99mTc internal contaminations measurements among nuclear medicine medical personnel during ventilation - perfusion SPECT lung scans.

This paper presents results of measurements of 99mTc activity concentration in air and nuclear medical personnel blood during ventilation-perfusion SPECT lung scans. 99mTc activity measurements were conducted at the Nuclear Medicine Department, John Paul II Hospital, Krakow. Technicians and nurses who perform examinations were equipped with personal aspirators enabling air sampling to determine the radiation exposure at their workplaces. Measurements allowed to evaluate the concentration of 99mTc in 14 air samples and it ranged from 7800 ± 600 to 10,000 ± 1000 Bq m-3 for air samples collected by technicians and from 390 ± 30 to 600 ± 40 Bq m-3 for air samples collected by nurses. In addition 99mTc concentrations in blood of medical personnel were determined in 24 samples. For technicians the maximum 99mTc blood concentration levels reached 920 ± 70 Bq L-1 and 1300 ± 100 Bq L-1. In the case of nurses, the maximum estimated activity concentrations were about ten times lower, namely 71 ± 7 Bq L-1 and 39 ± 3 Bq L-1. Although the intakes appear to be relatively high, the resulting annual effective doses are about 34 µSv for technicians and only 2 µSv for nurses.

99mTc-CXCR4-L for Imaging of the Chemokine-4 Receptor Associated with Brain Tumor Invasiveness: Biokinetics, Radiation Dosimetry, and Proof of Concept in Humans.

Overexpression of the chemokine-4 receptor (CXCR4) in brain tumors is associated with high cancer cell invasiveness. Recently, we reported the preclinical evaluation of 99mTc-CXCR4-L (cyclo-D-Tyr-D-[NMe]Orn[EDDA-99mTc-6-hydrazinylnicotinyl]-Arg-NaI-Gly) as a SPECT radioligand capable of specifically detecting the CXCR4 protein. This research aimed to estimate the biokinetic behavior and radiation dosimetry of 99mTc-CXCR4-L in healthy subjects, as well as to correlate the radiotracer uptake by brain tumors in patients, with the histological grade of differentiation and CXCR4 expression evaluated by immunohistochemistry. 99mTc-CXCR4-L was obtained from freeze-dried kits prepared under GMP conditions (radiochemical purities >97%). Whole-body scans from six healthy volunteers were acquired at 0.3, 1, 2, 4, 6, and 24 h after 99mTc-CXCR4-L administration (0.37 GBq). Time-activity curves of different source organs were obtained from the image sequence to adjust the biokinetic models. The OLINDA/EXM code was employed to calculate the equivalent and effective radiation doses. Nine patients with evidence of brain tumor injury (6 primaries and 3 recurrent), determined by MRI, underwent cerebral SPECT at 3 h after administration of 99mTc-CXCR4-L (0.74 GBq). Data were expressed as a T/B (tumor uptake/background) ratio. Biopsy examinations included histological grading and anti-CXCR4 immunohistochemistry. Results showed a fast blood activity clearance (T 1/2 α = 0.81 min and T 1/2 ß = 12.19 min) with renal and hepatobiliary elimination. The average equivalent doses were 6.10E - 04, 1.41E - 04, and 3.13E - 05 mSv/MBq for the intestine, liver, and kidney, respectively. The effective dose was 3.92E - 03 mSv/MBq. SPECT was positive in 7/9 patients diagnosed as grade II oligodendroglioma (two patients), grade IV glioblastoma (two patients), grade IV gliosarcoma (one patient), metastasis, and diffuse astrocytoma with T/B ratios of 1.3, 2.3, 13, 7, 19, 5.5, and 3.9, respectively, all of them with positive immunohistochemistry. A direct relationship between the grade of differentiation and the expression of CXCR4 was found. The two negative SPECT studies showed negative immunohistochemistry with a diagnosis of reactive gliosis. This "proof-of-concept" research warrants further clinical studies to establish the usefulness of 99mTc-CXCR4-L in the diagnosis and prognosis of brain tumors.

