good retention. The brain uptake (ID%/g) was 3.89, 3.44 and 2.82 and the brain/blood ratio was 1.41, 1.45, 1.00 at 5, 30 and 60 min post-injection respectively. These results suggested the potential usefulness of the complex as a brain perfusion imaging agent.

We report the preclinical testing of a synthetic receptor-binding macromolecule, [(99m)Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K(D) = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [(99m)Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 +/- 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10(-2) mSv/MBq. This preclinical study demonstrates that [(99m)Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.

Organ residence times were calculated for diagnostic intakes of (99m)Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG(3)) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity ( S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 microGy MBq(-1) respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG(3), and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 microGy MBq(-1). With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG(3) the maternal contribution to total foetal body dose exceeded 93% for both stages.

The aim of this study was to assess the safety and biodistribution of technetium-99m BRU 59-21, a novel radioactively labelled 2-nitro-imidazole hypoxic marker, in head and neck cancer patients and to correlate uptake with pimonidazole staining. (99m)Tc-BRU 59-21 was administered intravenously (mean dose 824 MBq, range 780-857 MBq) to ten head and neck cancer patients scheduled for primary surgery, and whole-body images and SPET scans were then obtained. Uptake of radioactivity in the regions of interest was determined and tumour to normal tissue ratios were calculated after correlative evaluation with MRI/CT. Twelve to 16 h before surgery (up to 2 weeks after the scan), patients received pimonidazole intravenously. Tumour sections were stained immunohistochemically for pimonidazole binding. No serious adverse events were reported. In five patients there were ten adverse events, which were mild in intensity and resolved completely without intervention. Uptake of (99m)Tc-BRU 59-21 was observed in eight of the ten primary tumours. Tumour to normal tissue ratios on the SPET scans for primary tumour and lymph nodes increased from 1.8 (range 0.9-2.7) to 2.1 (range 0.8-3.7) between 30 min and 3 h post injection. Tumour to normal tissue ratios in the primary tumour were significantly correlated with pimonidazole staining for SPET scans performed 30 min and 3 h post injection ( P=0.016 and P=0.037, respectively). When primary tumour and involved lymph nodes were considered in conjunction, correlation between the tumour to normal tissue ratio and pimonidazole staining was observed for early ( P<0.001) but not for late SPET scans ( P=0.076). However, late scans showed better tumour delineation than early scans. Administration of (99m)Tc-BRU 59-21 in head and neck cancer patients appears to be safe and feasible. Uptake and retention in tumour tissue was observed, suggestive of tumour hypoxia, and this was supported by correlations with staining for the hypoxic marker pimonidazole.

In vitro-labeled leukocyte imaging is useful for the detection of infection, but an in vivo labeling method is preferable. This study sought to evaluate the safety and efficacy of a leukocyte-avid peptide for the detection of infection, to determine the effects of peptide dose on performance and to compare the peptide with in vitro-labeled leukocytes. A 23-amino acid peptide, P483, containing the platelet factor-4 heparin-binding sequence, was labeled with 99mTc and complexed with heparin (P483H). Thirty patients were injected with 29 microg (n = 11), 145 microg (n = 10) or 290 microg (n = 9) of labeled peptide, and imaged 15 min and 90-120 min later. Early and late images were interpreted individually and jointly. Twenty patients underwent (111)In-labeled leukocyte scintigraphy. Fourteen patients had infection: osteomyelitis (n = 7), vascular graft (n = 2), abscess (n = 2), joint replacement (n = 1), surgical wound (n = 1) and pneumonia (n = 1). There were 10 adverse events in six patients; all were mild and resolved spontaneously, and without any intervention. The sensitivity, specificity and accuracy were the same for both early and late imaging: 0.86, 0.81 and 0.83, respectively. Interpreting early and late images together did not improve the results. No relationship between peptide dose and study accuracy was found. In patients undergoing both examinations, the accuracies of the peptide and in vitro-labeled leukocyte imaging were identical: 0.80. In summary, 99mTc-P483H safely, rapidly and accurately detected focal infection, was comparable with in vitro-labeled leukocyte imaging and therefore merits further investigation.

