Semi-quantification of renal perfusion using 99mTc-DTPA in systolic heart failure: a feasibility study.

BACKGROUND: Renal scintigraphy with 99mTc-diethylenetriaminepentaacetic acid (DTPA) may be used to study renal perfusion (RP) in heart failure (HF) patients. The goal of this study was to establish a new method to assess RP in patients with systolic HF. METHODS: In this retrospective, single-center, observational study, 86 subjects with left ventricular ejection fraction ≤ 45% and 31 age-matched subjects without HF underwent renal scintigraphy with 99mTc-DTPA. Patients with HF were classified into two categories according to the New York Heart Association (NYHA) functional class, i.e., moderate HF with NYHA functional class I or II and severe HF with NYHA functional class III or IV. The first-pass time-activity curve of the renal scintigraph was recorded. The GFR was determined by Gates' method. The time to peak perfusion activity (Tp), the slope of the perfusion phase (Sp), the slope of the washout phase (Sw), and glomerular filtration rate (GFR) in the study were obtained. Differences between groups were assessed by one-way analysis of variance with the Bonferroni post hoc test and rank-sum test. RESULTS: RP in HF was impaired despite comparable GFRs between the control and HF groups. RP in HF was characterized by a longer Tp and a shallower Sp and Sw. The primary parameter (Tp) was significantly prolonged in patients with HF (41.63 ± 12.22 s in severe HF vs. 26.95 ± 6.26 s in moderate HF vs. 17.84 ± 3.17 s in control, P < 0.001). At a cutoff point of 22 s, there was a high sensitivity (0.895) and specificity (0.935) in identifying patients with HF. CONCLUSIONS: Renal scintigraphy with 99mTc-DTPA may represent a new and useful method to noninvasively monitor RP abnormalities in HF.

Cy3-tilmanocept labeling of macrophages in joints of mice with antibody-induced arthritis and synovium of human patients with rheumatoid arthritis.

γ-Tilmanocept (99m Tc-tilmanocept) is a receptor-directed, radiolabeled tracer that is FDA-approved for guiding sentinel lymph node biopsy. Tilmanocept binds the C-type lectin mannose receptor (MR, CD206) on macrophages. In this study, nonradioactive, fluorescently-labeled Cy3-tilmanocept was used to detect CD206+ mononuclear cells in the cartilage of mice with antibody-induced arthritis and in the synovial fluid and tissue of human subjects with rheumatoid arthritis (RA) for comparison with osteoarthritis (OA), and healthy volunteer (HV) controls. Murine arthritis was induced by injection of monoclonal anti-cartilage antibody followed by injection of Escherichia coli lipopolysaccharide. Post-arthritis development (7-11 days), the mice were injected intravenously with Cy3-tilmanocept followed by in vivo and ex vivo epifluorescence imaging. Two-photon imaging, immunofluorescence, and immunohistochemistry were used to identify articular and synovial macrophages (CD206, F4/80, and Cy3-tilmanocept binding) in murine tissues. Cy3-tilmanocept epifluorescence was present in arthritic knees and elbows of murine tissues; no radiographic changes were noted in the skeletons. However, inflammatory arthritic changes were apparent by histopathology and immunohistochemistry (F4/80), immunofluorescence (CD206) and Cy3-tilmanocept binding. In human RA synovial fluid, Cy3-tilmanocept staining correlated with CD206+ /CD16+ cells; negligible labeling was observed in OA samples. Cy3-tilmanocept colocalized with CD206 and staining was significantly higher in RA synovial tissue compared to OA or HV. Our results demonstrate that imaging with Cy3-tilmanocept can detect in vivo inflammatory, CD206+ macrophages in an early arthritis animal model and in human RA patients. These data establish a novel tool for preclinical research of early arthritis and have implications for early RA detection and monitoring of therapeutic efficacy in humans.

The Application of 99mTc-DTPA Renal Dynamic Imaging to Measuring Renal Function of Children with Acute Lymphoblastic Leukemia after Induction Therapy.