Auto-immune Thyroiditis in an Infant Masquerading as Congenital Nephrotic Syndrome.

A seven-months-old girl under treatment for pneumonia presented with generalized edema, decreased urinary output and was found to have hypertension, muco-cutaneous fungal infection and pulmonary hypertension. Investigations revealed that she had heavy proteinuria, hypertriglyceridemia, hypoalbuminemia and elevated levels of free T3 and T4 with suppression of TSH levels in the serum. A diagnosis of autoimmune thyroiditis (AT) in thyrotoxic phase was made on the basis of clinical presentation and presence of anti-TPO antibodies and reduced uptake in thyroid (technetium) scintigraphy. The child responded to carbimazole therapy and propranolol. The case is presented to remind pediatricians about the rare occurrence of auto-immune thyroiditis in infancy with rare complications such as nephrotic syndrome and pulmonary hypertension.

Synthesis of 99m Tc-roxithromycin: A novel diagnostic agent to discriminate between septic and aseptic inflammation.

Roxithromycin is a second-generation macrolide antibiotic derived from erythromycin. In the current study, roxithromycin (ROX) was successfully labeled with technetium-99m for early diagnosis of bacterial infection and discrimination between septic and aseptic inflammation. The highest radiochemical purity of ≥95% was achieved by investigating different labeling parameters such as pH, ligand/reducing agent concentration, temperature, and amount of stabilizing agent. For this purpose, 0.3-0.5 mg ligand, 2-6 µg SnCl2 ·2H2 O as a reducing agent at basic pH (8-10 pH) and 2 mg mannitol used as a stabilizing agent, in the end, 370 MBq 99m Tc added into the reaction vials and incubated for a wide range of temperature (-4 to 65°C). The percent radiochemical purity of 99m Tc-roxithromycin was assessed with the help of the radio-thin-layer chromatography technique. The characterization studies were carried out using electrophoresis and Radio-HPLC techniques as well as saline stability and serum stability studies were also performed. Furthermore, biodistribution study was also performed in an inflamed animal model to discriminate between septic (heat-killed Staphylococcus aureus) and aseptic (turpentine oil) inflammatory lesions. The results were elaborated that 99m Tc-roxithromycin (99m Tc-ROX) was clearly bounded at the septic inflammation site (T/NT ratio of 7.08 ± 1.14) at 30 min postadministration, and maximum accumulation was seen in heart, lungs, liver, stomach, kidneys, and intestine. The results were suggested that 99m Tc-ROX might be used to discriminate between septic and aseptic inflammatory lesions at an early stage.

Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans.

BACKGROUND: Candida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99mTc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection. METHODS: Fluconazole was radiolabeled with technetium-99 metastable (99mTc) and encapsulated into conventional (99mTc-Fluconazole-PLA-POLOX) and surface-modified (99mTc-Fluconazole-PLA-PEG) NCs by the interfacial deposition of the preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by solvent evaporation. The size distribution and zeta potential of the NCs preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. Free and encapsulated 99mTc-fluconazole were administered intravenously in immunosuppressed mice bearing a local infection induced by Candida Albicans inoculation in the right thigh muscle. At pre-established time intervals, tissues and organs of interest were removed and radioactivity was measured in an automatic gamma radiation counter. RESULTS: The NCs diameter was between 200 and 400 nm with negative zeta potential values. Free 99mTc-fluconazole was more rapidly eliminated by the renal system compared to the encapsulated drug in NCs, which remained longer in blood circulation. The uptake of conventional NCs by mononuclear phagocyte system organs was higher than the one demonstrated by the surface-modified NCs. Both NCs remained longer in the infectious focus when compared to free 99mTc-fluconazole, but the results did not show a significant difference between NC formulations. CONCLUSION: These data indicate that these NCs might represent a therapeutic alternative for the treatment of candidiasis, once they remain more time in the infectious focus, allowing high retention of 99mTc-fluconazole at this site.

Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study.