This phase I pilot study reports on (1) the safety and feasibility of 99Tc(m)-HL91, an amine oxime core radioligand that has shown oxygen dependent binding, and imaging; and (2) its usefulness for the visualization of local tumour recurrence of a biopsy proven squamous cell carcinoma of the head and neck (SCCHN) as compared to spiral computed tomogaphy (CT) and biopsy. Nine men (mean age 33 years, range 34-74 years) were prospectively included. For safety measurements, vital signs were recorded and serum chemical analysis carried out, with a complete blood cell count and urine analysis, and an ECG was performed prior to injection of 99Tc(m)-HL91 and repeated during the investigation. Single photon emission computed tomography (SPECT) scans of the head and neck, and of a standard, were performed at 2 h and 4 h post-injection of 740 MBq 99Tc(m)-HL91. Tumour-to-normal tissue background (T/N) ratios and percentage uptake were measured for all 99Tc(m)-HL91 scans. Spiral CT scans were obtained using a Somaton 4+ Siemens scanner within 1 week from the 99Tc(m)-HL91 scans. Based on CT and the 99Tc(m)-HL91 scan findings guided biopsies were performed. No adverse or subjective side effects were noticed. Vital signs, ECG findings, clinical laboratory, blood and urine assays remained stable in all patients. Spiral CT suggested local recurrence in 5/9 patients accompanied by nodal involvement in three, all of which proved positive on biopsy. 99Tc(m)-HL91 scintigraphy was false positive in one patient and true positive (TP) in 3/5 local recurrences and two out of three sites of lymph node involvement depicted by spiral CT. The mean T/N ratios at 2 h and 4 h in TPs were 1.28 (range 1.1-1.66) and 1.40 (range 1.0-1.6), respectively. The corresponding absolute percentages of 99Tc(m)-HL91 lesional uptake at 2 h and 4 h were mu = 0.05% (SD = 0.03%) and mu = 0.048% (SD = 0.035%). The findings suggest 99Tc(m)-HL91 is a safe radioligand and that metabolic binding in a large fraction but not all of local SCCHN recurrences may be expected. The inference that tumour 99Tc(m)-HL91 avidity could be a non-invasive measure of tumour hypoxia deserves however independent confirmation with needle oximetry.

Unlabelled: In pivotal phase III clinical trials for detecting recurrent or metastatic colorectal cancer, most patients received a single arcitumomab injection. However, the early detection of postsurgical recurrence or metastases with arcitumomab will necessitate serial studies for surveillance. We present immunogenicity, safety, and imaging data supporting the use of multiple administrations of arcitumomab., Methods: Human antimouse antibody (HAMA) response, adverse events, clinical laboratory values, and diagnostic imaging results were evaluated in 44 patients (24 men, 20 women; age range, 2878 y) after repeated arcitumomab administration (44 second and 3 third injections). Most patients initially had Dukes' class B or C colorectal cancer and had known or occult disease recurrence and elevated serum carcinoembryonic antigen levels at the time of the repeated injection., Results: At the repeated injection, in no patient did elevated HAMA titers develop, hematology and serum chemistry changes were clinically insignificant, and only 1 adverse event (eosinophilia) was judged at least possibly related to arcitumomab. Arcitumomab imaging results at the second injection were comparable with those obtained in phase III trials after a single injection of arcitumomab, having a 78% per-lesion concordance with CT in the abdomen and pelvis and a 73% sensitivity and 94% specificity based on 9 patients with cancer confirmed surgically at 11 anatomic sites and excluded at 16 sites., Conclusion: These data indicate that at least 2 injections of arcitumomab can be given safely to patients with colorectal cancer, without increased immunogenicity and with imaging efficacy equivalent to the first administration.

