Multifield and inverse-contrast switching of magnetocaloric high contrast ratio MRI labels.

PURPOSE: Demonstrating multifield and inverse contrast switching of magnetocaloric high contrast ratio MRI labels that either have increasing or decreasing moment versus temperature slopes depending on the material at physiological temperatures and different MRI magnetic field strengths. METHODS: Two iron-rhodium samples of different purity (99% and 99.9%) and a lanthanum-iron-silicon sample were obtained from commercial vendors. Temperature and magnetic field-dependent magnetic moment measurements of the samples were performed on a vibrating sample magnetometer. Temperature-dependent MRI of different iron-rhodium and lanthanum-iron-silicon samples were performed on 3 different MRI scanners at 1 Tesla (T), 4.7T, and 7T. RESULTS: Sharp, first-order magnetic phase transition of each iron-rhodium sample at a physiologically relevant temperature (~37°C) but at different MRI magnetic fields (1T, 4.7T, and 7T, depending on the sample) showed clear image contrast changes in temperature-dependent MRI. Iron-rhodium and lanthanum-iron-silicon samples with sharp, first-order magnetic phase transitions at the same MRI field of 1T and physiological temperature of 37°C, but with positive and negative slope of magnetization versus temperature, respectively, showed clear inverse contrast image changes. Temperature-dependent MRI on individual microparticle samples of lanthanum-iron-silicon also showed sharp image contrast changes. CONCLUSION: Magnetocaloric materials of different purity and composition were demonstrated to act as diverse high contrast ratio switchable MRI contrast agents. Thus, we show that a range of magnetocaloric materials can be optimized for unique image contrast response under MRI-appropriate conditions at physiological temperatures and be controllably switched in situ.

Nanoparticle-Peptide-Drug Bioconjugates for Unassisted Defeat of Multidrug Resistance in a Model Cancer Cell Line.

Multidrug resistance (MDR) is a significant challenge in the treatment of many types of cancers as membrane-associated transporters actively pump drugs out of the cell, limiting therapeutic efficacy. While nanoparticle (NP)-based therapeutics have emerged as a mechanism for overcoming MDR, they often rely on the delivery of multiple anticancer drugs, nucleic acid hybrids, or MDR pump inhibitors. The effectiveness of these strategies, however, can be limited by their off-target toxicity or the need for genetic transfection. In this paper, we describe a NP-peptide-drug bioconjugate that achieves significant cell killing in MDR-positive cancer cells without the need for additional drugs. We use a quantum dot (QD) as a central scaffold to append two species of peptide, a cell-uptake peptide to facilitate endocytic internalization and a peptide-drug conjugate that is susceptible to cleavage by esterases found within the endocytic pathway. This approach relies on spatiotemporal control over drug release, where endosomes traffic drug away from membrane-resident pumps and release it closer to the nucleus. Cellular internalization studies showed high uptake of the NP-drug complex and nuclear localization of the drug after 48 h in MDR-positive cells. Additionally, cellular proliferation assays demonstrated a 40% decrease in cell viability for the NP-drug bioconjugate compared to free drug, confirming the utility of this system in overcoming MDR in cancer cells.

Intracellularly Actuated Quantum Dot-Peptide-Doxorubicin Nanobioconjugates for Controlled Drug Delivery via the Endocytic Pathway.

Nanoparticle (NP)-mediated drug delivery (NMDD) has emerged as a novel method to overcome the limitations of traditional systemic delivery of therapeutics, including the controlled release of the NP-associated drug cargo. Currently, our most advanced understanding of how to control NP-associated cargos is in the context of soft nanoparticles (e.g., liposomes), but less is known about controlling the release of cargos from the surface of hard NPs (e.g., gold NPs). Here we employ a semiconductor quantum dot (QD) as a prototypical hard NP platform and use intracellularly triggered actuation to achieve spatiotemporal control of drug release and modulation of drug efficacy. Conjugated to the QD are two peptides: (1) a cell-penetrating peptide (CPP) that facilitates uptake of the conjugate into the endocytic pathway and (2) a display peptide conjugated to doxorubicin (DOX) via three different linkages (ester, disulfide, and hydrazone) that are responsive to enzymatic cleavage, reducing conditions, and low pH, respectively. Formation of the QD-[peptide-DOX]-CPP complex is driven by self-assembly that allows control over both the ratio of each peptide species conjugated to the QD and the eventual drug dose delivered to cells. Förster resonance energy transfer assays confirmed successful assembly of the QD-peptide complexes and functionality of the linkages. Confocal microscopy was employed to visualize residence of the QD-[peptide-DOX]-CPP complexes in the endocytic pathway, and distinct differences in DOX localization were noted for the ester linkage, which showed clear signs of nuclear delivery versus the hydrazone, disulfide, and amide control. Finally, delivery of the QD-[peptide-DOX]-CPP conjugate resulted in cytotoxicity for the ester linkage that was comparable to free DOX. Attachment of DOX via the hydrazone linkage facilitated intermediary toxicity, while the disulfide and amide control linkages showed minimal toxicity. Our data demonstrate the utility of hard NP-peptide bioconjugates to function as multifunctional scaffolds for simultaneous control over cellular drug uptake and toxicity and the vital role played by the nature of the chemical linkage that appends the drug to the NP carrier.