A range of antitumor agents for cancer treatment is available; however, they show low specificity, which often limit their use. Recently, we have reported the preparation of folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX) loaded with paclitaxel (PTX), an effective drug for the treatment of solid tumors, including breast cancer. The purpose of this study was to prepare and characterize SpHL-PTX and SpHL-folate-PTX radiolabeled with technetium-99m (99mTc). Biodistribution studies and scintigraphic images were performed after intravenous administration of 99mTc-PTX, 99mTc-SpHL-PTX and 99mTc-SpHL-folate-PTX into healthy and tumor-bearing mice. High radiochemical purity (>98%) and in vitro stability (>90%) were achieved for both liposome formulations. The pharmacokinetic properties of 99mTc-SpHL-DTPA-PTX and 99mTc-SpHL-folate-DTPA-PTX decreased in a monophasic manner showing half-life of 400.1 and 541.8min, respectively. Scintigraphic images and biodistribution studies showed a significant uptake in liver, spleen and kidneys, demonstrating these routes as way for excretion. At 8h post-injection, the liposomal tumor uptake was higher than 99mTc-PTX. Interesting, 4h after administration, the liposome folate coated showed higher tumor-to-muscle ratio than 99mTc-SpHL-DTPA-PTX and 99mTc-PTX. In conclusion, the liposomal systems, showed high tumor uptake by scintigraphic images, especially the 99mTc-SpHL-folate-DTPA-PTX that showed a sustained and higher tumor-to-muscle ratio than non-functionalized liposome, which indicate its feasibility as a PTX delivery system to folate positive tumors.

Human Fibronectin Extra-Domain B (EDB)-Specific Aptide (APTEDB) Radiolabelling with Technetium-99m as a Potent Targeted Tumour-Imaging Agent.

BACKGROUND: Human fibronectin extra-domain B (EDB) is particularly expressed during angiogenesis progression. It is, thus, a promising marker of tumour growth. Aptides are a novel class of peptides with high-affinity binding to specific protein targets. APTEDB is an antagonist-like ligand that especially interacts with human fibronectin EDB. OBJECTIVE: This study was the first attempt in which the hydrazinonicotinamide (HYNIC)-conjugated APTEDB was labelled with technetium-99m (99mTc) as an appropriate radiotracer and tricine/EDDA exchange labeling. METHODS: Radiochemical purity, normal saline, and serum stability were evaluated by HPLC and radio-isotope TLC scanner. Other examinations, such as protein-binding calculation, dissociation radioligand binding assay, and partition coefficient constant determination, were also carried out. The cellular-specific binding of 99mTc- HYNIC-conjugated APTEDB was assessed in two EDB-positive (U87MG) and EDB-negative (U373MG) cell lines. Bio-distribution was investigated in normal mice as well as in U87MG and U373MG tumour-bearing mice. Eventually, the radiolabelled APTEDB was used for tumour imaging using planar SPECT. RESULTS: Radiolabelling was achieved with high purity (up to 97%) and accompanied by high solution (over 90% after overnight) and serum (80% after 2 hours) stability. The obtained cellular-specific binding ratio was greater than nine-fold. In-vivo experiments showed rapid blood clearance with mainly renal excretion and tumour uptake specificity (0.48±0.03% ID/g after 1h). The results of the imaging also confirmed considerable tumour uptake for EDB-positive cell line compared with the EDB-negative one. CONCLUSION: Aptides are considered to be a potent candidate for biopharmaceutical applications. They can be modified with imaging or therapeutic agents. This report shows the capability of 99mTc-HYNIC-APTEDB for human EDB-expressing tumours detection.

Detection of bacterial infection by a technetium-99m-labeled peptidoglycan aptamer.

