Quantitative salivary gland SPECT/CT using deep convolutional neural networks.

Quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate aids in evaluating salivary gland function. However, gland segmentation and quantitation of gland uptake is challenging. We develop a salivary gland SPECT/CT with automated segmentation using a deep convolutional neural network (CNN). The protocol comprises SPECT/CT at 20 min, sialagogue stimulation, and SPECT at 40 min post-injection of Tc-99m pertechnetate (555 MBq). The 40-min SPECT was reconstructed using the 20-min CT after misregistration correction. Manual salivary gland segmentation for %injected dose (%ID) by human experts proved highly reproducible, but took 15 min per scan. An automatic salivary segmentation method was developed using a modified 3D U-Net for end-to-end learning from the human experts (n = 333). The automatic segmentation performed comparably with human experts in voxel-wise comparison (mean Dice similarity coefficient of 0.81 for parotid and 0.79 for submandibular, respectively) and gland %ID correlation (R2 = 0.93 parotid, R2 = 0.95 submandibular) with an operating time less than 1 min. The algorithm generated results that were comparable to the reference data. In conclusion, with the aid of a CNN, we developed a quantitative salivary gland SPECT/CT protocol feasible for clinical applications. The method saves analysis time and manual effort while reducing patients' radiation exposure.

Comparison of a manometric tear duct irrigation test with dacryoscintigraphy in the investigation of epiphora.

PURPOSE: Assessment of lacrimal resistance in patients with patent lacrimal systems is important in determining whether dacryocystorhinostomy (DCR) surgery is appropriate. Current techniques, including lacrimal syringing and dacryoscintigraphy (DSG), can be unreliable. We compare the results of a manometric tear duct test (mTDT) irrigation technique with DSG in these patients. METHODS: All symptomatic patients in a specialist lacrimal clinic had full work-up apart from syringing. Lacrimal resistance was assessed using mTDT which applies a fixed head of fluid pressure via a cannula sealed to punctum. Conventional syringing was also performed in cases with abnormal mTDT. Symptomatic patients with delayed tear clearance, no external cause for watering and patent lacrimal systems had DSG. MTDT and DSG results were compared, including in asymptomatic fellow eyes. RESULTS: 105 tear ducts were examined, 85 symptomatic. Symptomatic eyes had a significantly higher mean mTDT resistance (p = .0003) and more had abnormal mTDT (52%) compared to asymptomatic eyes (10%). Although mean tear duct resistance was higher in those with nasolacrimal duct stenosis (NLDS) than freely patent (FP) on syringing (8.5 vs 10.8 dpm), this was not significant (p = .6). High proportions of both FP and NLDS groups had no flow at all on mTDT (60% and 53%, respectively). DSG showed no significant difference in the symptomatic versus asymptomatic eyes (p = .36), nor between those with a normal or abnormal mTDT (p = .25), nor between FP and NLDS groups (p = .25). CONCLUSIONS: In contrast to DSG, the mTDT provides valuable, objective information on lacrimal resistance that can guide a decision to DCR surgery.

Enhanced noninvasive imaging of oncology models using the NIS reporter gene and bioluminescence imaging.

Noninvasive bioluminescence imaging (BLI) of luciferase-expressing tumor cells has advanced pre-clinical evaluation of cancer therapies. Yet despite its successes, BLI is limited by poor spatial resolution and signal penetration, making it unusable for deep tissue or large animal imaging and preventing precise anatomical localization or signal quantification. To refine pre-clinical BLI methods and circumvent these limitations, we compared and ultimately combined BLI with tomographic, quantitative imaging of the sodium iodide symporter (NIS). To this end, we generated tumor cell lines expressing luciferase, NIS, or both reporters, and established tumor models in mice. BLI provided sensitive early detection of tumors and relatively easy monitoring of disease progression. However, spatial resolution was poor, and as the tumors grew, deep thoracic tumor signals were massked by overwhelming surface signals from superficial tumors. In contrast, NIS-expressing tumors were readily distinguished and precisely localized at all tissue depths by positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging. Furthermore, radiotracer uptake for each tumor could be quantitated noninvasively. Ultimately, combining BLI and NIS imaging represented a significant enhancement over traditional BLI, providing more information about tumor size and location. This combined imaging approach should facilitate comprehensive evaluation of tumor responses to given therapies.

Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study.

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

99mTc-Pertechnetate Scintigraphy Predicts Successful Postoperative Ablation in Differentiated Thyroid Carcinoma Patients Treated with Low Radioiodine Activities.

BACKGROUND: Postoperative routine radioiodine (RAI) treatment is currently debated for patients with low-risk differentiated thyroid carcinoma (DTC) patients. If performed, a low ¹³¹I activity (i.e., 1 to 2 GBq) is recommended with the aim to ablate thyroid remnant and facilitate subsequent follow-up by thyroglobulin measurement. The purpose of this study was to evaluate the relationship between postsurgical technetium-99m (99mTc)-pertechnetate scintigraphy and the rate of successful remnant ablation after low activity radioiodine ablation in patients with DTC. METHODS: Enrolled were 193 patients with low risk DTC who underwent total thyroidectomy and RAI ablation with a fixed 1.1 GBq activity of ¹³¹I. 99mTc-pertechnetate scans were done and thyrotropin stimulated thyroglobulin (sTg) levels measured just before ablation. Ablation effectiveness was assessed 6 to 12 months later by sTg measurement, neck ultrasound and diagnostic whole body scan. RESULTS: A negative 99mTc-perthecnetate scans was the best predictor of successful ablation (P<0.001) followed by preablative sTg levels <0.8 ng/mL (P=0.008) and 99mTc-pertechnetate uptake rate values <0.9% (P=0.065). Neither sex nor age of the patient at the time of ablation or tumor histology and size showed a significant association with the rate of successful ablation. CONCLUSION: The 99mTc-pertechnetate scintigraphy is a simple and feasible tool to predict effectiveness of low activity ¹³¹I thyroid to ablate thyroid remnants in patients with DTC.

Green synthesis of labeled CeO2 nanoparticles with 99mTc and its biodistribution evaluation in mice.

AIMS: The in vivo targeted diagnostic applications of biosynthetic Cerium oxide nanoparticles (CeO2-NPs), prepared by applying chitosan as a stabilizer, was explored by evaluating the cytotoxicity through MTT assay on WEHI 164 cell line, the Hemolytic activity of CeO2-NPs and biodistribution in rats. MAIN METHODS: The CeO2-NPs were characterized through the use of TGA/DTG, PXRD, FESEM, FTIR, and UV-Vis spectroscopy. The biodistribution of CeO2-NPs were determined by directly labeled nanoparticles with Technetium-99 m (99mTc) radioisotope (99mTc-CeO2-NPs). The labeling efficiency and stability of 99mTc-CeO2-NPs were also measured with Instant Thin Layer Chromatography (ITLC) method. The saturation study was investigated by 1 mCi of 99mTc-CeO2-NPs using different concentrations of WEHI 164 cells after 4 h of incubation. In vivo biodistribution study was performed by intravenous injection of 600 µCi/200 µL 99mTc-CeO2-NPs through rat's tail. KEY FINDINGS: CeO2-NPs seemed to have a low cytotoxic effect on WEHI 164 cell line and did not result in hemolysis. The biodistribution of CeO2-NPs has shown that a huge amount of 99mTc-CeO2-NPs was amassed in the living human organs, including liver, lung, spleen, stomach, and thyroid which shows the in vivo stability of the labeled conjugate. Herein, we have developed a facile, economical, and greener synthetic procedure applying Chitosan template. This green approach is comparable to conventional methods that utilize hazardous materials which are would be a suitable alternative to circumvent synthetic issues related to these materials. SIGNIFICANCE: The bio-applications of nano-sized CeO2-NPs were explored to find new horizon to use nanotechnology as the diagnostic tool.

Predictive value of scintigraphic (semi-)quantitative thyroid parameters on radioiodine therapy outcome in hyperthyroid cats.