Concurrent Modulation of Quantum Dot Photoluminescence Using a Combination of Charge Transfer and Förster Resonance Energy Transfer: Competitive Quenching and Multiplexed Biosensing Modality.

An emerging trend with semiconductor quantum dots (QDs) is their use as scaffolds to assemble multiple energy transfer pathways. Examples to date have combined various competitive and sequential Förster resonance energy transfer (FRET) pathways between QDs and fluorescent dyes, luminescent lanthanide complexes, and bioluminescent proteins. Here, we show that the photoluminescence (PL) of QD bioconjugates can also be modulated by a combination of FRET and charge transfer (CT), and characterize the concurrent effects of these mechanistically different pathways using PL measurements at both the ensemble and the single particle level. Peptides were distally labeled with either a fluorescent dye that quenched QD PL through FRET or a ruthenium(II) phenanthroline complex that quenched QD PL through electron transfer. The labeled peptides were assembled around a central CdSe/ZnS QD at different ratios, tuning the relative rates of FRET and CT, which were competitive quenching pathways. The concurrent effects of FRET and CT were predictable from a rate analysis that was calibrated to the isolated effects of each of these pathways. Notably, the dye/QD PL intensity ratio reflected changes in the relative rate of FRET but was approximately independent of CT. In turn, the sum of the QD and dye PL intensities, when adjusted for quantum yields, reflected changes in the relative rate of CT quenching, approximately independent of FRET. The capacity for multiplexed sensing of protease activity was demonstrated using these two orthogonal detection channels. Combined CT-FRET configurations with QDs are thus promising for applications in bioanalysis, sensing, and imaging, and may prove useful in other photonic applications.

Quantum dot-based multiphoton fluorescent pipettes for targeted neuronal electrophysiology.

Targeting visually identified neurons for electrophysiological recording is a fundamental neuroscience technique; however, its potential is hampered by poor visualization of pipette tips in deep brain tissue. We describe quantum dot-coated glass pipettes that provide strong two-photon contrast at deeper penetration depths than those achievable with current methods. We demonstrated the pipettes' utility in targeted patch-clamp recording experiments and single-cell electroporation of identified rat and mouse neurons in vitro and in vivo.

Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes.

The intrinsic properties of quantum dots (QDs) and the growing ability to interface them controllably with living cells has far-reaching potential applications in probing cellular processes such as membrane action potential. We demonstrate that an electric field typical of those found in neuronal membranes results in suppression of the QD photoluminescence (PL) and, for the first time, that QD PL is able to track the action potential profile of a firing neuron with millisecond time resolution. This effect is shown to be connected with electric-field-driven QD ionization and consequent QD PL quenching, in contradiction with conventional wisdom that suppression of the QD PL is attributable to the quantum confined Stark effect.

Optimizing protein coordination to quantum dots with designer peptidyl linkers.

Semiconductor quantum dots (QDs) demonstrate select optical properties that make them of particular use in biological imaging and biosensing. Controlled attachment of biomolecules such as proteins to the QD surface is thus critically necessary for development of these functional nanobiomaterials. QD surface coatings such as poly(ethylene glycol) impart colloidal stability to the QDs, making them usable in physiological environments, but can impede attachment of proteins due to steric interactions. While this problem is being partially addressed through the development of more compact QD ligands, here we present an alternative and complementary approach to this issue by engineering rigid peptidyl linkers that can be appended onto almost all expressed proteins. The linkers are specifically designed to extend a terminal polyhistidine sequence out from the globular protein structure and penetrate the QD ligand coating to enhance binding by metal-affinity driven coordination. α-Helical linkers of two lengths terminating in either a single or triple hexahistidine motif were fused onto a single-domain antibody; these were then self-assembled onto QDs to create a model immunosensor system targeted against the biothreat agent ricin. We utilized this system to systematically evaluate the peptidyl linker design in functional assays using QDs stabilized with four different types of coating ligands including poly(ethylene glycol). We show that increased linker length, but surprisingly not added histidines, can improve protein to QD attachment and sensor performance despite the surface ligand size with both custom and commercial QD preparations. Implications for these findings on the development of QD-based biosensors are discussed.