PURPOSE: The study was aimed at assessing renal functions of children with acute lymphoblastic leukemia (ALL) after induction therapy by 99mTc-DTPA renal dynamic imaging Gates method (GFRGates) and investigating whether renal function after induction therapy will affect the occurrence of high-dose methotrexate- (HDMTX-) induced acute kidney injury (AKI). METHODS: Children with newly diagnosed ALL were enrolled. Renal functions before the administration of HDMTX were assessed by estimated glomerular filtration rate (eGFR) and GFRGates, respectively, before the first cycle of HDMTX after induction therapy. The areas under the ROC curve were used to assess covariates' ability to predict HDMTX-induced AKI. RESULTS: 102 children with ALL were included in the study. A stepwise backward binary logistic regression showed that only standardized GFRGates was an independent risk factor for HDMTX-induced AKI (p = 0.018, odds ratio 0.985, 95% CI 0.972-0.997). The area under the ROC of standardized GFRGates was 0.679 (p = 0.012, 95% CI 0.554-0.804). CONCLUSION: Standardized GFRGates showed that the normal renal function of children is not enough to be used as a cutoff point to predict HDMTX-induced AKI in ALL children receiving HDMTX. More attention and supportive care should be given to the children with standardized GFRGates lower than the cutoff value to avoid the HDMTX-induced AKI.

The features of technetium-99m-DTPA renal dynamic imaging after severe unilateral ureteral obstruction in adult rabbits.

BACKGROUND: It is controversial to evaluate the function of hydronephrotic kidneys by renal dynamic imaging (RDI). Our aim was to study the features of renal dynamic imaging (RDI) at different stages after unilateral ureteral obstruction (UUO) and to investigate a method that could be reasonably used to evaluate renal function and predict renal functional recoverability. METHODS: We made UUO models using fifteen adult New Zealand white rabbits and systematically observed the changes in kidney morphology, blood flow, radiotracer distribution and function by RDI. We then compared the differences in terms of imaging features between different periods and analyzed the relationship between blood flow and function in obstructed kidneys. RESULTS: 1) Obstructed kidneys gradually became larger than preoperative kidneys and contralateral kidneys (P<0.05) and reached their peak size between days 42 and 56, after which they gradually got smaller in size. 2)The correlation between the blood perfusion of the obstructed kidney and the obstruction duration (r = 0.125, P = 0.045) was very weak. In the initial period of obstruction, the perfusion of the obstructed kidney significantly decreased, followed by a sharp rebound in later days, and then the perfusion declined again. The peak in blood perfusion was on day 7. 3) The uptake rate of the obstructed kidney drastically decreased in the early stage and became lower than that of the contralateral kidney and the kidney before the operation (P<0.05), after which uptake increased gradually; the peak was on day 28. After that, uptake gradually decreased. 4) The grading of the radiotracer distribution in obstructed kidneys was positively correlated with the obstruction duration (r = 0.975, P = 0.000), and a uniform renal distribution was an early feature of obstruction. 5) The blood perfusion of the obstructed kidney and its functioning frequently increased or decreased simultaneously, but sometimes there was also a mismatch. The peak of renal blood perfusion recovery occurred prior to the peak of renal function recovery. CONCLUSION: In different periods of severe UUO, the imaged features of obstructed kidneys were different. These features are beneficial for determining the degree of hydronephrosis and renal function and predicting renal functional recoverability.

The displacement study of 99m Tc-DTPA-Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking.

The 99m Tc-DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used in renal scintigraphy. The human serum albumin (HSA) binding site(s) for the 99m Tc-DTPA have never been characterized. This study will cover in vitro the binding rates of 99m Tc-DTPA on HSA and the 99m Tc-DTPA competition interactions with two drugs having known human serum albumin binding sites. Furosemide (FUR) and metformin (MET) were added to 99m Tc-DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99m Tc-DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods. The 99m Tc-DTPA binding rates to human serum albumin increased with the highest concentration. Both drugs FUR and MET displaced 99m Tc-DTPA binding. 99m Tc-DTPA could bind to human serum albumin in many locations in site I and I-II, but strongly bound to site I through hydrogen bonds.

Prospective comparison between DCE-MRR and 99m Tc-DTPA-based SPECT for determination of allograft renal function.