Objectives The outcome of radioiodine therapy in hyperthyroid cats is suspected to be influenced by multiple factors. The degree of activity of the thyroid gland, represented by uptake of sodium pertechnetate or tracer activities of radioiodine by the thyroid gland on thyroid scintigraphy, has been suggested in the literature as one of those. Thyroid gland pertechnetate uptake can be represented by (semi-)quantitative factors such as the thyroid to salivary gland (T/S) ratio, the thyroid to background (T/B) ratio and the percentage technetium uptake by the thyroid glands (%TcU). The aim of this study was to investigate a possible relationship between these thyroid scan parameters and radioiodine therapy outcome. Methods Sodium pertechnetate thyroid scans of 75 hyperthyroid cats were retrospectively evaluated and statistical analysis was performed with and without correction for injected radioiodine activity. Three different background regions of interest (ROIs) were used to calculate the T/B ratio and %TcU: 'neck', 'circle' and 'copy ROI'. Results Higher T/S ratios were found to be significantly related to a persistent hyperthyroid outcome in both analyses. For the T/S ratio, a threshold value of 5.4 was determined, with a sensitivity of 73% and a specificity of 59%. An increased risk for persistent hyperthyroidism compared with a final euthyroid outcome with an increased T/Bcircle ratio was only found to be significant without correction for the activity of radioiodine administered. For the %TcU no statistical significance was reached. Regarding a low total thyroxine outcome, no significant relationships with any of the investigated parameters were found. Conclusions and relevance The findings of this study suggest that semi-quantification of thyroid gland uptake is best performed using the T/S ratio. A T/S ratio ⩾5.4 is a possible indicator for an increased risk of persistent hyperthyroidism.

99mTc-pertechnetate-avid metastases from differentiated thyroid cancer are prone to benefit from 131I therapy: A prospective observational study.

The aim of this study is to determine the contribution of neck and chest Tc-pertechnetate scan to the management of postoperative patients with suspicious metastatic differentiated thyroid cancer (DTC), particularly to the prediction of response to radioiodine (I) therapy. Just before I administration, a total of 184 postoperative DTC patients with stimulated serum thyroglobulin (ssTg) >10 ng/mL were enrolled to undergo neck and chest Tc-pertechnetate scan, which were directly compared with post-therapeutic I scan to determine the concordance of site and number of metastatic lesions. The percentage changes in ssTg between Tc-pertechnetate-avid group and Tc-pertechnetate-nonavid group were compared, and the response to I in both groups was analyzed according to the nature of Tc-pertechnetate avidity as well. The percentages of concordance between Tc-pertechnetate and I scan in detecting metastases were 65.7% and 26.0% in per-patient and per-site analyses with low unweighted kappa, respectively. Tc-pertechnetate scan led to a change in therapeutic decision making in 19/184 (10.3%) patients. In 72 patients with I-avid metastases, the ssTg in Tc-pertechnetate-avid group (n = 13) decreased significantly compared with that in Tc-pertechnetate-nonavid group (n = 59) (median: -81.56% vs -48.14%; Z = -4.276, P = .000). The difference of therapeutic response between Tc-pertechnetate-avid group and Tc-pertechnetate-nonavid group was statistically significant (χ = 8.4; P = .03). Although the consistency between Tc-pertechnetate scan before I administration and post-therapy I scan in detecting metastases is low, identifying metastases in postoperative DTC patients with elevated ssTg via Tc-pertechnetate scan prior to I therapy provides incremental value for therapeutic decision making. Notably, patients with Tc-pertechnetate-avid metastases may be more prone to benefit from I therapy than those with Tc-pertechnetate-nonavid metastases.

Identifying the heterogeneity of COPD by V/P SPECT: a new tool for improving the diagnosis of parenchymal defects and grading the severity of small airways disease.

INTRODUCTION: Airway obstruction and possible concomitant pulmonary diseases in COPD cannot be identified conventionally with any single diagnostic tool. We aimed to diagnose and grade COPD severity and identify pulmonary comorbidities associated with COPD with ventilation/perfusion single-photon emission computed tomography (V/P SPECT) using Technegas as the functional ventilation imaging agent. METHODS: 94 COPD patients (aged 43-86 years, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-IV) were examined with V/P SPECT and spirometry. Ventilation and perfusion defects were analyzed blindly according to the European guidelines. Penetration grade of Technegas in V SPECT measured the degree of obstructive small airways disease. Total preserved lung function and penetration grade of Technegas in V SPECT were assessed by V/P SPECT and compared to GOLD stages and spirometry. RESULTS: Signs of small airway obstruction in the ventilation SPECT images were found in 92 patients. Emphysema was identified in 81 patients. Two patients had no signs of COPD, but both of them had a pulmonary embolism, and in one of them we also suspected a lung tumor. The penetration grade of Technegas in V SPECT and total preserved lung function correlated significantly to GOLD stages (r=0.63 and -0.60, respectively, P<0.0001). V/P SPECT identified pulmonary embolism in 30 patients (32%). A pattern typical for heart failure was present in 26 patients (28%). Parenchymal changes typical for pneumonia or lung tumor were present in several cases. CONCLUSION: V/P SPECT, using Technegas as the functional ventilation imaging agent, is a new tool to diagnose COPD and to grade its severity. Additionally, it revealed heterogeneity of COPD caused by pulmonary comorbidities. The characteristics of these comorbidities suggest their significant impact in clarifying symptoms, and also their influence on the prognosis.