Quantum dots as simultaneous acceptors and donors in time-gated Förster resonance energy transfer relays: characterization and biosensing.

The unique photophysical properties of semiconductor quantum dot (QD) bioconjugates offer many advantages for active sensing, imaging, and optical diagnostics. In particular, QDs have been widely adopted as either donors or acceptors in Förster resonance energy transfer (FRET)-based assays and biosensors. Here, we expand their utility by demonstrating that QDs can function in a simultaneous role as acceptors and donors within time-gated FRET relays. To achieve this configuration, the QD was used as a central nanoplatform and coassembled with peptides or oligonucleotides that were labeled with either a long lifetime luminescent terbium(III) complex (Tb) or a fluorescent dye, Alexa Fluor 647 (A647). Within the FRET relay, the QD served as a critical intermediary where (1) an excited-state Tb donor transferred energy to the ground-state QD following a suitable microsecond delay and (2) the QD subsequently transferred that energy to an A647 acceptor. A detailed photophysical analysis was undertaken for each step of the FRET relay. The assembly of increasing ratios of Tb/QD was found to linearly increase the magnitude of the FRET-sensitized time-gated QD photoluminescence intensity. Importantly, the Tb was found to sensitize the subsequent QD-A647 donor-acceptor FRET pair without significantly affecting the intrinsic energy transfer efficiency within the second step in the relay. The utility of incorporating QDs into this type of time-gated energy transfer configuration was demonstrated in prototypical bioassays for monitoring protease activity and nucleic acid hybridization; the latter included a dual target format where each orthogonal FRET step transduced a separate binding event. Potential benefits of this time-gated FRET approach include: eliminating background fluorescence, accessing two approximately independent FRET mechanisms in a single QD-bioconjugate, and multiplexed biosensing based on spectrotemporal resolution of QD-FRET without requiring multiple colors of QD.

Spectral characterization of biological aerosol particles using two-wavelength excited laser-induced fluorescence and elastic scattering measurements.

A two-wavelength laser-induced fluorescence (LIF) instrument has been developed and used to characterize individual biological aerosol particles, including biological warfare (BW) agent surrogates. Fluorescence in discrete spectral bands from widely different species, and also from similar species under different growth conditions were measured and compared. The two-wavelength excitation approach was found to increase discrimination among several biological materials, and especially with respect to diesel exhaust particles, a common interferent for LIF BW detection systems. The spectral characteristics of a variety of biological materials and ambient air components have been studied as a function of aerosol particle size and incident fluence.

Characterization of a gated fiber-optic-coupled detector for application in clinical electron beam dosimetry.

PURPOSE: Assessment of the fundamental dosimetric characteristics of a novel gated fiber-optic-coupled dosimetry system for clinical electron beam irradiation. METHODS: The response of fiber-optic-coupled dosimetry system to clinical electron beam, with nominal energy range of 6-20 MeV, was evaluated for reproducibility, linearity, and output dependence on dose rate, dose per pulse, energy, and field size. The validity of the detector system's response was assessed in correspondence with a reference ionization chamber. RESULTS: The fiber-optic-coupled dosimetry system showed little dependence to dose rate variations (coefficient of variation +/- 0.37%) and dose per pulse changes (with 0.54% of reference chamber measurements). The reproducibility of the system was +/- 0.55% for dose fractions of approximately 100 cGy. Energy dependence was within +/- 1.67% relative to the reference ionization chamber for the 6-20 MeV nominal electron beam energy range. The system exhibited excellent linear response (R2 = 1.000) compared to reference ionization chamber in the dose range of 1-1000 cGy. The output factors were within +/- 0.54% of the corresponding reference ionization chamber measurements. CONCLUSIONS: The dosimetric properties of the gated fiber-optic-coupled dosimetry system compare favorably to the corresponding reference ionization chamber measurements and show considerable potential for applications in clinical electron beam radiotherapy.