BACKGROUND: Glomerular filtration rate (GFR) is a preferred indicator of allograft renal function, but direct measurement of GFR remains complicated. PURPOSE: To prospectively compare dynamic contrast-enhanced MR renography (DCE-MRR) with 99m Tc-DTPA-based single-photon emission computed tomography (SPECT) for determination of allograft renal function. STUDY TYPE: Prospective. POPULATION: Seventy kidney-transplant recipients FIELD STRENGTH: A low-dose DCE-MRR with a 3.0T scanner and a 99m Tc-DTPA-based SPECT after renal transplantation were performed. ASSESSMENT: A Baumann-Rudin (BR) and a modified two-compartment model (JZ2C) were used for DCE-MRR analysis. Standard Gate's method was used for SPECT analysis. An endogenous creatinine clearance rate (CCr) constituted the reference standard. STATISTICAL TESTS: Pearson correlation test and Bland-Altman agreement analysis. RESULTS: The reference CCr-GFR was 59.58 ± 23.72 mL/min/1.73 m2 . GFR determined by eGFR, BR, JZ2C, and SPECT was 90.22 ± 34.38, 36.78 ± 14.46, 48.99 ± 23.88, and 67.32 ± 18.44 mL/min/1.73 m2 , respectively. DCE-MRR using JZ2C had the best overall performance, with a Pearson correlation coefficient of 0.81, a bias of -10.58 mL/min/1.73 m2 , and a precision of 14.61 mL/min/1.73 m2 , as well as high accuracy (30-50% intervals: 74.3-90.0%). Although SPECT had a small bias (7.74 mL/min/1.73 m2 ), it had a poor correlation coefficient (0.38), poor precision (23.93 mL/min/1.73 m2 ), and low accuracy (64.3-72.3%) as compared with DCE-MRR using JZ2C. DATA CONCLUSION: DCE-MRR using JZ2C is superior to 99m Tc-DTPA-based SPECT to determine allograft renal function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:262-269.

The synthesis of a new macromolecule for the sentinel node detection: 99mTc-gly-mannosyl-dextran.

OBJECTIVE: We aimed to design and synthesize a new macromolecule for sentinel node detection to improve the imaging quality and avoid possible adverse effect. BACKGROUND: The imaging of sentinel lymph node has been an important field in the nuclear medicine. A lot of imaging agents have been developed, including Tc-sulfer colloid, Tc-labeled dextrans and the latest Tc-DTPA-mannosyl-dextran. With the technology advanced, the imaging ability of the agents has been better and better. However, there are still some drawbacks. MATERIALS AND METHODS: The new macromolecule agent was based on the dextran macromolecule backbone. Then the gly-gly-gly and mannose molecules were conjugated onto the backbone proportionally by targeting two different reaction sites. Once the new macromolecule was labelled with Tc, its imaging ability was tested by single-photon emission computed tomography scanning with Tc-sulfur colloid as the comparison. RESULTS: The average numbers of gly-gyl-gyl and mannosyl groups on the dextran backbone are determined to be ∼1: 2 per dextran. The average molecular diameter and molecular weight are measured to be 5.4±0.7 nm and 10 324 g/mol, respectively. The macromolecule is labelled by Tc with 93.2±2.4% radiochemical yield. The lymphatic imaging by single-photon emission computed tomography with the labeled compound showed no worse imaging ability but cost less time than the commercially available Tc-sulfur colloid. CONCLUSION: A new macromolecule imaging agent for sentinel node detection has been synthesized with better imaging ability and less imaging time cost.

99m Tc-labeled DTPA-colchicine dimer with improved tumor uptake.

This work reports the synthesis, radiolabeling, and biological studies of 99m Tc-diethylene triamine pentaacetic acid (DTPA)-colchicine dimer in tumor-bearing mice. The novel colchicine dimer was successfully synthesized by conjugation of DTPA to 2 colchicine biomolecules. The ligand could be labeled by 99m Tc in high yield to get 99m Tc-DTPA-colchicine dimer, which was hydrophilic and stable at room temperature. Biodistribution and imaging studies in tumor-bearing mice showed that 99m Tc-DTPA-colchicine dimer accumulated in the tumor with improved uptake and retention. The results indicate the need for synthetic modification of the parent colchicine derivative and the 99m Tc-chelate with a view to improve the tumor-targeting efficacy and in vivo kinetic profiles.