Preoperative Diagnostic Strategy for Parotid Gland Tumors Using Diffusion-Weighted MRI and Technetium-99m Pertechnetate Scintigraphy: A Prospective Study.

OBJECTIVE: Fine needle aspiration cytology (FNAC) for diagnosis of a parotid gland tumor is widely used but its sensitivity is low and non-diagnostic rate is relatively high. In contrast, core needle biopsy (CNB) has a higher sensitivity and lower rate of sampling errors but has a higher risk of injury to adjacent organs such as facial nerve than FNAC. Screening of patients with parotid gland tumors to identify cases of pleomorphic adenoma (PA) and Warthin tumor (WT) may allow CNB to be confined to patients without PA and WT. We established an algorithm for preoperative diagnosis and management of parotid gland tumor using diffusion-weighted MRI and 99mTc pertechnetate scintigraphy. This algorithm was developed with the goal of maximal reduction of the number of patients in whom CNB is required. The purpose of the study is to validate our algorithm prospectively. METHODS: A prospective study was conducted in 71 cases who were newly diagnosed with parotid gland tumor and 53 cases were enrolled in the study. In the algorithm, PA (high apparent diffusion coefficient (ADC) mean≥1.5×10(-3) mm(2)/s) and non-PA (low ADCmean<1.5×10(-3) mm(2)/s) cases are first distinguished based on the ADCmean on diffusion-weighed MRI. Second, among suspected non-PA cases, WT and non-WT are distinguished using technetium-99m pertechnetate scintigraphy. CNB is then performed only in probable non-PA and non-WT cases. RESULTS: Although CNB was only required in 40% (21/53) of all cases, we made a preoperative histopathological diagnosis with an accuracy of 87% (46/53) and we correctly diagnosed whether a tumor was benign or malignant with an accuracy of 96% (51/53). Preoperative surgical planning had to be changed during surgery in only one case (2%). CONCLUSIONS: Our algorithm is valuable in terms of clinical practice with highly potential for preoperative diagnosis and with less risk of CNB procedure.

Determination of in vivo behavior of mitomycin C-loaded o/w soybean oil microemulsion and mitomycin C solution via gamma camera imaging.

In this study, a microemulsion system was evaluated for delivery of mitomycin C (MMC). To track the distribution of the formulated drug after intravenous administration, radiochemical labeling and gamma scintigraphy imaging were used. The aim was to evaluate a microemulsion system for intravenous delivery of MMC and to compare its in vivo behavior with that of the MMC solution. For microemulsion formulation, soybean oil was used as the oil phase. Lecithin and Tween 80 were surfactants and ethanol was the cosurfactant. To understand the whole body localization of MMC-loaded microemulsion, MMC was labeled with radioactive technetium and gamma scintigraphy was applied for visualization of drug distribution. Radioactivity in the bladder 30 minutes after injection of the MMC solution was observed, according to static gamma camera images. This shows that urinary excretion of the latter starts very soon. On the other hand, no radioactivity appeared in the urinary bladder during the 90 minutes following the administration of MMC-loaded microemulsion. The unabated radioactivity in the liver during the experiment shows that the localization of microemulsion formulation in the liver is stable. In the light of the foregoing, it is suggested that this microemulsion formulation may be an appropriate carrier system for anticancer agents by intravenous delivery in hepatic cancer chemotherapy.

[Evaluation of the performance of transfer devices in a closed system using a radioactive solution of [(99m)Tc]]. / Évaluation de la performance de dispositifs de transfert en système clos au moyen d'une solution radioactive de [(99m)Tc].

