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Digital scintigraphy: principles, design, and performance.

In a digital camera the position of a scintillation event is computed following analog-to-digital conversion of photomultiplier pulse charges. Digital position analysis is essentially a mathematical inversion procedure based upon calibrated responses of the photomultipliers to scintillations from a narrow-beamed source that maps a detector's field of view. Operationally, a camera's image characteristics are optimized by means of computer-generated inversion reference tables, individually tailored to the specific response characteristics of each detector. Design considerations indicate that cameras of varied configurations, e.g., linear, disc-shaped, rectangular, or cylindrical, can be analyzed by this method. Also, for any given electro-optical system, energy resolution, spatial characteristics, and event-rate performance can be made superior to analog systems. The measured performances of a one-dimensional test camera, although limited in its optical and electronic design, support this conclusion.

Analog-Digital Conversion↗

[Assessment of transient dilation of the left ventricular cavity in patients with hypertrophic cardiomyopathy by exercise thallium-201 scintigraphy].

Exercise Tl scintigraphy (EX-Tl) provides a noninvasive means of identifying myocardial perfusion abnormalities in patients (pts) with hypertrophic cardiomyopathy (HCM). We have noted that some pts with HCM have a pattern of transient dilation of the left ventricle (LV) on the immediate post exercise images as compared with 3 hour redistribution images. We presumed that left ventricular dilation was caused by subendocardial hypoperfusion. So we studied transient dilation of the LV in 50 pts with HCM and 20 controls (C). Initial and delayed conventional short tomographic images were obtained after reconstruction of 30 projections acquired over 180 degrees. Thirty six radii every 10 degrees were generated from the center of the middle myocardial images of the short axis. An area surrounded by the thirty six points of maximal count on each radius was calculated in initial and delayed images. Transient Dilation Index (TDI) as an index of dilation was determined by dividing an area in initial image by an area in delayed image. TDI in pts with HCM was larger than that in C. Pts with HCM were classified into the two groups, Group A: TDI greater than 1.11 (mean + 2 SD in C), 24 pts, Group B: TDI greater than 1.11, 26 pts. Frequency of pts with history of chest pain in Group A was higher than that in Group B, and frequency of pts with positive exercise ECG in Group A was higher than that in Group B. End diastolic volume in Group B did not change 10 minutes after exercise by radionuclide ventriculography. In conclusion, transient dilation of the LV in pts with HCM by EX-Tl is in appearance, and may reflect subendocardial ischemia.

Adult↗

Indirect mechanisms contribute to biological effects produced by decay of DNA-incorporated iodine-125 in mammalian cells in vitro: double-strand breaks.

We have examined whether nuclear DNA can be protected from double-strand breaks (DSBs) induced by decay of the Auger-electron-emitting radionuclide 125I. Decays were accumulated at 0.3 degrees C in Chinese hamster V79 cells suspended in isotonic buffer containing 0.1 M EDTA in the presence or absence of 10% dimethyl sulfoxide (DMSO). DSBs were measured by the neutral elution method (pH 9.6) and quantified as strand scission factors. DMSO was shown to protect DNA from DSBs caused by the decay of DNA-incorporated 125I. The dose modification factor (DMF) for this radionuclide decreases as a function of 125I decays (389 to 4,100 decays, DMF = 2.5 to 1.3). Extrapolation of the curve for the DMF indicates that at approximately 15,000 decays/cell, a DMF of 1 would be obtained. Experiments using large numbers of 125I decays confirmed these extrapolations. For induction of DSBs by 137Cs gamma rays, the DMF also decreases with dose (50 to 290 Gy, DMF = 2.7 to 1.5). However, extrapolation of the curve for the DMF indicates that protection does not cease at higher doses. The data show that, at the same level of damage, DMSO can protect against gamma-ray-induced DSBs 1.35-fold more efficiently than against DSBs caused by the decay of DNA-incorporated 125I. It appears that when 125I is incorporated into DNA, chromatin structure fosters some DSB formation by an indirect mechanism(s) and that more than one DSB is generated per decaying atom.

Animals↗

Regional specific mean expiratory gas flow from 81mKr equilibrium inhalation data.