The purpose of this study was to investigate the pharmacologic characteristics of TRODAT-1 (2beta-((N,N'-bis(2-mercaptoethyl)ethylene diamino)methyl), 3beta-(4-chlorophenyl)tropane) labeled with [99mTc] as an imaging agent for dopamine transporter (DAT). Radiochemical purity of [99mTc]TRODAT-1 was over 90%. The partition coefficients in octanol and buffer were 2.12 and 2.19 at pH 7.0 and 7.4, respectively. Animal studies have been performed in rats, rabbits, and normal and hemi-Parkinsonian model monkeys. Biodistribution displayed moderate uptake in rat brain (0.28 %ID/organ at 2 min) and the striatal uptake was 0.193, 0.142, and 0.136 %ID/g at 2, 60, and 120 min, respectively. The ratios of striatal/cerebellar (ST/CB) uptake were 2.4, 4.45, and 2.45 %ID/g at 60, 120, and 240 min, respectively. The major radioactivity was excreted by the hepatobiliary system. Blood clearance kinetics was performed in rabbits, and the initial half-life of 1.18 min and late half-life of 367.8 min were obtained. Brain single photon emission computed tomography imaging studies in normal monkeys showed the ratios of ST/CB uptake were 1.56-2.0 %ID/g and indicated that both uptake and retention in the striatal area were associated with the DAT. The imaging of hemi-Parkinsonian model monkeys also displayed the expected selectivity, the highest uptake being observed in the basal ganglia area of the normal side. Thereby, it is suggested that [99mTc]TRODAT-1 is a safe and useful imaging agent for localization of the presynaptic DAT in the brain.

In the present study, the potential role of 99mTc-PEG-liposome to determine the extent and severity of active disease of Crohn's colitis was investigated. Patients suspected of having an exacerbation of Crohn's disease underwent a 99mTc-PEG-liposome scan (740 MBq, imaging at 4 and 24 h p.i.). A barium enema or endoscopy was performed as the standard verification procedure. Disease activity indices (Clinical Disease Activity Index and Van Hees Activity Index) were calculated. In seven patients positive images of colon segments affected by Crohn's colitis were obtained using 99mTc-PEG-liposomes. Only a moderate relation between 99mTc-liposome scan grading and verification procedures was found (Spearman rank r = 0.22). In accordance with previous studies, no significant correlation was found between the clinical disease activity indices and the verification procedures. This study was prematurely terminated because of unacceptable side-effects in 3 out of 9 patients, which occured almost immediately after starting the infusion. The complaints consisted of dyspnea and facial erythema. The symptoms were self-limiting when the infusion was stopped. In conclusion, the extent of Crohn's colitis can be established non-invasively with 99mTc-PEG-liposome scintigraphy. However, in view of the encountered side-effects, the PEG-liposomal preparation may have to be modified.

99Tcm-citrate has been shown to incorporate irreversibly in the skeleton with a biodistribution different to that on a conventional bone scan. The aims of this study were to confirm the bone-imaging properties of 99Tcm-citrate, to identify the variabilities influencing its skeletal uptake, to compare its uptake in bone with that of 99Tcm-MDP and to assess its possible role in bone scintigraphy. Appropriate animal and human studies (n = 45) were conducted. The 3 h lesion-to-bone ratio of 99Tcm-citrate was compared with that of 99Tcm-MDP in more than 150 lesions, including osteoblastic sites (Group A), lesions undergoing treatment or healing (Group B), and degenerative or old healed lesions (Group C). The uptake ratio was classified as concordant (< 20% variation), mildly discordant (20-50% variation) or significantly discordant (> 50% variation). Animal experiments showed most bone uptake of 99Tcm-citrate when prepared at a pH of 6.0-6.5. The two radiopharmaceuticals appeared to compete for bone uptake, suggesting related but different sites of bone accumulation. The 99Tcm-citrate/99Tcm-MDP uptake ratio in Group A was concordant (mean +/- S.D. = 0.92 +/- 0.15), while Group C lesions had a significantly lower 99Tcm-citrate/99Tcm-MDP uptake ratio (0.34 +/- 0.24, P < 0.01). A comparison of Group B lesions showed wide variation in intensity and area of involvement in many lesions (uptake ratio < 0.5 or > 1.5 in 13 of 30 sites). We conclude that 99Tcm-citrate has a different site of bone localization than phosphonates, possibly in the organic matrix. Although its skeletal uptake is lower than that of 99Tcm-MDP, it may have better specificity in differentiating osteoblastic from degenerated or healed bony lesions, and therefore be useful in predicting healing of bone secondaries, fractures or osteomyelitic lesions.

