MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose calculations. Task Group of the MIRD Committee, Society of Nuclear Medicine.

UNLABELLED: The constant-volume urinary bladder model in the standard MIRD Pamphlet No. 5 (Revised) phantom has recognized limitations. Various investigators have developed detailed models incorporating more physiologically realistic features, such as expanding bladder contents and residual volume, and variable urinary input rate, initial volume and first void time. We have reviewed these published models and have developed a new model for calculation of radiation absorbed dose to the urinary bladder wall incorporating these aspects. METHODS: The model consists of a spherical source with variable volume to simulate the bladder contents and a wall represented by a spherical shell of constant volume. The wall thickness varies as the source expands or contracts. The model provides for variable urine entry rate (three different hydration states), initial bladder contents volume, residual volume and first void time. The voiding schedule includes an extended nighttime gap during which the urine entry rate is reduced to one-half the daytime rate. RESULTS: Radiation-absorbed dose estimates have been calculated for the bladder wall surface (including photon and electron components) and at several depths in the wall (electron component) for 2-18F-fluoro-2-deoxy-D-glucose, 99mTc-diethylenetriaminepentaacetic acid (DTPA), 99mTc-HEDP, 99mTc-pertechnetate, 99mTc-red blood cells (RBCs), 99mTc-glucoheptonate, 99mTc-mercaptoacetyltriglicine chelator (MAG3), 99mTc-methylene diphosphonate (MDP), 99mTc-hexamethylpropylene amine oxime (HMPAO), 99mTc-human serum albumin (HSA), 99mTc-MIBI (rest and stress), 123I-/124I-/131I-OIH, 123I/131I-NaI, 125I-iothalamate, 111In-DTPA and 89Sr-SrCl. CONCLUSION: The new model tends to give a higher radiation absorbed dose to the bladder wall surface than the previous models. Large initial bladder volumes and higher rates of urine flow into the bladder result in lower bladder wall dose. The optimal first voiding time is from 40 min to 3 hr postadministration, depending on radiopharmaceutical. The data as presented in tabular and graphic form for each compound provide guidance for establishing radiation absorbed dose reduction protocols.

Intravascular irradiation using Re-186 liquid-filled balloon catheters: correlation between experimental and theoretical studies.

PURPOSE: Optimization of intravascular radiation to reduce stenosis following coronary angioplasty requires the ability to predict the patterns of radiation dose distribution. This investigation evaluated the agreement between Monte Carlo simulations and experimental radiation dose measurements for a radioisotope liquid-filled balloon catheter in a tissue equivalent phantom. METHODS AND MATERIALS: Direct measurements of the radiation dose from Re-186 liquid-filled balloons were made using thermoluminescent dosimeters (TLDs) and radiochromic film. Monte Carlo simulations were carried out using the Monte Carlo N-Particle code system (MCNP4B). RESULTS: The Monte Carlo generated dose values agreed with the experimentally determined results within the statistical uncertainty. A slightly higher penetration was indicated by regression analysis for the TLD data relative to the MCNP4B prediction that may be due to experimental configuration anomalies. For this balloon catheter, approximately 55 mCi of Re-186 will deliver 15 Gy at a 0.5 mm depth in tissue equivalent material in 5 min. CONCLUSIONS: Correlation between experimentally measured dose values and Monte Carlo computation supports the position that MCNP4B simulations constitute a valuable tool for investigating various clinical therapy designs. The agreement between Monte Carlo calculations and experiments provide confidence in applying MCNP4B to more sophisticated geometries of interest, and other methods of intravascular radiation dose delivery.

Rhenium-188(Sn)HEDP for treatment of osseous metastases.

UNLABELLED: Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. METHODS: It was evaluated by in vitro and in vivo testing in the laboratory, in animals and in humans using 188Re from a variety of sources. It may be produced by a desk-top method developed previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of either enriched 187Re or naturally occurring rhenium targets or the use of a 188W/188Re generator. RESULTS: So long as the mass of rhenium in the 188Re-perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg, satisfactory radiochemical yields and purity may be obtained by all methods. The 188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that are similar to those noted previously for 186Re(Sn)HEDP and appears to result in similar benefits and toxicities in patients with skeletal metastases. External radiation exposure monitoring indicates that, only 4 hr after a therapeutic administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1 meter from the patient would be only 0.5 mR/hr. CONCLUSION: Same-day, on-demand, outpatient therapy of disseminated skeletal metastases appears to be feasible with 188Re(Sn)HEDP.