A new method of analysing the data available from routine 81m Kr equilibrium inhalation investigations has been developed. The data for analysis are acquired from a gamma camera in the form of a sequential series of images from which multiple breath activity-time curves are generated for eight regions in the lung. The method is based on a description of the behaviour of the radioactive gas in the lung using a mathematical model. Values of specific mean expiratory gas flow, that is mean expiratory gas flow per unit lung volume, are calculated from the application of the model to the expiratory phase only of a single breath activity-time curve which is generated from the multiple breath activity-time curve using post-acquisition gating. This method overcomes the problem of non-uniform inspiratory concentration of tracer gas experienced in previously reported techniques of analysing inhalation data obtained using poorly soluble radioactive gases. The model is shown, in simulation studies, to be an adequate description of the behaviour of radioactive gas in the lung and the analysis technique is shown, in clinical studies, to be both reproducible and sensitive to disease state.

Humans↗

In vivo photoacoustic imaging of blood vessels with a pulsed laser diode.

Photoacoustic imaging is a hybrid imaging modality that is based on the detection of acoustic waves generated by absorption of pulsed light by tissue chromophores such as hemoglobin in blood. For this technique, usually large and costly Q-switched Nd:YAG lasers are used. These lasers provide a pulse energy of at least several milliJoules. In search of alternative light sources, we investigated the use of a small and compact pulsed laser diode to image blood vessels. We proved that a pulsed laser diode can be applied for imaging blood vessels in vivo.

Acoustics↗

A dynamic renal phantom for nuclear medicine studies.

Dynamic radionuclide renal study (renography) provides functional and structural information of the kidney and urinary tract noninvasively. Our purpose in this study is to describe the construction and test results of a dynamic renal phantom with different clinical features of radionuclide renography. The phantom consisted of five pieces of different shaped Plexiglas boxes: Two kidneys, one liver, two square shaped boxes (one heart and one bladder). The bladder was internally divided into two compartments in order to collect each kidney output separately. The dynamic circulation of the phantom was maintained under a hydrostatic pressure approximately equal to 13.3 kPa (average human blood pressure). The standard dose distribution among different organs and different renographic parameters were calculated from series of normal patients study (91 with 99mTc-DTPA, 68 with 99mTc-EC). All the studies were performed with same camera (Siemens Orbiter Digitrac 7500) equipped with LEAP (low energy all purpose) collimator using ADAC Pegasys II analytic package program under the same clinical procedure. Different regions of interest (ROIs) were drawn for concerning organs and counts per second (CPS) were collected for each ROI. The series of renogram curves were generated by phantom-studies with different flow rates for left kidney (LK) and right kidney (RK). The renal index (RI) for an individual study was calculated as the product of two indexes: "Relative Renal Function" (RRF) (water-volume of LK/RK) and "Relative Renal Time" (RRT) (Tmax of LK/RK). The most significant correlation was found in total CPS for LK and RK between the EC group and phantom studies (p < 0.001). The calculated RI values were used to simulate the patients' study with different clinical features. The dynamics were found reproducible. The phantom is suitable for using in calibration and quality control protocols of the renogram procedure used in Nuclear Medicine.

Adolescent↗

[Three-dimensional fusion imaging of lymphoscintigraphy and MDCT for sentinel node biopsy in breast cancer].

The purpose of this study was to evaluate the clinical usefulness of three-dimensional (3D) fusion imaging of lymphoscintigraphy with 99mTc phytate and MDCT (four-slice CT) for sentinel node biopsy in breast cancer. Volume-rendering images generated by MDCT were fused with lymphoscintigrams on a personal computer. The subjects were 7 patients with clinically negative nodes. In all patients, sentinel nodes were identified by lymphoscintigraphy, and the anatomical locations of sentinel nodes were clearly demonstrated by 3D-fusion imaging. 3D-fusion imaging of lymphoscintigraphy and MDCT is expected to be a promising method for sentinel node biopsy in breast cancer.

Breast Neoplasms↗

Noninvasive rCBF determination by 133XE-inhalation with the gamma camera and functional imaging of wash-in and wash-out. A new combined approach for rCBE measurements in patients with cerebrovascular disease.