Nuclear medicine clinicians are still waiting for the optimal scintigraphic imaging agents capable of distinguishing between infection and inflammation, and between fungal and bacterial infections. Aptamers have several properties that make them suitable for molecular imaging. In the present study, a peptidoglycan aptamer (Antibac1) was labeled with 99mTc and evaluated by biodistribution studies and scintigraphic imaging in infection-bearing mice. Labeling with 99mTc was performed by the direct method and the complex stability was evaluated in saline, plasma and in the molar excess of cysteine. The biodistribution and scintigraphic imaging studies with the 99mTc-Antibac1 were carried out in two different experimental infection models: Bacterial-infected mice (S. aureus) and fungal-infected mice (C. albicans). A 99mTc radiolabeled library, consisting of oligonucleotides with random sequences, was used as a control for both models. Radiolabeling yields were superior to 90% and 99mTc-Antibac1 was highly stable in presence of saline, plasma, and cysteine up to 6h. Scintigraphic images of S. aureus infected mice at 1.5 and 3.0h after 99mTc-Antibac1 injection showed target to non-target ratios of 4.7±0.9 and 4.6±0.1, respectively. These values were statistically higher than those achieved for the 99mTc-library at the same time frames (1.6±0.4 and 1.7±0.4, respectively). Noteworthy, 99mTc-Antibac1 and 99mTc-library showed similar low target to non-target ratios in the fungal-infected model: 2.0±0.3 and 2.0±0.6for 99mTc-Antibac1 and 2.1±0.3 and 1.9 ± 0.6 for 99mTc-library, at the same times. These findings suggest that the 99mTc-Antibac1 is a feasible imaging probe to identify a bacterial infection focus. In addition, this radiolabeled aptamer seems to be suitable in distinguishing between bacterial and fungal infection.

Synthesis of 99mTc-Rifabutin: A Potential Tuberculosis Radiodiagnostic Agent.

BACKGROUND: Rifabutin (RFN) is bactericidal antibiotic with a very broad spectrum of activity against gram positive & gram negative organisms including Pseudomonas aeruginosa and specifically Mycobacterium tuberculosis. RFN inhibits DNA dependent RNA polymerase activity in susceptible cells. In the instant work, the therapeutic characteristics of RFN were intended for diagnostic rationale by labeling it with 99mTc (Technetium-99m). OBJECTIVE: The 99mTc labeled RFN (99mTc-RFN) was investigated for labeling capacity, steadiness in saline & serum, in vitro Mycobacterium tuberculosis (MBT) uptake & distribution in MBT stained animal model rats. METHOD: It was found that 99mTc-RFN prepared by mixing 2 mg of RFN, 2.5 mCi sodium pertechnetate, 150 µg stannous chloride at pH 5.4 gave highest yield after 30 minutes and was intact above 90 % after 240 min at room temperature in saline. RESULT: The 99mTc-RFN showed a stable profile in serum at 37 °C and impurities appeared up 16 h was 15.20 %. The maximum in vitro MBT uptake observed in live strain was 71.75 ± 0.75 %. The premier uptake observed in the MBT infected site (target site) was 14.15 ± 0.00 %, in animal model rat. CONCLUSION: Higher labeling capacity, steadiness in saline & serum, higher MBT uptake, maximum uptake in the MBT infected sites and precise imaging posed 99mTc- RFN as an alternate radio-drug for tuberculosis scintigraphy.

Automatic in-syringe dispersive liquid-liquid microextraction of 99Tc from biological samples and hospital residues prior to liquid scintillation counting.

A new approach exploiting in-syringe dispersive liquid-liquid microextraction (DLLME) for (99)Tc extraction and preconcentration from biological samples, i.e., urine and saliva, and liquid residues from treated patients is presented. (99)Tc is a beta emitter with a long half-life (2.111 × 10(5) years) and mobility in the different environmental compartments. One of the sources of this radionuclide is through the use of its father (99m)Tc in medical diagnosis. For the first time a critical comparison between extractants and disperser solvents for (99)Tc DLLME is presented, e.g., tributyl phosphate (TBP), trioctylmethylammonium chloride (Aliquat®336), triisooctylamine (TiOA), as extractants in apolar solvents such as xylene and dodecane, and disperser solvents such as acetone, acetonitrile, ethanol, methanol, 1-propanol, and 2-propanol. The system was optimized by experimental design, and 22.5% of Aliquat®336 in acetone was selected as extractant and disperser, respectively. Off-line detection was performed using a liquid scintillation counter. The present method has a (99)Tc minimum detectable activity (MDA) of 0.075 Bq with a high extraction/preconcentration frequency (8 h(-1)). Urine, saliva, and hospital residues were satisfactorily analyzed with recoveries of 82-119%. Thus, the proposed system is an automatic powerful tool to monitor the entry of (99)Tc into the environment. Graphical Abstract (99m)Tc is widely used in Nuclear Medicine for diagnosis. Its daugther (99)Tc is automatically monitored in biological samples from treated patients by in-syringe dispersive liquid-liquid microextraction.