Recent trials with selected patients have indicated that 99Tcm-tetrofosmin is a suitable agent for myocardial perfusion imaging. We performed 99Tcm-tetrofosmin perfusion imaging in an unselected group of 297 patients routinely referred to our department. Single photon emission tomographic (SPET) imaging was performed 45-60 min post-injection using a 2-day stress and rest protocol. Altogether, 192 patients were stressed on a treadmill and 105 using intravenous dobutamine. Comparison with angiography was possible in 86 patients, 65 of whom had atheromatous coronary artery disease and 21 of whom had normal coronary arteries (6 of whom fulfilled the criteria for syndrome X). The sensitivity for the detection of coronary artery disease was 94% (93% for exercise stress and 95% for dobutamine). The overall specificity was 85% (87% for exercise stress and 80% for dobutamine in the 15 normal patients and the segments supplied by disease-free coronary vessels in patients with disease elsewhere). We conclude that 99Tcm-tetrofosmin is a highly sensitive and specific agent for the detection of coronary artery disease, using both exercise and dobutamine stress, with few limitations.

Technetium-99m antimyosin (99mTc-AM) antibody imaging may have significant advantages over indium-111 antimyosin in clinical practice. The purpose of this study was to determine the human biodistribution, the safety profile and the sensitivity of 99mTc-AM (3-48) imaging in the detection of both Q-wave and non-Q-wave myocardial infarction (MI). Biodistribution and safety parameters were mainly determined in 12 normal healthy volunteers while 40 patients with proven MI (22 Q-wave, 18 non-Q-wave) were injected with 99mTc-AM (20-25 mCi) between 5 h and 7 days after the onset of acute chest pain. Three standard planar views were performed at 6 h and at 24 h post injection. Both sets of images were completed in 33 patients while two patients were imaged only at 6 h, three patients only at 18 h and one at 18 and 24 h. One patient was not imaged. Vital signs and ECG were recorded and blood samples for haematology, biochemistry and human antimurine antibodies (HAMA) and urinalysis were obtained in all volunteers and patients. No serious adverse reactions or side-effects attributable to 99mTc-AM have been reported. No volunteers or patients developed allergic reactions or significant increases in HAMA titres. Reading of 99mTc-AM imaging was performed by two blinded experienced observers. The sensitivity of 99mTc-AM in the detection of MI was 100% (21/21) for Q-wave and 83.3% (15/18) for non-Q-wave infarctions. The overall sensitivity was 92.3% (36/39). The three false-negative cases were inferoposterior MI. A certain degree of uptake focalization was seen in 26 out of 35 (74.2%) at 6 h. At 24 h, two patients (5.8%) did not show 99mTc-AM uptake while 22 (64.7%) showed intense focal uptake, seven (20.6%) moderate uptake and 3 (8.9%) slight uptake. It is concluded that 99mTc-AM (3-48) imaging is safe and shows high sensitivity in the detection of both Q-wave and non-Q-wave MI even with early imaging (6 h post injection). These promising results warrant further clinical investigation.

The platelet thrombogenicity of a hemodialyzer was quantified with 99mTc- and 111In-labeled platelets. The platelets collected from blood of Beagle dogs, Yorkshire pigs and human volunteers were labeled with 111In-tropolone (detergent-free) and 99mTc-HMPAO. Hemodialysis was performed with a hollow-fiber dialyzer (HFD) in a flow-loop, the temperature of which was maintained at 37 degrees C, with flow-rates of 7, 150 and 270 mL/min; after dialysis, the HFD radioactivity was measured with an ionization chamber and imaged with a gamma-camera. The radioactivity of samples of hollow-fibers taken from the top, middle and bottom of the dialyzer was determined with a gamma-counter. The mean values of hemodialyzer-adherent platelet radioactivity were calculated for both radionuclides. The canine platelets were found to be more thrombogenic than porcine and human platelets. The adhesivity of porcine platelets to the biomaterial (cellulose-acetate) of the dialyzer approximated that of human platelets. The 99mTc label underestimated the thrombus formation (P < 0.01). The dynamic processes of thrombosis and embolization from the hemodialyzer resulted in the large standard deviations around the mean values of the adherent thrombus. In spite of this limitation of the dynamic pathology, the quantitation of comparative thrombogenicity with 111In- and 99mTc-labeled platelets suggests that both radionuclides could be used for measurement of device-induced thrombogenicity and may provide an estimation of prosthesis-induced thrombogenicity of human platelets from animal studies.