Dosimetric considerations in the radioiodine treatment of macrometastases and micrometastases from differentiated thyroid cancer.

When macrometastases are delineated clearly using current radiographic techniques and/or physical examination and can be shown to concentrate 131I, the therapeutic activity to be administered may be determined quantitatively. Administrations of 131I that will deliver 30,000 rad to residual thyroid tissue or 10,000 +/- 2,000 rad to lymph node metastases will ablate them successfully 80% of the time, and bone marrow depression that is severe enough to require specialized treatment will be avoided if the whole blood dose from a single administration does not exceed 200 rad. When micrometastases are detected only by diagnostic radioiodine imaging and/or elevations of serum thyroglobulin levels, and when a clinical decision is made to treat them with radioiodine, then 131I may not be the isotope choice. With small lesions < 0.05 mm in diameter, the lower energy emissions of 125I therapy may be more suitable. With the advent of alternative methods of patient preparation for radioiodine therapy, empiric approaches that were derived from experience with endogenously hypothyroid patients will require full re-evaluation. Approaches based on quantitative radiodosimetric calculations will continue to be valid because they already consider individual differences in radioiodine kinetics.

Application of a 3D volume 19F MR imaging protocol for mapping oxygen tension (pO2) in perfluorocarbons at low field.

A limited flip angle gradient-echo 3D volume acquisition imaging protocol for mapping partial pressure of oxygen (pO2) in perfluorocarbon compounds (PFCs) at low field (0.14 T) is presented. The PO2 measurement method is based on the paramagnetic effect of dissolved molecular oxygen (O2) which reduces the PFC 19F T1. Specific objectives related to imaging of PFCs through use of the protocol include improved image signal-to-noise characteristics and elimination of 19F chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm is used for suppression of 19F chemical shift artifacts. Application of the protocol is illustrated in a series of calculated PO2 maps of a gas equilibrated, multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of the protocol is demonstrated in vivo through images of a commercially available perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in the liver and spleen of a rat.

In vivo PO2 imaging in the porcine model with perfluorocarbon F-19 NMR at low field.

Quantitative pO2 imaging in vivo has been evaluated utilizing F-19 NMR in the porcine model at 0.14 T for the lungs, liver, and spleen following i.p. administration of the commercial perfluorotributylamine (FC-43)-based perfluorocarbon (PFC) emulsion, Oxypherol-ET. Calculated T1 maps obtained from a two spin-echo saturation recovery/inversion recovery (SR/IR) pulse protocol are converted into quantitative pO2 images through a temperature-dependent calibration curve relating longitudinal relaxation rate (1/T1) to pO2. The uncertainty in pO2 for a T1 measurement error of +/- 5% as encountered in establishing the calibration curves ranges from +/- 10 torr (+/- 40%) at 25 torr to +/- 16 torr (+/- 11%) at 150 torr for FC-43 (37 degrees C). However, additional uncertainties in T1 dependent upon the signal-to-noise ratio may be introduced through the SR/IR calculated T1 pulse protocol, which might severely degrade the pO2 accuracy. Correlation of the organ image calculated pO2 with directly measured pO2 in airway or blood pools in six pigs indicate that the PFC resident in lung is in near equilibrium with arterialized blood and not with airway pO2, suggesting a location distal to the alveolar epithelium. For the liver, the strongest correlation implying equilibrium was evident for venous blood (hepatic vein). For the spleen, arterial blood pO2 (aorta) was an unreliable predictor of pO2 for PFC resident in splenic tissue. The results have demonstrated the utility and defined the limiting aspects quantitative pO2 imaging in vivo using F-19 MRI of sequestered PFC materials.

A Monte Carlo simulation model for radiation dose to metastatic skeletal tumor from rhenium-186(Sn)-HEDP.