In 47 patients with cerebrovascular disease (CVD) a noninvasive determination of global and regional cerebral blood flow (CBF) was performed with the gamma camera. A new approach was developed for region definition and for evaluation of the "start-fit-time' as the point of minimal contamination of the recorded data by extracerebral scatter and recirculation using the region of interest (ROI)-technique in the camera field of view. In comparison with the results of probe measurement of end-tidal exhalation air no significant differences were seen and values obtained were well in the range reported by other authors. Initial slope (IS), gray matter flow (F1) and CBF-15 were used as quantitative parameters and were able to distinguish significantly (P less than 0.01) between normals, patients with mild CVD, and severe CVD. Intraexamination variation coefficient (VC) was 5%, interexamination VC was 8%. Functional, parametric images of wash-in for easier ROI-definition and judgement of isotope supply and of wash-out were generated by a computer analysis and were found to be sensitive indicators for arterial blood supply and wash-out values city. Thus it was possible to recalculate regional flow values in focal areas exactly corresponding to abnormalities seen on the functional images. So the regional information of functional images can be combined with the quantitative data in selectable areas. By tis noninvasive, easily performed method focal neurological deficits can be evaluated with high accuracy with conventional nucleus medicine equipment.

Cerebrovascular Circulation↗

Macrophage targeting with technetium-99m labelled J001 acylated poly-galactoside for scintigraphy of inflammation: optimization and assessment of imaging specificity in experimental arthritis.

J001, an acylated poly-(1,3)-galactoside purified from the membrane of Klebsiella pneumoniae, associates selectively with macrophages via the binding to CD11b and CD14 molecules. Inflammatory foci known to recruit macrophages could thus be imaged with technetium-99m labelled J001. This study aims to define the optimal scintigraphic protocol for 99mTc-J001 imaging and to evaluate the specificity of J001 scans. A dose range study was conducted in rabbits with immunological arthritis using six different specific activities ranging from 370 to 11840 MBq&middot;mg-1 while the intravenously injected activity was constant (37 MBq) Radiochemical purity for each preparation was documented together with the in vivo stability of the 99mTc-J001 complex using exclusion-diffusion radioHPLC of serum collected 1 h after radiopharmaceutical administration. Scintigraphic images were recorded at 2, 3 and 4h and analysed using indexes calculated from regions of interest. Specificity of the macrophage imaging was assessed by comparison with scans obtained after administration of 99mTcO4(- )or 99mTc-albumin nanocolloids. A protocol of plasma transfusion was also used to inject 99mTc-J001 after complete removal of radioactive colloids likely to be generated during the labelling. For the higher specific activities (5920 and 11840 MBq.mg-1), radiochemical purity degradation and in vitro 99mTc transchelation were noted. To prevent transchelation and 99mTc bond hydrolysis likely to impair imaging specificity, 1480 MBq.mg-1 corresponding to 25microg injected J001 was found to be the optimal usable specific activity. Results obtained with the various tracers support the hypothesis that macrophage targeting is the main factor involved in the J001 imaging of arthritis.

Animals↗

The clinical value of quantitative dynamic scintigraphy in salivary gland disorders.

Salivary gland scintigraphy with [99mTc]pertechnetate was performed in a group of 11 subjects without any known salivary pathology, and in a group of 12 xerostomic patients. Time-activity curves, normalized to background, were generated for each of the four major salivary glands in both groups, and averaged into single curves, representing the function of each gland. Comparing the two sets of curves (patients vs controls) demonstrates that utilizing our "normalization" approach enables one not only to determine whether one group of dynamic curves is significantly different from another, but to decide which of the glands are normal and which are malfunctioning. The sensitivity, specificity, accuracy and predictive values of this procedure are all above 0.90.

Adult↗

Novel 99mTc radiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit.

A quinazolinone derivative as a novel non-peptidic CCK-B receptor antagonist designated as Qn-In, was synthesized, characterized by spectroscopic techniques and evaluated for radiopharmaceutical potential. The efficiency of labeling with (99m)Tc was greater than 98% and the complex was stable for about 7 hours at 37 degrees C in presence of serum. Affinity of Qn-In was determined to be in nanomolar range by competitive binding studies on cancer cell line MDA-MB-468. Bio-distribution of (99m)Tc labeled Qn-In in mice was examined by intravenous administration and time-activity curves were generated. The ligand showed binding to most of the organs, known to express CCK-B receptor. The lack of uptake in brain may be due to the inability of the complex to cross the blood-brain barrier. Our results show that (99m)Tc labeled Qn-In ligand provides a new template for further development of non-peptidic ligands for diagnosis and therapy of diseases related with CCK-B receptor.

Animals↗

Localization of I-131-labeled goat and primate anti-carcinoembryonic antigen(CEA) antibodies in patients with cancer.