Adverse reactions to radiopharmaceuticals are comparatively few in number. Various estimates quote an incident rate of 1 to 6 reactions per 100,000 injections. Other figures quoted are 1 in 800 for the bone-seeking radiopharmaceutical methylene diphosphonate, and 1 in 400 for the lung visualisation agent macroaggregated albumin. The very low numbers of reported adverse effects probably reflect the tiny amounts of material which are used in the formulation of radiopharmaceuticals. Adverse reactions to radiopharmaceuticals are usually mild and transient and require little or no medical treatment. A few reactions involve respiratory or circulatory collapse or loss of consciousness. Several fatalities have been reported with the liver scanning agent 99mTc (technetium 99m)-albumin colloid. Clinical manifestations may be categorised under the headings of vasomotor effects i.e. faintness, pallor, diaphoresis or hypotension, and anaphylactoid effects such as nausea, dermographism, wheezing, bronchospasm, erythema and pruritus. The most prominent group of radiopharmaceuticals that have been reported to produce adverse events are the diphosphonates, which are used for scanning the skeleton. Typical diphosphonate reactions include erythema (especially over the extremities), nausea, vomiting and malaise. The onset of reaction is usually 2 to 3 hours after injection. The second group of radiopharmaceuticals which give rise to adverse events are the colloids, which are used for liver and spleen scintigraphy. Typical colloid reactions include pallor, nausea, flush and pulse changes. Adverse events may also occur as a result of the patient's medication interfering with the disposition of the radiopharmaceutical. Although not usually hazardous or dangerous, such events may be so pronounced that a marked deviation in the expected pharmacokinetics may occur. Drug interactions can be conveniently categorised under the headings of unusual handling of the radiopharmaceutical because of pharmacological action, genuine in vivo interaction between the medication and radiopharmaceutical, drug-induced disease and interaction between the radiopharmaceutical and catheters or syringes. The most serious drug interactions are those where the patient is taking cortisone or cytotoxic agents prior to tumour scintigraphy. Other important effects occur in patients undergoing bone scanning who are receiving iron preparations. Nifedipine has been reported to produce quite severe problems in scanning, including difficulties in the radiolabelling of red cells (for cardiac scintigraphy), and other effects where the drug appears to prevent the transport of bone-seeking materials into the skeleton. Many drugs alter hormonal status and these effects may produce marked deviations from the expected biodistribution. Diethylstilbestrol (stilboestrol), digitalis, gonadotrophins, phenothiazines and cimetidine all increase estrogen levels in high doses.(ABSTRACT TRUNCATED AT 400 WORDS)

A novel 99mTc complex (1,2-bis[bis(2-ethoxyethyl)phosphino] ethane, 99mTc-tetrofosmin) has been developed to replace 201Tl in myocardial perfusion imaging. Biodistribution, safety and dosimetry of 99mTc-tetrofosmin were studied in 12 male volunteers, each at rest and during exercise. Safety parameters measured to 48 hr postinjection revealed no clinically significant long-term drug-related changes. Biodistribution was studied by acquiring whole-body or serial static images up to 48 hr postinjection. Technetium-99m-tetrofosmin shows good heart uptake (1.2%) with retention. Clearance is excellent from blood (< 5% by 10 min), liver (< 4.5% by 60 min) and lung. Sequestration of activity by skeletal muscle is enhanced during exercise. Radiation dosimetry calculations indicate that the effective dose, assuming a 3.5 hr bladder voiding period, is 32.9 x 10(-3) rad/mCi (8.9 x 10(-3) mSv/MBq) at rest and 26.7 x 10(-3) rad/mCi (7.1 x 10(-3) mSv/MBq) after exercise. Technetium-99m-tetrofosmin can produce high quality myocardial images from 5 min to several hours postinjection.