UNLABELLED: A Monte Carlo model has been developed for simulation of dose delivery to skeletal metastases by the bone surface-seeking radiopharmaceutical 186Re (Sn)-HEDP. METHODS: The model simulates: (1) the heterogeneous small scale geometry of the soft tissue/bone-spicule structure in the lesions as determined by histomorphometric measurements of histologic specimens, (2) the small scale spatial distribution of the radiopharmaceutical on the lesion bone spicule surface as determined by autoradiography, and (3) the 186Re beta and conversion electron decay spectrum and the associated charged particle transport within the modeled geometries. The results are compared with the commonly employed uniform lesion model, which assumes: (1) homogeneous lesion morphology, (2) uniform distribution of radioactivity within the lesion, and (3) complete energy deposition by charged particles within the lesion due to decay of this activity. Gamma and x-ray photons from the 186Re spectrum were assumed to escape from the lesion volume in both models. RESULTS: Results show a significant dependence on the bone volume fraction and hence on the histology of the lesion (lytic, blastic or mixed). The uniform lesion model calculations underestimate the radiation dose to blastic lesions by as much as a factor of 1.8. However, for lytic lesions with low bone volume fractions, both models provide similar dose values. CONCLUSIONS: These new model calculations provide a mechanism for optimizing treatment planning and dose response evaluations of therapeutic bone-seeking radiopharmaceuticals.

Evaluation of the influence of the aqueous phase bioconstituent environment on the F-19 T1 of perfluorocarbon blood substitute emulsions.

Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local PO2 and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant PO2, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.

Implementation of a modified birdcage resonator for 19F/1H MRI at low fields (0.14 T).

Fluorine-19 nuclear magnetic resonance of perfluorinated blood substitute materials provides a method for determination of oxygen tension (pO2) in vivo. Use of a double resonant 19F/1H radio frequency coil allows convenient correlation between the high resolution anatomic presentation of proton images and the fluorine distribution. However, quantitative 19F measurements require an RF coil with good H1 field homogeneity over the image volume and a high quality factor (Q) to minimize errors caused by the low signal-to-noise levels available in in vivo imaging and image nonuniformities introduced by the large chemical shift of fluorocarbons. The birdcage coil design provides a high Q structure with optimum H1 field uniformity and fill factor. However, at low resonance frequencies, the inherently low inductance of the birdcage geometry requires the use of a large number of chip capacitors giving rise to unwieldy coil fabrication and increased cost. This communication describes a modification to the birdcage design that reduces the chip capacitor requirement by at least a factor of 4 for a given dimension, yet retains the essential characteristics of the birdcage design. The modified structure was tuned for double resonance at 5.7/6.0 MHz for 19F/1H magnetic resonance imaging at 0.14 T. For a coil with a length to diameter ratio of 1.67, an H1 uniformity of +/- 2% for the 19F resonance was obtained over a cylindrical region with radius approximately 0.6r (r = radius of coil) and length approximately 1.8r within the coil.

Quantitative pO2 imaging in vivo with perfluorocarbon F-19 NMR: tracking oxygen from the airway through the blood to organ tissues.

The physiological redistribution of perfluorocarbon (PFC) compounds to liver, spleen, bone marrow, and lung after intravenous (i.v.) or intraperitoneal (IP) administration of PFC emulsions affords the unique opportunity for non-invasive monitoring of oxygenation status of these organs and tissues utilizing fluorine (F-19) nuclear magnetic resonance (NMR) imaging techniques. PFCs also may be introduced directly into the pulmonary airways by procedures such as liquid ventilation, intratracheal instillation, or aerosol inhalation. Considerations of importance when establishing methodology for accurate quantitation of oxygen partial pressure (pO2) in vivo using F-19 NMR include: 1.) error analysis of the calibration curves which relate pO2 to the measured PFC F-19 relaxation rate, 2.) optimization of the NMR pulse sequence for efficient oxygen sensitive data acquisition and, 3.) fluorine signal independence from emulsion aqueous phase bioconstituents. The porcine model was investigated at 0.14T following i.v. or IP administration of the PFC emulsion containing perfluorotributylamine (FC-43) to demonstrate the capability for tracking oxygen with F-19 NMR from the lung through the blood to selected organ tissues. Quantitative pO2 projection images and isobaric contour graphs were derived for the liver, spleen, and lungs as a function of inspired oxygen. Blood pO2 levels in aorta, pulmonary artery, and hepatic vein were monitored simultaneously with NMR imaging for correlative analysis.

Predictive estimate of blood dose from external counting data preceding radioiodine therapy for thyroid cancer.