Nanoparticle-Mediated Visualization and Control of Cellular Membrane Potential: Strategies, Progress, and Remaining Issues.

The interfacing of nanoparticle (NP) materials with cells, tissues, and organisms for a range of applications including imaging, sensing, and drug delivery continues at a rampant pace. An emerging theme in this area is the use of NPs and nanostructured surfaces for the imaging and/or control of cellular membrane potential (MP). Given the important role that MP plays in cellular biology, both in normal physiology and in disease, new materials and methods are continually being developed to probe the activity of electrically excitable cells such as neurons and muscle cells. In this Review, we highlight the current state of the art for both the visualization and control of MP using traditional materials and techniques, discuss the advantageous features of NPs for performing these functions, and present recent examples from the literature of how NP materials have been implemented for the visualization and control of the activity of electrically excitable cells. We conclude with a forward-looking perspective of how we expect to see this field progress in the near term and further into the future.

Classification and selective collection of individual aerosol particles using laser-induced fluorescence.

We describe the development and performance evaluation of a system for optical interrogation, subsequent selection, and collection of individual aerosol particles entrained in an inlet air stream. Elastic scatter and laser-induced fluorescence obtained from single particles on-the-fly provide compositional information for classification criteria. Individual particles could then be selectively electrically charged and captured to a conductive substrate with an electric potential. The optical subsystem also includes a novel two-beam velocimeter to provide accurate downstream timing. Good overall quantitative performance values are reported for particles in the size range of 1-8 microm at mean rates up to 4 kHz.

Cholesterol Functionalization of Gold Nanoparticles Enhances Photoactivation of Neural Activity.

Gold nanoparticles (AuNPs) attached to the extracellular leaflet of the plasma membrane of neurons can enable the generation of action potentials (APs) in response to brief pulses of light. Recently described techniques to stably bind AuNP bioconjugates directly to membrane proteins (ion channels) in neurons enable robust AP generation mediated by the photoexcited conjugate. However, a strategy that binds the AuNP to the plasma membrane in a non protein-specific manner could represent a simple, single-step means of establishing light-responsiveness in multiple types of excitable neurons contained in the same tissue. On the basis of the ability of cholesterol to insert into the plasma membrane, here we test whether AuNP functionalization with linear dihydrolipoic acid-poly(ethylene) glycol (DHLA-PEG) chains that are distally terminated with cholesterol (AuNP-PEG-Chol) can enable light-induced AP generation in neurons. Dorsal root ganglion (DRG) neurons of rat were labeled with 20 nm diameter spherical AuNP-PEG-Chol conjugates wherein ∼30% of the surface ligands (DHLA-PEG-COOH) were conjugated to PEG-Chol. Voltage recordings under current-clamp conditions showed that DRG neurons labeled in this manner exhibited a capacity for AP generation in response to microsecond and millisecond pulses of 532 nm light, a property attributable to the close tethering of AuNP-PEG-Chol conjugates to the plasma membrane facilitated by the cholesterol moiety. Light-induced AP and subthreshold depolarizing responses of the DRG neurons were similar to those previously described for AuNP conjugates targeted to channel proteins using large, multicomponent immunoconjugates. This likely reflected the AuNP-PEG-Chol's ability, upon plasmonic light absorption and resultant slight and rapid heating of the plasma membrane, to induce a concomitant transmembrane depolarizing capacitive current. Notably, AuNP-PEG-Chol delivered to DRG neurons by inclusion in the buffer contained in the recording pipet/electrode enabled similar light-responsiveness, consistent with the activity of AuNP-PEG-Chol bound to the inner (cytofacial) leaflet of the plasma membrane. Our results demonstrate the ability of AuNP-PEG-Chol conjugates to confer timely stable and direct responsiveness to light in neurons. Further, this strategy represents a general approach for establishing excitable cell photosensitivity that could be of substantial advantage for exploring a given tissue's suitability for AuNP-mediated photocontrol of neural activity.

Evaluating the potential of using quantum dots for monitoring electrical signals in neurons.