Decorated Superparamagnetic Iron Oxide Nanoparticles with Monoclonal Antibody and Diethylene-Triamine-Pentaacetic Acid Labeled with Thechnetium-99m and Galium-68 for Breast Cancer Imaging.

PURPOSE: In this study we developed and tested an iron oxide nanoparticle conjugated with DTPA and Trastuzumab, which can efficiently be radiolabeled with 99m-Tc and Ga-68, generating a nanoradiopharmaceutical agent to be used for SPECT and PET imaging. METHODS: The production of iron oxide nanoparticle conjugated with DTPA and Trastuzumab was made using phosphorylethanolamine (PEA) surface modification. Both radiolabeling process was made by the direct radiolabeling of the nanoparticles. The in vivo assay was done in female Balb/c nude mice xenografted with breast cancer. Also a planar imaging using the radiolabeled nanoparticle was performed. RESULTS: No thrombus and immune response leading to unwanted interaction and incorporation of nanoparticles by endothelium and organs, except filtration by the kidneys, was observed. In fact, more than 80% of 99mTc-DTPA-TZMB@Fe3O4 nanoparticles seems to be cleared by the renal pathway but the implanted tumor whose seems to increase the expression of HER2 receptors enhancing the uptake by all other organs. CONCLUSION: However, even in this unfavorable situation the tumor bioconcentrated much larger amounts of the nano-agent than normal tissues giving clear enough contrast for breast cancer imaging for diagnostics purpose by both SPECT and PET technique. Graphical Abstract ᅟ.

SPECT-CT Comparison of Lung Deposition using a System combining a Vibrating-mesh Nebulizer with a Valved Holding Chamber and a Conventional Jet Nebulizer: a Randomized Cross-over Study.

PURPOSE: To compare in vivo the total and regional pulmonary deposition of aerosol particles generated by a new system combining a vibrating-mesh nebulizer with a specific valved holding chamber and constant-output jet nebulizer connected to a corrugated tube. METHODS: Cross-over study comparing aerosol delivery to the lungs using two nebulizers in 6 healthy male subjects: a vibrating-mesh nebulizer combined with a valved holding chamber (Aerogen Ultra®, Aerogen Ltd., Galway, Ireland) and a jet nebulizer connected to a corrugated tube (Opti-Mist Plus Nebulizer®, ConvaTec, Bridgewater, NJ). Nebulizers were filled with diethylenetriaminepentaacetic acid labelled with technetium-99 m (99mTc-DTPA, 2 mCi/4 mL). Pulmonary deposition of 99mTc-DTPA was measured by single-photon emission computed tomography combined with a low dose CT-scan (SPECT-CT). RESULTS: Pulmonary aerosol deposition from SPECT-CT analysis was six times increased with the vibrating-mesh nebulizer as compared to the jet nebulizer (34.1 ± 6.0% versus 5.2 ± 1.1%, p < 0.001). However, aerosol penetration expressed as the three-dimensional normalized ratio of the outer and the inner regions of the lungs was similar between both nebulizers. CONCLUSIONS: This study demonstrated the high superiority of the new system combining a vibrating-mesh nebulizer with a valved holding chamber to deliver nebulized particles into the lungs as comparted to a constant-output jet nebulizer with a corrugated tube.

Micron-sized and submicron-sized aerosol deposition in a new ex vivo preclinical model.