INTRODUCTION: The exposure of workers to antineoplastic agents is potentially dangerous in the long term because of the teratogenic, carcinogenic and mutagenic hazardous of these products. These risks could be reduced by individual and collective shield measures. It's recommended to use transfer devices in a closed system for preparation of chemotherapy. METHOD: The aim of the survey is to analyse for five devices (four devices in a closed system transfer and a needle equipped with an air intake), the following criteria: transfer performance of a solution of a vial to another one, no leakage of the device and practicality in the use. A method implementing a radioactive solution of sodium pertechnetate [(99m)Tc] is used. RESULTS: Teva(®) and Cardinal(®) devices seem to be more efficient according to the ability to transfer one solution from a vial to another one with a low dead volume and low-level contamination in the around of the manipulation area. The Hospira(®) device appears an intermediate solution, while the Phaseal(®) device may be irrelevant for the transfer of a solution. DISCUSSION-CONCLUSION: Our study could attest that the methodology is simple to implement and cheap to compare devices on multiple selection criteria. This evaluation method is interesting because it allows a classification according to several criteria weighted according to the type of intended use. In addition to economic issues and protection of the worker, the use of such devices should be extended to other areas as the preparation of chemotherapy such as preparation of radiopharmaceuticals drugs.

Design considerations for incorporating sodium iodide symporter reporter gene imaging into prostate cancer gene therapy trials.

This study was done to aid in the design of a phase I gene therapy trial in patients with prostate cancer. We determined the dosimetric characteristics of our reporter gene system when coupled with intravenous administration of radioactive sodium pertechnetate (Na(99m) TcO(4)) and determined the feasibility of using human sodium iodide symporter (hNIS) as a reporter gene to study the dynamics of adenoviral transgene expression in a large animal tumor. A replication-competent Ad5-yCD/mutTK(SR39) rep-hNIS adenovirus was injected into the prostate gland of dogs for dosimetry purposes, and into a canine soft tissue sarcoma (STS) for imaging purposes. After resection of the prostate, the amount of (99m)TcO(4)() sequestered in the prostate was determined, the radiation dose absorbed by the prostate and nontarget critical organs was calculated, and hNIS reporter gene expression was imaged in the STS by single-photon emission computed tomography (SPECT). On the basis of the findings from 25 dogs, the amount of (99m)TcO (4)() sequestered in the prostate ranged from 13 to 276 muCi. Using the highest value observed, absorbed radiation dose to critical organs was calculated and found to be below U.S. Food and Drug Administration limits for diagnostic imaging. Also, (99m)TcO (4)() uptake was readily detected by SPECT and found to persist in vivo for at least 4 days. On the basis of our dosimetry calculations, up to five imaging procedures can be safely performed in humans after intraprostatic injection of the Ad5-yCD/mutTK(SR39)rep-hNIS adenovirus and the hNIS reporter gene system can be used to study the dynamics of adenoviral gene therapy vectors in large animal tumors.

Lower eyelid laxity in functional acquired epiphora: evaluation with quantitative scintigraphy.

PURPOSE: The examination of lacrimal drainage is often based on qualitative criteria. This study uses quantitative scintigraphy to evaluate "functional" epiphora. METHODS: Thirty-two patients with functional epiphora (no morphologic abnormalities of the conjunctiva and eyelids, a patent nasolacrimal duct on irrigation, and no anatomical stenosis on dacryocystography) were studied (study group, SG). Twenty-two individuals without epiphora were also examined (control group, CG). Fifty microliters of Technetium-99m was instilled into the conjunctival cul-de-sac. Time-activity curves were then constructed, and conjunctival lacrimal clearance (CLC) at 2.5, 5, 7.5, and 10 minutes was calculated. Differences in CLC between the SG and the CG and correlations between CLC and horizontal and median tendon laxity and eyelid length in the SG were examined. RESULTS: The SG had significantly reduced CLC at 2.5 and 5 minutes, compared with the CG (p = 0.01 and p = 0.04, respectively), whereas respective differences at 7.5 and 10 minutes were not statistically significant. In the SG, CLC at 2.5 and 5 minutes was significantly correlated with horizontal and median tendon laxity. The respective correlation with eyelid length was not statistically significant. Furthermore, in the SG, CLC at 2.5 and 5 minutes was significantly correlated with patient age (p = 0.03 and p = 0.04, respectively). Differences in CLC between men and women were not statistically significant at all intervals. CONCLUSIONS: The correlation between eyelid laxity and CLC supports the role of the eyelid "pump" in lacrimal drainage. CLC at 2.5 and 5 minutes may be used to decide treatment methods for functional epiphora.