Thirty patients with anti-carcinoembryonic antigen (CEA)-producing cancers of the colon, breast, or thyroid were injected with 1 to 2 mCi of Iodine-131 (131I)-labeled, affinity-purified, goat or baboon anti-CEA antibodies. Images were obtained daily for four days. Computerized background subtraction using technetium 99m (99mTC)-labeled compounds was used. Images obtained with and without background subtraction were correlated with other evidence of disease. Activity levels in plasma, urine, and thyroid gland were monitored. Significant deiodination of antibody occurred within the first 24 hours. The mean plasma half-disappearance-time of baboon antibody was significantly longer than the mean half-disappearance-time of goat antibody. With exogenous blockade, total thyroid uptake was less than 0.1% of the injected dose. Without background subtraction, scintigraphic localization of known tumor was possible in one of two patients with colon carcinoma, in three of 20 patients with breast cancer, and in one of five patients with medullary carcinoma of the thyroid. With background subtraction, potential false-positive results could be generated for every patients, depending on the normalization site chosen and the degree of subtraction used. In contrast to results of previous reports, CEA-producing tumor was found to be infrequently localized using highly purified goat or primate radiolabeled anti-CEA. Furthermore, the subtraction technique described by previous investigators may lead to a high false-positive rate.

Adolescent↗

Rubidium-82 generators for imaging studies.

Strontium-82, produced by spallation reaction with medium-energy proton beams, was used to evaluate Bio-Rex 70 and Chelex-100 ion-exchange resins for use in a compact Rb-82 generator. Adsorption of Sr-82 to the resin column, Rb-82 elution yields, Sr breakthrough, and 82Rb-Sr separation factors were determined for newly prepared columns and for longterm elution conditions. Separation factors of 10(7) to 10(8) were obtained with 2% NaCl elutions from Bio-Rex 70 resin columns while the separation factors was about 5 X 10(4) with the Chelex-100 resin column.

Evaluation Studies as Topic↗

Effect of 360 degrees and 180 degrees rotation SPET acquisitions on myocardial polar map: comparison of 201Tl-, 99Tcm- and 123I-labelled radiopharmaceuticals.

Both 360 degrees and 180 degrees rotation acquisition methods have been used in myocardial single photon emission tomography (SPET) studies. We compared both methods using 201Tl, 99Tcm and 123I radiopharmaceuticals with phantoms and clinical models. Myocardial phantom studies with anterior and inferior defects were performed using 201Tl, 99Tcm and 123I. Clinical models of 14 typical situations, including normal subjects, patients with anterior or inferior defects and a high right hemi-diaphragm, were studied. The radiopharmaceuticals were 201Tl, 99Tcm-sestamibi, 123I-BMIPP and 123I-MIBG. Four sets of 180 degrees anterior rotation data with starting angles of (A) posterior, (B) LPO 30 degrees, (C) LPO 60 degrees and (D) left lateral direction were generated and compared with 360 degrees rotation SPET. A polar map display was used for quantification. In phantom studies, the defect contrast on the map was higher in the anterior defect with 180 degrees rotation than with 360 degrees rotation. However, it was decreased in the inferior defect, particularly with 201Tl, because of decreased wall activity around the defect. In the patient model with anterior or inferior defects, the defect contrast was improved with 180 degrees SPET by up to 10%. A slight decrease in the normal region was also noted in the 180 degrees reconstruction. The effect of diffuse liver activity on the inferior region depended on the rotation range. A patient with a high right hemi-diaphragm showed a lower inferior count with 360 degrees SPET. In conclusion, the 360 degrees acquisition was superior to the 180 degrees acquisition in the phantom with defects. Clinically, the quantitative differences in radionuclide types (99Tcm, 123I or 201Tl) were not significant for quantifying a moderate degree (50-60% of peak count) of defect. However, we note quantitative variation depending on the rotation range in the 180 degrees method.

3-Iodobenzylguanidine↗

One brain, two selves.

Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with Multiple Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory. Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.

Adult↗

Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics.