BACKGROUND: The knowledge of where particles deposit in the respiratory tract is crucial for understanding the health effects associated with inhaled drug particles. METHOD: An ex vivo study was conducted to assess regional deposition patterns (thoracic vs. extrathoracic) of radioactive polydisperse aerosols with different size ranges [0.15 µm-0.5 µm], [0.25 µm-1 µm] and [1 µm-9 µm]. SPECT/CT analyses were performed complementary in order to assess more precisely the regional deposition of aerosols within the pulmonary tract. Experiments were set using an original respiratory tract model composed of a human plastinated head connected to an ex vivo porcine pulmonary tract. The model was ventilated by passive expansion, simulating pleural depressions. Aerosol was administered during nasal breathing. RESULTS: Planar scintigraphies allowed to calculate the deposited aerosol fractions for particles in the three size ranges from sub-micron to micron The deposited fractions obtained, for thoracic vs. extra-thoracic regions respectively, were 89 ± 4 % vs. 11 ± 4 % for [0.15 µm-0.5 µm], 78 ± 5 % vs. 22 ± 5 % for [0.25 µm-1 µm] and 35 ± 11 % vs.65 ± 11 % for [1 µm-9 µm]. CONCLUSION: Results obtained with this new ex vivo respiratory tract model are in good agreement with the in vivo data obtained in studies with baboons and humans.

Comparison of Renal Function between Robot-Assisted and Open Partial Nephrectomy as Determined by Tc 99m-DTPA Renal Scintigraphy.

We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time.

Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides.

Laser stimulation of the acupoint 'Zusanli' (ST.36) on the radiopharmaceutical biodistribution in Wistar rats.

Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the 'Zusanli' acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na(99m)TcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm(2)) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na(99m)TcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/ g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

Comparison of Renal Function between Robot-Assisted and Open Partial Nephrectomy as Determined by Tc 99m-DTPA Renal Scintigraphy

We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time.

γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206).

γ-Tilmanocept ((99m)Tc-labeled-tilmanocept or [(99m)Tc]-tilmanocept) is the first mannose-containing, receptor-directed, radiolabeled tracer for the highly sensitive imaging of sentinel lymph nodes in solid tumor staging. To elucidate the mannose-binding receptor that retains tilmanocept in this microenvironment, human macrophages were used that have high expression of the C-type lectin mannose receptor (MR; CD206). Cy3-labeled tilmanocept exhibited high specificity binding to macrophages that was nearly abolished in competitive inhibition experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on macrophages deficient in the MR by small interfering RNA treatment and was increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed colocalization of Cy3-tilmanocept with the macrophage membrane MR and binding of labeled tilmanocept to MR(+) cells (macrophages and/or dendritic cells) in human sentinel lymph node tissues. Together these data provide strong evidence that CD206 is a major binding receptor for γ-tilmanocept. Identification of CD206 as the γ-tilmanocept-binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases.

Chemical stability of (99m)Tc-DTPA under aerobic and microbially mediated Fe(III)-reducing conditions in porous media.

(99m)Tc-DTPA has been used as a conservative tracer to quantify water transport through porous media. However, more information on the reactivity of this (99m)Tc compound under varying geochemical conditions is desirable to better understand its potential uses. We measured the speciation of Tc following amendment of (99m)Tc-DTPA to batch systems spanning a range of controlled biogeochemical conditions. Our results suggest that (99m)Tc-DTPA is stable under the reducing conditions tested. However, freshly precipitated Al-ferrihydrite may displace Tc(IV) from DTPA in the absence of Fe(III)-reducing conditions.

Assessment of hepatic functional regeneration after hepatectomy using (99m)Tc-GSA SPECT/CT fused imaging.

BACKGROUND: The liver itself regenerates after hepatectomy but little is known about how much hepatic function recovers during the regeneration. The liver uptake value (LUV), calculated from Tc-99m-labeled galactosyl-human-serum-albumin ((99m)Tc-GSA) SPECT/CT fused images, is reliable and useful for evaluating hepatic function. In this study, we evaluated the clinical usefulness of LUV for estimating hepatic functional regeneration after hepatectomy. METHODS: We enrolled 95 patients who had undergone (99m)Tc-GSA SPECT/CT tests before/on days 30 and 90 after hepatectomy. We determined the LUV from the (99m)Tc-GSA SPECT/CT images and calculated the %LUV (postoperative LUV/preoperative LUV × 100). Based on surgical procedures and histopathological damage, we divided the study population into patients with severe (n = 12) or non-severe fibrosis (n = 33) who had undergone minor hepatectomy, and patients with severe (n = 14) or non-severe fibrosis (n = 36) having major hepatectomy. On the 90th post-hepatectomy day, five patients manifested liver failure; in these patients, we analyzed the co-relation between liver failure and the results of the liver function tests performed on day 30 after surgery. RESULTS: Although the %LUV reached 95.4 ± 12.2 % in 30 days, in patients with severe fibrosis after major hepatectomy it remained below 90 %. Patients having low %LUV (<75 %) and high serum bilirubin (>2.0 mg/dl) at 30 days showed a relative risk of liver failure of 12.0 and 4.5 (p < 0.001 and p < 0.001), respectively. CONCLUSIONS: Although the %LUV recovered to about 95 % in all patients within 30 days after the hepatectomy, in patients with severe fibrosis having major hepatectomy, the process of recovery was delayed. The %LUV corresponded to the quality of the liver function which emerged in a later post-hepatectomy phase.