Bone marrow depression following 131I therapy for metastatic thyroid cancer can occur in up to one-quarter of all patients so treated. An analysis was made of the 131I whole body (WB) retention and its relationship to activity in blood for 46 patients (45 adult, 1 adolescent in 49 total studies) to define the accuracy of utilizing WB external counting data as a predictor of blood dose in comparison to the more classical method which requires data from sequential blood samples. The mean percentage differences between blood dose estimates based on external WB counting and those calculated by the classical method lie within +/- 10%. The WB methodology provides a useful first-order approximation for hematopoietic dose estimates in adult patients undergoing 131I therapy for thyroid cancer.

MIRD Pamphlet No. 14: a dynamic urinary bladder model for radiation dose calculations.

The constant-volume urinary bladder model in the standard MIRD phantom has recognized limitations. Various investigators have developed detailed models incorporating more physiologically realistic features such as expanding bladder contents and residual volume, and variable urinary input rate, initial volume and first void time. We have reviewed these published models and have developed a new model incorporating these factors. The model consists of a spherical source with variable volume to simulate the bladder contents and a wall represented by a spherical shell of constant volume. The wall thickness varies as the source expands or contracts. The model provides for variable urine entry rate (three different hydration states), initial bladder contents volume, residual volume and first void time. The voiding schedule includes an extended nighttime gap during which the urine entry rate is reduced to one-half the daytime rate. Radiation dose estimates have been calculated for the bladder wall surface (including photon and electron components) and at several depths in the wall (electron component) for [18F]FDG, 99mTc-DTPA, 99mTc-HEDP, [99mTc]pertechnetate 99mTc-RBCs, 99mTc-glucoheptonate, 99mTc-MAG3, [123I]/[124I]/[131I]OIH and sodium [131I]iodide(Nal). The initial bladder volume and first void time that provide the lowest radiation dose to the bladder wall are determined separately for each compound to give guidance for establishing dose reduction protocols.

Quantitation of perfluorocarbon blood substitutes in tissues using F-19 magnetic resonance spectroscopy.

F-19 Magnetic Resonance Spectroscopy (MRS) has been used to quantitate the biodistribution of perfluorocarbon (PFC) blood substitutes in porcine tissues following intraperitoneal administration of a 20% w/v perfluorotributylamine (FC-43) based emulsion. PFC tissue concentrations were determined for spleen, liver and lung tissues from juvenile pigs ranging in weight from 12 to 15 kg. Typical average values (mmoles FC-43/gram tissue) ranged from 0.23-0.39 for spleen; 0.09-0.13 for liver; and 0.09-0.12 for lung. A description of this spectroscopy based quantitation technique will be presented. F-19 MRS is a specific, rapid, and accurate method for measurement of PFC tissue concentrations.

Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases.

Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo.

Rhenium-186 (tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that simultaneously localizes in multiple skeletal metastases in patients with advanced cancer. A single intravenous administration of 30-35 mCi (1110-1295 MBq) is associated with a prompt, significant relief of osseous pain in about 80% of such patients. The efficacy of this new compound was evaluated further by utilizing a double-blind crossover comparison with 99mTc-methylene diphosphonate (MDP) as a radioactive placebo. The new rhenium compound resulted in a significantly (p less than 0.05) greater decrease in pain than did treatment with the radioactive placebo. Rhenium-186(Sn)HEDP appears to be a useful new compound for the palliation of painful skeletal metastases.

Magnetic resonance imaging of rat brain following in vivo disruption of the cerebral vasculature.

Intravenous administration of hyperosmotic mannitol into rats produced a disruption of the blood-brain barrier (BBB). This was visualized by T1 weighted magnetic resonance (MR) imaging following intravenous administration of the MR contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Following administration of the Gd-DTPA there was an increase in signal intensity corresponding to the cerebral cortex. There was also an increase in signal intensity in features corresponding to the lateral ventricles. However, there was no increase in signal intensity within the striatum indicating that the vasculature within the striatum was resistant to disruption by the hyperosmotic mannitol. The tumors formed by C-6 glioma cells were isointense with rat brain on precontrast MR images. Following intravenous administration of Gd-DTPA, in a representative rat, the tumor was visualized as areas of high signal intensity. There was no enhancement of normal brain by Gd-DTPA. Thus, the tumor had different vascular properties than the host brain with respect to permeability of the contrast agent. Furthermore, Gd-DTPA did not enter the normal brain via the tumor. Thirty days following unilateral injection of kainic acid (KA: 5 nmol) into rat striatum, the shrinkage of the lesioned striatum and the concomitant enlargement of the lateral ventricles was visible on the precontrast MR images. Following administration of Gd-DTPA, there was no enhancement of any regions of the brain. Therefore, the structural perturbations of the striatum produced by KA lesions were not accompanied by disruption of the BBB. These studies demonstrate that MR imaging represents a useful technique for investigating in vivo the perturbation of the cerebral vasculature in rat models of neuropathologies.