Success in the projects aimed at providing an advanced understanding of the brain is directly predicated on making critical advances in nanotechnology. This Perspective addresses the unique interface of neuroscience and nanomaterials by considering the foundational problem of sensing neuron membrane voltage and offers a potential solution that may be facilitated by a prototypical nanomaterial. Despite substantial improvements, the visualization of instantaneous voltage changes within individual neurons, whether in cell culture or in vivo, at both the single-cell and network level at high speed remains complex and problematic. The unique properties of semiconductor quantum dots (QDs) have made them powerful fluorophores for bioimaging. What is not widely appreciated, however, is that QD photoluminescence is exquisitely sensitive to proximal electric fields. This property should be suitable for sensing voltage changes that occur in the active neuronal membrane. Here, we examine the potential role of QDs in addressing the important challenge of real-time optical voltage imaging.

Characterization of a fiber-optic-coupled radioluminescent detector for application in the mammography energy range.

Fiber-optic-coupled radioluminescent (FOC) dosimeters are members of a new family of dosimeters that are finding increased clinical applications. This study provides the first characterization of a Cu doped quartz FOC dosimeter at diagnostic energies, specifically across the range of x-ray energies and intensities used in mammographies. We characterize the calibration factors, linearity, angular dependence, and reproducibility of the FOC dosimeters. The sensitive element of each dosimeter was coupled to a photon counting photomultiplier module via 1 m long optical fibers. A computer controlled interface permitted real-time monitoring of the dosimeter output and rapid data acquisition. The axial-angular responses for all dosimeter models show nearly uniform response without any marked decrease in sensitivity. However, the normal-to-axial angular response showed a marked decrease in sensitivity of about 0 degrees C and 180 degrees C. In most clinical applications, appropriate dosimeter positioning can minimize the contributions of the varying normal-to-axial response. The FOC dosimeters having the greatest sensitive length provided the greatest sensitivity, with greatest to lowest sensitivity observed for 4.0, 1.9, 1.6, and 1.1 mm length sensitive elements. The average sensitivity of the dosimeters varies linearly with sensitive volume (R2=95%) and as a function of tube potential and target/filter combinations, generally exhibiting an increased sensitivity for higher energies. The dosimeter sensitivity as a function of tube potential had an average increase of 4.72 +/- 2.04% for dosimeter models and three target-filter combinations tested (Mo/Mo, Mo/Rh, and Rh/Rh) over a range of 25-31 kVp. All dosimeter models exhibited a linear response (R2 > or = 0.997) to exposure for all target-filter combinations, tube potentials, and tube current-time product stations evaluated and demonstrated reproducibility within 2%. All of the dosimeters examined in this study provided a response adequate for the accurate measurement of doses in clinical mammography applications.

Bridging Lanthanide to Quantum Dot Energy Transfer with a Short-Lifetime Organic Dye.

Semiconductor nanocrystals or quantum dots (QDs) should act as excellent Förster resonance energy transfer (FRET) acceptors due to their large absorption cross section, tunable emission, and high quantum yields. Engaging this type of FRET can be complicated due to direct excitation of the QD acceptor along with its longer excited-state lifetime. Many cases of QDs acting as energy transfer acceptors are within time-gated FRET from long-lifetime lanthanides, which allow the QDs to decay before observing FRET. Efficient QD sensitization requires the lanthanide to be in close proximity to the QD. To overcome the lifetime mismatch issues and limited transfer range, we utilized a Cy3 dye to bridge the energy transfer from an extremely long lived terbium emitter to the QD. We demonstrated that short-lifetime dyes can be used as energy transfer relays between extended lifetime components and in this way increased the distance of terbium-QD FRET to ∼14 nm.

Quantum Dot-Peptide-Fullerene Bioconjugates for Visualization of in Vitro and in Vivo Cellular Membrane Potential.