Clinical utility of co-registered respiratory-gated( 99m)Tc-Technegas/MAA SPECT-CT images in the assessment of regional lung functional impairment in patients with lung cancer.

PURPOSE: The aim of the study was to provide preliminary validation of the utility of co-registered respiratory-gated ventilation/perfusion single-photon emission computed tomography-computed tomography (SPECT-CT) images in the assessment of regional lung functional impairment in patients with lung cancer. METHODS: Twenty untreated and three radiotherapy-treated patients with lung cancer underwent gated( 99m)Tc-Technegas/macroaggregated albumin (MAA) SPECT, using a triple-headed SPECT unit and a respiratory synchroniser. Gated SPECT images were obtained from 1/8 data centered at peak inspiration for each regular respiratory cycle and co-registered with tidal inspiration CT images using an automated three-dimensional registration tool. RESULTS: Gated SPECT images detected 10.2% more ventilation defects (205 vs 186) and 9% more perfusion defects (218 vs 200) compared with ungated images, with a significantly higher lesion-to-normal lung contrast ( P<0.0001). Co-registered gated SPECT-CT images accurately visualised the anatomy of ventilation and/or perfusion defects associated with bronchial and/or vascular involvement by tumours, resulting in changes in surgical planning in two patients with lung cancer. In the three patients who had received radiotherapy, perfusion defects along the radiation field were identified even in the lung areas without abnormal opacities on CT images. In the operated patients, the co-registered gated SPECT-CT images allowed accurate placement of regions of interest over the lung lobes to be resected, yielding a significantly better prediction of postoperative forced expired volume in 1 s (FEV(1)) compared with that predicted without use of these images ( R=0.993 vs R=0.890; P<0.05), with an excellent inter-observer reproducibility. CONCLUSION: Detailed functional-morphological correlation on co-registered gated SPECT-CT images contributes to accurate assessment of regional functional impairment, and may be useful for surgical planning, prediction of postoperative function and assessment of external beam radiotherapy effects in patients with lung cancer.

Usefulness of per-rectal portal scintigraphy with technetium-99m pertechnetate for prognosis of primary biliary cirrhosis.

BACKGROUND/AIMS: Conventional methods predicting survival in patients with primary biliary cirrhosis are based on the results of blood tests and on clinical condition, both of which may be affected by treatment. Portal circulation can be evaluated in a relatively noninvasive manner by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics and assess prognosis in patients with primary biliary cirrhosis. METHODOLOGY: Per-rectal portal scintigraphy with Tc-99m pertechnetate was done in 51 patients with primary biliary cirrhosis. A solution containing Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. The per-rectal portal shunt index was calculated from the curves. RESULTS: The shunt index was higher in patients with stage IV primary biliary cirrhosis than in those with stage I, II, or III primary biliary cirrhosis. On the basis of portal shunt index, the patients were divided into those with a shunt index of less than 18%, and those with a shunt index of 18% or more. The cumulative survival rate was lower among patients with the higher shunt index. On regression analysis, the portal shunt index was found to be significantly related to survival. CONCLUSIONS: Our results indicate that per-rectal portal scintigraphy with Tc-99m pertechnetate can be used to non-invasively evaluate the portal circulation of patients with primary biliary cirrhosis and is useful in establishing prognosis in such patients.

Biodistribution of dual radiolabeled lipidic nanocapsules in the rat using scintigraphy and gamma counting.

The aim of the present work was to study the biodistribution of a radiolabeled lipidic nanocapsule formulation after intravenous administration in rat by scintigraphy and gamma counting. This formulation is expected to be used as anticancer agent delivery devices and as transfection complexes. For this purpose, 99mTc-oxine was incorporated in the lipidic core, while 125I labeled tensioactive shell of the nanocapsule. First, in vitro stability of radiolabeled nanocapsules was evaluated by dialysis against distilled water and size measurements. Second, the nanocapsule biodistribution was followed after intravenous administration for 3 h by dynamic scintigraphic acquisition and up to 24 h by determining the gamma activity in blood and tissues. Radiolabeling was efficient and stable in vitro. After intravenous injection blood radioactivity decreased with an early half disappearance time of about 45 min for both radioisotopes. Liver and intestine radioactivities raised up to 24 h. The relatively long remanence in blood of the tracers which is probably due to the presence of PEG at the nanocarrier surface seems promising for the use of these solvent free lipidic nanocapsules as carrier of lipophilic drugs.