Development of a freeze-dried kit formulation for the preparation of 99mTc-NTP 15-5, a radiotracer for scintigraphic imaging of proteoglycans.

The cartilage-targeting strategy is based on the strong affinity of quaternary ammonium (QA) functions for cartilage proteoglycans. We use a bifunctional agent containing QA moiety and a polyazamacrocycle structure able to complex technetium-99m. (99m)Tc-NTP 15-5 was selected for its high stability and its high affinity for proteoglycans in vivo. Labeling conditions of NTP 15-5 were optimized, and a lyophilized kit was developed for radiolabeling of (99m)Tc-NTP 15-5 (radiochemical yields 94.6±1.8%). (99m)Tc-NTP 15-5 was stable and resulted in favorable biological evaluations.

99mTc-labeled vasopressin peptide as a radiopharmaceutical for small-cell lung cancer (SCLC) diagnosis.

The 99mTc-labeled conjugates of the vasopressin (AVP) peptide and of its analogue d(CH2)5[D-Tyr(Et2)-Ile4-Eda9]AVP (AVP(an)) have been synthesized using the technetium complexes with tetradentate tripodal chelator (the tris(2-mercaptoethyl)amine (NS3)) and the monodentate isocyanide ligand (CN-peptide). The conjugates exhibit high stability in the presence of 100 times the molar excess of standard amino acids cysteine or histidine and also satisfactory stability in human serum. The 99mTc(NS3)(CN-AVP) and 99mTc(NS3)(CN-AVP(an)) ability of binding to small-cell lung cancer (SCLC) cell line H69 was studied in vitro. The results suggest that the novel vasopressin conjugate 99mTc(NS3)(CN-AVP(an)) is a desirable compound for imaging oncogene receptors overexpressed in SCLC cells and can be an important basis for further consideration the conjugate as a potential diagnostic radiopharmaceutical for patients suffering from small-cell lung cancer.

Radiolabeling of cisplatin and its biodistribution in an experimental model of lung carcinogenesis.

This study optimized the radiolabeling of cisplatin with technetium-99m (99mTc) and evaluated its biodistribution in an experimental model of lung carcinogenesis. The percentage labeling of cisplatin with 99mTc was assessed using an ascending chromatographic technique. For biodistribution studies, male rats were divided into 2 groups. The control group received normal saline intratracheally, whereas the treatment group received intratracheal administration of carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) at a dose of 20 mg/kg body weight. The resulting radiopharmaceutical (99mTc-cisplatin) showed 98% labeling efficiency and was found to be stable for up to 6 hours both in both serum and saline under normal conditions. The blood clearance of the 99mTc-cisplatin followed a biphasic release pattern whereby a fast-release phase was observed at 35 seconds and a slow-release phase was observed after 30 minutes of drug administration. The biodistribution studies of control and treated animals revealed high uptake of 99mTc-cisplatin by the liver and slow excretion via the kidneys. However, a time-dependent increase in the lung-to-muscle specific uptake ratio was observed in DMBA-treated rats. The study concluded that 99mTc-cisplatin possesses selectivity toward cancerous lung tissue and can be explored further for its diagnostic potential in the detection of lung cancer and the evaluation of treatment response.

Biodistribution of amikacin solid lipid nanoparticles after pulmonary delivery.