Fluorescent-tilmanocept for tumor margin analysis in the mouse model.

BACKGROUND: Dendritic cells (DC) are localized in close proximity to cancer cells in many well-known tumors, and thus maybe a useful target for tumor margin assessment. MATERIALS AND METHODS: [(99m)Tc]- cyanine 7 (Cy7)-tilmanocept was synthesized and in vitro binding assays to bone marrow-derived DC were performed. Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma tumors, were administered 1.0 nmol of [(99m)Tc]-Cy7-tilmanocept via tail vein injection. After fluorescence imaging 1 or 2 h after injection, the tumor, muscle, and blood were assayed for radioactivity to calculate percent-injected dose. Digital images of the tumors after immunohistochemical staining for DC were analyzed to determine DC density. RESULTS: In vitro binding demonstrated subnanomolar affinity of [(99m)Tc]-Cy7-tilmanocept to DC (KA = 0.31 ± 0.11 nM). After administration of [(99m)Tc]-Cy7-tilmanocept, fluorescence imaging showed a 5.5-fold increase in tumor signal as compared with preinjection images and a 3.3-fold difference in fluorescence activity when comparing the tumor with the surgical bed after tumor excision. Immunohistochemical staining analysis demonstrated that DC density positively correlated with tumor percent of injected dose per gram (r = 0.672, P = 0.03), and higher DC density was observed at the periphery versus center of the tumor (186 ± 54 K versus 64 ± 16 K arbitrary units, P = 0.001). CONCLUSIONS: [(99m)Tc]-Cy7-tilmanocept exhibits in vitro and in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.

Synthesis and evaluation of Tc-99m DTPA-glutathione as a non-invasive tumor imaging agent in a mouse colon cancer model.

PURPOSE: Glutathione (GSH) plays a critical role in detoxification reactions by reducing the levels of reactive oxygen species in cancer cells. This study aimed to develop technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA)-GSH as a tumor imaging agent, and to evaluate the diagnostic performance of Tc-99m DTPA-GSH in terms of its ability to differentiate tumors from inflammatory lesions. METHODS: DTPA-GSH was synthesized by reaction of GSH with DTPA anhydride under anhydrous conditions in a nitrogen atmosphere. DTPA-GSH was then reacted with Tc-99m sodium pertechnetate in a tin (II) chloride (SnCl2) solution. Gamma camera imaging was performed after intravenous injection of Tc-99m DTPA-GSH into a mouse CT-26 colon cancer model, or a mouse model of inflammation induced by the intramuscular injection of Freund's complete adjuvant. RESULTS: DTPA-GSH was successfully prepared via a straightforward synthetic procedure and radiolabeled with Tc-99m at a high labeling efficiency (>95%). Tc-99m DTPA-GSH was strongly internalized by tumors in colon cancer model mice, with the tumor-to-normal muscle ratio of the complex reaching 4.3±0.9 at 4 h. By contrast, Tc-99m DTPA-GSH showed relatively weak uptake in inflammatory lesions (target-to-non-target ratio=2.0±0.3 at 4 h). A competition study showed that the uptake of Tc-99m DTPA-GSH into tumors was blocked by co-injection with high concentrations of free GSH. CONCLUSIONS: The results of this work indicate that Tc-99m DTPA-GSH is a good candidate for development as a non-invasive tumor imaging agent. Furthermore, Tc-99m DTPA-GSH effectively distinguished between cancerous tissue and inflammatory lesions.