99mTc-Teboroxime [Chloro[tris(cyclohexyldioxime)methaneboronic acid] (99mTc)technetium], a perfusion agent for myocardial imaging, has a distinct advantage over 201Tl because of its very high myocardial extraction and is a 99mTc compound ideal for gamma camera imaging. This agent also demonstrates rapid myocardial washout, which allows completion of exercise and rest imaging studies in a short interval (to 1 hour). However, the rapid washout necessitates the completion of image acquisition very quickly after injection and therefore may require nonconventional SPECT imaging. In this Phase II study we evaluate the safety and efficacy of 99mTc-Teboroxime to detect coronary artery disease by exercise and rest SPECT imaging in 38 patients with prior myocardial infarction, 31 patients with angina pectoris, and 4 patients with non-coronary cardiac diseases. The 99mTc-Teboroxime dose used was 370-740 MBq in each study. The findings were compared with coronary angiography or 201Tl exercise and redistribution SPECT. No significant adverse reactions or laboratory abnormalities attributable to 99mTc-Teboroxime were observed. The quality of SPECT images was optimal in 62.5% of all patients. The relatively large population of suboptimal cases (37.5%) was attributed to the delay of the start and prolongation of the image acquisition time. In 85.7% of patients whose imaging was started within 5 minutes and completed within 11 minutes after injection, optimal quality was observed. Thus, 99mTc-Teboroxime SPECT requires the rapid completion of image acquisition after injection to achieve optimal image quality. Abnormalities of 99mTc-Teboroxime distribution were detected in 97.1% and 62.1% of patients with prior myocardial infarction or angina pectoris, respectively. The concordance with coronary angiography was 84.4% and 68.0%, and with 201Tl was 78.1% and 74.1%, respectively. Although standardization of the image protocol suitable for this agent is needed for the next study, these high correlations suggest the potential usefulness of 99mTc-Teboroxime SPECT imaging.

Adult patients undergoing nuclear medicine investigations may subsequently come into close contact with members of the public and hospital staff. In order to expand the available dosimetry and derive appropriate recommendations, dose rates were measured at 0.1, 0.5 and 1.0 m from 80 adult patients just before they left the nuclear medicine department after undergoing one of eight 99Tcm studies, an 123I thyroid, an 111In leucocyte or a 201Tl cardiac scan. The maximum departure dose rates at these distances of 150, 30 and 7.3 microSv h-1 were greater than those found in similar published studies of adult and paediatric patients. To limit the dose to an infant to less than 1 mSv, an 111In leucocyte scan is the only investigation for which it may be necessary to restrict close contact between the infant and a radioactive parent, depending on the dose rate near the surface of the patient, the parent's habits and how fretful is the infant. It is unlikely that a ward nurse will receive a dose of 60 microSv in a working day if caring for just one radioactive adult patient, unless the patient is classified as totally helpless and has undergone a 99Tcm marrow, bone or brain scan. The data and revised calculations of effective exposure times based on a total close contact time of 9 h in every 24 h period should allow worst case estimates of radiation dose to be made and recommendations to be formulated for other circumstances, including any future legislative changes in dose limits or derived levels.

In order to estimate the public radiation burden from nuclear medicine studies, a TLD chip in a sealed plastic bag was taped on the abdomen of patients who received 111In as chloride or oxine, 201T1 chloride, or one of four common 99mTc agents. The TLD chip was removed after 24 h. Additionally, abdominal skin surface exposure rate measurements were performed with an ionization chamber survey meter at various times (0 to about 60 h). There was superb correlation between TLD and integrated exposure rate measurements and between TLD and ionization chamber measurements and MIRD calculated doses. Scenarios postulated for exposure of co-workers and family members yielded doses between 7 muSv (0.7 mrem) and 20 muSv (2 mrem) for the selected radiopharmaceuticals. Calculations of the total population exposure from nuclear medicine procedures indicate the per capita dose (amortized over the entire population) is approximately 0.4 muSv (0.04 mrem), a negligible dose compared to natural background and total medical irradiation.