The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration in the lungs for treatment of cystic fibrosis lung infections and also providing a new method for clinical application of amikacin. To achieve this aim, (99m)Tc labelled amikacin was loaded in cholesterol SLNs and after in vitro optimization, the desired SLNs and free drug were administered through pulmonary and i.v. routes to male rats and qualitative and biodistribution studies were done. Results showed that pulmonary delivery of SLNs of amikacin by microsprayer caused higher drug concentration in lungs than kidneys while i.v. administration of free drug caused reverse conditions. It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs.

Determination of isoniazid concentration in rabbit vertebrae by isotope tracing technique in conjunction with HPLC.

Medications compounded with isoniazid (INH) are usually applied to surgical sites at the completion of surgery to locally kill postoperative residual tubercle bacilli. However, the distribution and elimination of INH in the vertebrae in vivo are not known. In this study, isotope tracing was used in conjunction with high-pressure liquid chromatography (HPLC) to address this. INH and technetium-99 m-labeled INH were applied to the vertebrae of rabbits. After 2 and 6 h, osseous tissues containing INH, as determined by radionuclide imaging, were collected for detection with HPLC. The results showed that INH mainly stayed around the vertebrae 6 h after its application and did not permeate widely into the blood or other organs, except for the kidneys. The standard deviations of INH concentrations in the technetium-99 m-INH group were approximately four-fold smaller than those in the INH group. This method of coupling isotope tracing and HPLC can effectively limit experimental error during sample collection, allowing accurate and reliable identification of the concentration levels of INH in osseous tissues in vivo.

Design, synthesis, and biological evaluation of catecholamine vehicle for studying dopaminergic system.

Catecholamine mimetic EDTA-bis(tyramide) was synthesized and characterized by various spectroscopic techniques (NMR, mass spectroscopy) and λem 310 nm for the excitation at 270 nm. Molecular docking studies were performed with human serum albumin (PDB 1E78), showing binding pattern with amino acid residues Arg218, Arg222, and Lys444, identifies the ligand-human serum albumin interaction for the transportation affinity of the ligand at the specific site of the target. Subsequently, binding study with human serum albumin at λex  = 350 nm found to be 5.847 × 10(4)  m(-1) shows effective quenching effect. Additionally, to go more insight, acetylcholinesterase binding affinity was investigated, which shows 90% binding affinity for the 10 mm concentration. IC50 value was found 18.60 µm for MAO-B inhibition. Finally, EDTA-bis(tyramide) labeled with (99m) Tc to investigate its in vivo radiopharmaceutical efficiency having 97% binding affinity with 98% radiochemical purity. In vivo studies were carried out for (99m) Tc-EDTA-bis(tyramide) included blood kinetics showed a quick wash out from the circulation via renal route, and biodistribution revealed that maximum %ID/g was found in kidney at 1 h, and its scintigraphy image shows 3.96% brain uptake with respect to whole body.

Quantitative assessment of altered rectal mucosal permeability due to rectally applied nonoxynol-9, biopsy, and simulated intercourse.

BACKGROUND: Microbicide toxicity may reduce the efficacy of topical preexposure prophylaxis for human immunodeficiency virus (HIV) transmission. Noninvasive quantitative measures of microbicide toxicity would usefully inform microbicide development. METHODS: Ten subjects received 3 one-time interventions: 5 mL of Normosol-R fluid alone (negative control), 5 mL of 2% nonoxynol-9 (N-9) gel, and 5 mL of Normosol-R with coital simulation and sigmoidoscopic biopsy (CS + BX). Each dose of N-9 and Normosol-R contained 500 µCi of (99m)technetium-diethylene triamine pentaacetic acid. Plasma and urine radioactivity was assessed over 24 hours. RESULTS: The plasma radioisotope concentration peaked 1 hour after N-9 dosing. The mean maximum radioisotope concentration after N-9 receipt was 12.0 times (95% confidence interval [CI], 6.8-21.0) and 8.4 times (95% CI, 5.2-13.5) the mean concentration after Normosol-R control receipt and CS + BX receipt, respectively; paired differences persisted for 24 hours. After N-9 dosing, the urine isotope level was 3.6 times (95% CI, 1.1-11.4) the level observed 8 hours after Normosol-R control receipt and 4.0 times (95% CI, 1.4-11.4) the level observed 4 hours after CS + BX receipt. Permeability after CS + BX receipt was greater than that after Normosol-R control receipt in 0-2-hour urine specimens only (mean permeability, 2.4; 95% CI, 1.0-5.8) but was not greater in blood. CONCLUSIONS: Plasma sampling after rectal radioisotope administration provided quantitative estimates of altered mucosal permeability after chemical and mechanical stresses. Permeability testing may provide a useful noninvasive adjunct to assess the mucosal effects of candidate microbicides. Clinical Trials Registration. NCT00389311.