Migration pathways of hypodermically injected technetium-99m in dogs.

Hypodermic injection of technetium-99m (99mTc-pertechnetate) at points of low electrical resistance give rise to rapid, longitudinal, and progressive diffusion of the radioactive tracer. We assessed the effect of cutaneous incisions that did not intersect the migration trajectory of 99mTc-pertechnetate and the re-establishment of pathways after the suture of incisions that intersected the migration trajectory. Linear and rapid migration of 99mTc-pertechnetate was not altered or prevented by incisions that did not intersect the migration pathway. Different patterns of 99mTc-pertechnetate spread were found when incisions intersected the radioactive pathways until restoration of the normal migration pathway observed in undamaged skin occurred. In all experiments in which migration of 99mTc-pertechnetate was observed, lavage of surgical wounds was followed by disappearance of the 99mTc-pertechnetate migration observed around the suture. Linear migration of the tracer was not observed when the incision was left uncovered, filled with petroleum jelly, or with a solid silicone sheet, but it was seen when non-sutured incisions were filled with transonic or silicone gel or covered with a solid silicone sheet parallel to the cutaneous plane. These data show that after a cutaneous incision that intersected the diffusion trajectory of the radioactive tracer, linear migration of 99mTc-pertechnetate hypodermically injected at points of low electrical resistance was restored before healing of the cutaneous incision and was independent of incisions made on the skin not overlying the radioactive pathway. A mechanism similar to that of capillary electrophoresis is suggested to explain the hypodermic diffusion of inert particles through specific and constant linear pathways.

Technetium-99m-antiepidermal growth factor-receptor antibody in patients with tumors of epithelial origin: part II. Pharmacokinetics and clearances.

UNLABELLED: Radiolabeled antitumor antibodies hold promise for diagnostic imaging and therapy in oncology. The purpose of this study was to investigate the pharmacokinetics, clearances and possible differences of two dosage administrations of the 99mTc-labeled antiepidermal growth factor (EGF)-receptor antibody and to predict the best dose and schedule for future clinical evaluations of this radiopharmaceutical. METHODS: Nine patients (4 women, 5 men; mean age 46.4 +/- 14.0 yr) were administered 1-3 mg 99mTc-labeled anti-EGF-receptor antibody (a murine IgG2a isotype) by intravenous bolus infusion. After administration, blood samples were collected from 7 patients from an antecubital vein opposite to the injection side at intervals from 2 min to 24 hr after injection, and plasma samples were obtained for pharmacokinetic analysis. Appropriate plasma samples were examined for isotope clearance (i.e., microCi/ml at various intervals) and 99mTc complexation to plasma proteins by fast protein liquid chromatography (FPLC) analysis. Urine was collected from each patient at 3 hr intervals up to 24 hr after monoclonal antibody administration to monitor 99mTc clearance. Plasma time-activity curves were fitted to a two-compartment model using nonlinear least-squares regression analysis by the method of flexible polyhedrals. RESULTS: Plasma disappearance curves of 99mTc-labeled anti-EGF-receptor antibody were best fit by biexponential equation with a distribution half-life (t(1/2alpha)) of 0.137 +/- 0.076 hr (n = 7) and elimination half-life (t(1/2beta)) of 20.3 +/- 8.0 hr. Analysis of urine showed that activity clearance by this route amounted to 4.9% +/- 0.6% of the injected dose in 24 hr, and FPLC analysis showed no evidence of decomposition, only 6%-7% of 99mTc was in a low molecular weight species. CONCLUSION: Plasma pharmacokinetics and urine clearance indicate comparability in both doses. The pharmacokinetic properties of the 99mTc-labeled anti-EGF-receptor antibody were found to be dose-independent. These findings provide an initial characterization of the radiopharmaceutical disposition in patients and may be used as the basis for calculating a better estimate of biodistribution and dosimetry for patients who will receive 188Re-labeled anti-EGF-receptor antibody (MAb ior egf/r3) injection for radioimmunotherapy and warrants further controlled clinical trials to define the efficacy of the radiopharmaceutical.