UNLABELLED: The alpha(v)beta3 integrin plays an important role in metastasis and tumor-induced angiogenesis. Targeting with radiolabeled ligands of the alpha(v)beta3 integrin may provide information about the receptor status and enable specific therapeutic planning. Previous studies from our group resulted in tracers that showed alpha(v)beta3-selective tumor uptake. However, these first-generation compounds predominantly revealed hepatobiliary excretion with high radioactivity found in the liver. In this report, the synthesis and biological evaluation of the first glycosylated RGD-containing peptide (RGD-peptide) for the noninvasive imaging of alpha(v)beta3 expression are described. METHODS: Peptides were assembled on a solid support using fluorenylmethoxycarbonyl-coupling protocols. The precursor cyclo(-Arg-Gly-Asp-D-Tyr-Lys(SAA)-) GP1 was synthesized by coupling 3-acetamido-2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-beta-D-glycero-D-gulo-heptonic acid (SAA(Bn3)) with cyclo(-Arg(Mtr)-Gly-Asp(OtBu)-D-Tyr(tBu)-Lys-) and subsequent removal of the protection groups. Iodine labeling was performed by the Iodo-Gen method (radiochemical yield > 50%). The in vitro binding assays were performed using purified immobilized alpha(IIb)beta3, alpha(v)beta5, and alpha(v)beta3 integrins. For in vivo experiments, nude mice bearing xenotransplanted melanomas and mice with osteosarcomas were used. RESULTS: The glycosylated peptide 3-iodo-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Lys(SAA)-) GP2 showed high affinity and selectivity for alpha(v)beta3 in vitro (50% inhibitory concentration = 40 nmol/L). Pretreatment studies indicate specific binding of [125I]GP2 on alpha(v)beta3-expressing tumors in vivo. Comparison of the pharmacokinetics of [125I]GP2 and [125I]-3-iodo-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val-) [125I]P2 revealed for [125I]GP2 an increased activity concentration in the blood (e.g., 3.59 +/- 0.35 percentage injected dose [%ID]/g vs. 1.72 +/- 0.44 %ID/g at 10 min postinjection) and a significantly reduced uptake in the liver (e.g., 2.59 +/- 0.24 %ID/g vs. 21.96 +/- 2.78 %ID/g at 10 min postinjection). Furthermore, a clearly increased activity accumulation in the tumor was found (e.g., 3.05 +/- 0.31 %ID/g vs. 0.92 +/- 0.16 %ID/g at 240 min postinjection), which remained almost constant between 60 and 240 min postinjection. This resulted in good tumor-to-organ ratios for the glycosylated tracer (e.g., 240-min postinjection osteosarcoma model: tumor-to-blood = 16; tumor-to-muscle = 7; tumor-to-liver = 2.5), which were confirmed by the first gamma-camera images of osteosarcoma-bearing mice at 240 min postinjection. CONCLUSION: This study demonstrates that the introduction of a sugar moiety improves the pharmakokinetic behavior of a hydrophobic peptide-based tracer. Additionally, this alpha(v)beta3-selective glycosylated radioiodinated second-generation tracer GP2 shows high tumor uptake and good tumor-to-organ ratios that allow noninvasive visualization of alpha(v)beta3-expressing tumors and monitoring therapy with alpha(v)beta3 antagonists. Finally, the favorable biokinetics make the glycosylated RGD-peptide a promising lead structure for tracers to quantify the alpha(v)beta3 expression using PET.

Animals↗

Pretreatment of animal wastes containing radioisotopes with dry-distillation.

Mice that had been radiolabeled with one of seven isotopes by intraperitoneal or subcutaneous administration were dry-distilled at 800 degrees C for 10 min, and the fate of the radionuclide was examined. The radionuclides administered were 3H, 14C, 32P, 35S, 45Ca, 51Cr, and 125I, all of which are commonly used in animal experiments. After dry-distillation, 95% of 3H was found in the distillate (condensate), and 80% and 16% of 14C were recovered from exhaust gas and residual solids, respectively. Only between 10 and 20% of 35S was found in distillate. The remainder of the residual 35S was recovered from the inner wall of the exhaust vent of the dry-distillation equipment. About 24% of 125I was also recovered from the inner wall of this same exhaust vent, and the residual radioactive materials were recovered from the residual solids. On the other hand, 32P, 45Ca, and 51Cr were recovered entirely from the residual solids. The weight of the animals decreased to about 10%, and the volume to about 20% (mice and rats) to 40% (rabbits) after dry-distillation. The residual solids of animal wastes generated by dry-distillation were odorless and chemically and biologically stable. Dry-distillation has many merits as a pretreatment for the disposal of animal wastes containing radioactive material because of the easy handling, storage, and transportation of the residual solids.

Animals↗

Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.

The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered.

Administration, Inhalation↗