Preparation and preliminary biological evaluation of novel (99m)Tc-labelled thymidine analogs as tumor imaging agents.

Two kinds of novel thymidine derivatives, N-thymidine-yl-N'-methyl-N'-{N''-[2-sulfanyl-(ethylamino)acetyl]-2-aminoethylsulfanyl-1-hexanamide}-ethanediamine (TMHEA) and N-thymidine-yl-N'-methyl-N'-{N''-[2-sulfanyl-(ethylamino)acetyl]-2-aminoethylsulfanyl-1-hexanamide}-hexanediamine (TMHHA) were prepared and successfully labeled with (99m)Tc in high labeling yields. The in vitro stability and in vivo biodistribution of (99m)Tc-TMHEA and (99m)Tc-TMHHA were investigated and compared. The biodistribution studies indicate that the radiotracer (99m)Tc-TMHEA displays selective tumor uptake, suggesting it is a potential tumor imaging agent.

Evaluating abdominal oedema during experimental sepsis using an isotope technique.

PURPOSE: Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients. PROCEDURES: We modified a double-isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin-exposed ('septic') piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium-99m ((99m)Tc) and Transferrin labelled with Indium111 ((111)In). Images were acquired on a dual-head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique. RESULTS: No (99m)Tc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, (111)In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4·06 times higher in the LPS group compared to the healthy controls (P<0·0001). Abdominal free fluid, studied in 3 animals, had as high (111)In activity as in plasma, but no (99m)Tc activity. Intestinal lymphatic vessel size was higher in LPS (3·7 ± 1·1 µm) compared to control animals (0·6 + 0·2 µm; P<0·001) and oedema correlated to villus diameter (R(2) = 0·918) and lymphatic diameter (R(2) = 0·758). A correlation between a normalized index of oedema formation (NI) and intra-abdominal pressure (IAP) was also found: NI = 0·46*IAP-3·3 (R(2) = 0·56). CONCLUSIONS: The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic.

Structural modifications of 99mTc-labelled bombesin-like peptides for optimizing pharmacokinetics in prostate tumor targeting.

PURPOSE: The main goal of the present study was to investigate the importance of the addition of a positively charged aa in the naturally occurring bombesin (BN) peptide for its utilization as radiodiagnostic agent, taking into consideration the biodistribution profile, the pharmacokinetic characteristics and the tumor targeting ability. METHODS: Two BN-derivatives of the general structure [M-chelator]-(spacer)-BN(2-14)-NH(2), where M: (99m)Tc or (185/187)Re, chelator: Gly-Gly-Cys-, spacer: -(arginine)(3)-, M-BN-A; spacer: -(ornithine)(3)-, M-BN-O; have been prepared and evaluated as tumor imaging agents. RESULTS: The peptides under study presented high radiolabelling efficiency (>98%), significant stability in human plasma (>60% intact radiolabelled peptide after 1h incubation) and comparable receptor binding affinity with the standard [(125)I-Tyr(4)]-BN. Their internalization rates in the prostate cancer PC-3 cells differed, although the amount of internalized peptide was the same. The biodistribution and the dynamic γ-camera imaging studies in normal and PC-3 tumor-bearing SCID mice have shown significant tumor uptake, combined with fast blood clearance, through the urinary pathway. CONCLUSION: The addition of the charged aa spacer in the BN structure was advantageous for biodistribution, pharmacokinetics and tumor targeting ability, because it reduced the upper abdominal radioactivity levels and increased tumor/normal tissue contrast ratios.