We report the development of a quantum dot (QD)-peptide-fullerene (C60) electron transfer (ET)-based nanobioconjugate for the visualization of membrane potential in living cells. The bioconjugate is composed of (1) a central QD electron donor, (2) a membrane-inserting peptidyl linker, and (3) a C60 electron acceptor. The photoexcited QD donor engages in ET with the C60 acceptor, resulting in quenching of QD photoluminescence (PL) that tracks positively with the number of C60 moieties arrayed around the QD. The nature of the QD-capping ligand also modulates the quenching efficiency; a neutral ligand coating facilitates greater QD quenching than a negatively charged carboxylated ligand. Steady-state photophysical characterization confirms an ET-driven process between the donor-acceptor pair. When introduced to cells, the amphiphilic QD-peptide-C60 bioconjugate labels the plasma membrane by insertion of the peptide-C60 portion into the hydrophobic bilayer, while the hydrophilic QD sits on the exofacial side of the membrane. Depolarization of cellular membrane potential augments the ET process, which is manifested as further quenching of QD PL. We demonstrate in HeLa cells, PC12 cells, and primary cortical neurons significant QD PL quenching (ΔF/F0 of 2-20% depending on the QD-C60 separation distance) in response to membrane depolarization with KCl. Further, we show the ability to use the QD-peptide-C60 probe in combination with conventional voltage-sensitive dyes (VSDs) for simultaneous two-channel imaging of membrane potential. In in vivo imaging of cortical electrical stimulation, the optical response of the optimal QD-peptide-C60 configuration exhibits temporal responsivity to electrical stimulation similar to that of VSDs. Notably, however, the QD-peptide-C60 construct displays 20- to 40-fold greater ΔF/F0 than VSDs. The tractable nature of the QD-peptide-C60 system offers the advantages of ease of assembly, large ΔF/F0, enhanced photostability, and high throughput without the need for complicated organic synthesis or genetic engineering, respectively, that is required of traditional VSDs and fluorescent protein constructs.

Elimination of Cerenkov interference in a fibre-optic-coupled radiation dosemeter.

An optical fibre point dosemeter based on the gated detection of the luminescence from a Cu(1+)-doped fused quartz detector effectively eliminated errors due to Cerenkov radiation and native fibre fluorescence. The gated optical fibre dosemeter overcomes serious problems faced by scintillation and optically stimulated luminescence approaches to optical fibre point dosimetry. The dosemeter was tested using an external beam radiotherapy machine that provided pulses of 6 MV X rays. Gated detection was used to discriminate the signal collected during the radiation pulses, which included contributions from Cerenkov radiation and native fibre fluorescence, from the signal collected between the radiation pulses, which contained only the long-lived luminescence from the Cu(1+)-doped fused quartz detector. Gated detection of the luminescence provided accurate, real-time dose measurements that were linear with absorbed dose, independent of dose rate and that were accurate for all field sizes studied.

Energy Transfer Sensitization of Luminescent Gold Nanoclusters: More than Just the Classical Förster Mechanism.

Luminescent gold nanocrystals (AuNCs) are a recently-developed material with potential optic, electronic and biological applications. They also demonstrate energy transfer (ET) acceptor/sensitization properties which have been ascribed to Förster resonance energy transfer (FRET) and, to a lesser extent, nanosurface energy transfer (NSET). Here, we investigate AuNC acceptor interactions with three structurally/functionally-distinct donor classes including organic dyes, metal chelates and semiconductor quantum dots (QDs). Donor quenching was observed for every donor-acceptor pair although AuNC sensitization was only observed from metal-chelates and QDs. FRET theory dramatically underestimated the observed energy transfer while NSET-based damping models provided better fits but could not reproduce the experimental data. We consider additional factors including AuNC magnetic dipoles, density of excited-states, dephasing time, and enhanced intersystem crossing that can also influence ET. Cumulatively, data suggests that AuNC sensitization is not by classical FRET or NSET and we provide a simplified distance-independent ET model to fit such experimental data.

Dose mapping of porcine coronary arteries using an optical fiber dosimeter.

BACKGROUND: This study is about the measurement of radiation dose contribution to the coronary arteries during intravascular brachytherapy with beta and gamma emitters utilizing in vivo optical fiber dosimeters. METHODS AND MATERIALS: Domestic pigs were used. With each measurement, catheters were introduced into two different coronary arteries, including the left circumflex (LCX), the left anterior descending (LAD), the first diagonal, and/or the right coronary artery (RCA). A radioactive source (192Ir, 90Sr/Y, or 32P) and the dosimeter were loaded in each of these catheters. Data were collected as the dosimeter was being retracted at a constant rate via computer control. RESULTS: The radiation dose was normalized to 100% at a 2-mm radial distance from the source. When radiating a branching artery, the dose to the bifurcation at 5 mm from the source was 35%, 10%, and 3% for the 192Ir (10 seeds), 90Sr/Y (40 mm), and 32P sources, respectively. When utilizing a 23-seed 192Ir source, the dose is 40% at a 5-mm distance. However, radiation of the RCA did not result in dosing to the LAD or LCX using any source. CONCLUSIONS: The dose to adjacent artery segments is less with beta than with gamma emitters. Significant dose exposition is noted when using gamma emitters at a distance of 5 mm. The results can serve as a guideline for establishing prescription doses and safety margins for the treatment of bifurcation lesions and retreatment of the arteries.