The modification of specific absorption rates in interstitial microwave hyperthermia via tissue-equivalent material bolus.

Patterns of specific absorption rates generated by interstitial, microwave antenna arrays must be experimentally ascertained and quantified to facilitate their clinical incorporation. Phantom studies involved the use of four single-gap, coaxial antennas oriented in a 2 cm square array. These dipoles were driven in phase by a microwave generator at a frequency of 915 MHz. The inherent limitations in modifying the specific absorption rate patterns were addressed with the addition of bolus to the phantom. These additions of Guy's muscle tissue-equivalent material were made either proximal or distal to the phantom proper. Experiments conducted in the presence and absence of tissue-equivalent material bolus showed the ability to achieve broader bands of 50% power deposition in certain bolus conditions. These heating patterns were sufficiently reproducible and predictable to warrant clinical application of the bolus addition. A through-and-through method of catheter implantation allowed for bolus addition when deemed necessary. Treatments with veterinary and human patients using the bolus method to modify heating patterns yielded augmented patterns of power deposition. The effective length of the antennas that would radiate efficiently was essentially broadened via introduction of a microwave-interacting medium. As a result of the tissue equivalent material's ability to absorb microwave power, it was necessary to interpose minimally-interactive styrofoam spacers to limit heat transfer effects at the tissue-bolus interfaces.

T1 and T2 weighted magnetic resonance imaging of excitotoxin lesions and neural transplants in rat brain in vivo.

On T1- and T2-weighted magnetic resonance (MR) images obtained at 0.14 T the rat brain was visible in the rat head as an area of relative high signal intensity. The enlarged lateral ventricles produced by intrastriatal injections of the excitotoxin kainic acid (KA) were clearly visible as areas of low signal intensity in T1-weighted images but could not be differentiated from normal brain tissue on T2-weighted images for the protocols utilized. Repeated T1-weighted MR images of individual rats demonstrated a progression in the extent of the lesions over an approximately 14-week period following the injection of KA. On the T2-weighted images, areas of relatively high signal intensity corresponding to tissue on the lesioned side of the brain were evident. As the lesion progressed and the remaining tissue visible on the T1-weighted images decreased, the region of high signal intensity visible on the T2-weighted images diminished. This area of high signal intensity on the T2-weighted images appeared to correspond to tissue undergoing a neurodegenerative process. MR images from contiguous slices of brain demonstrated the extent of the KA-induced degeneration throughout the brain, although volume averaging of multiple brain structures was a possible confounding factor. Features apparently corresponding to fetal striatal tissue transplants growing within the enlarged lateral ventricle were visible on T1-weighted images but could not be discriminated on the T2-weighted images. MR imaging is useful for monitoring in vivo the anatomical location and progression of excitotoxin lesions and the location of fetal striatal tissue transplants in lesioned rat brain.

Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer.

Rhenium-186(tin) hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in areas of osseous metastases in a manner similar to that of standard bone-scanning agents. It also emits beta particles with sufficient energy to be therapeutically useful. A single intravenous injection of about 33 mCi (1,221 MBq) was given to each of 20 elderly patients with advanced skeletal metastases from hormonally resistant prostate cancer. Prompt, significant relief of pain occurred 80% of the time with no significant side effects and only minimal, transient marrow toxicity. Re-186(Sn) HEDP appears to be a useful new agent for the palliation of painful osseous metastases in prostate cancer.

A magnetic resonance imaging contrast agent differentiates between the vascular properties of fetal striatal tissue transplants and gliomas in rat brain in vivo.

The tumors formed by rat C-6 glioma cells were isointense with the normal rat brain on precontrast T1 weighted magnetic resonance (MR) images. Following i.v. peripheral administration of the MR imaging contrast agent gadolinium (Gd)-DTPA, there was no significant change in the signal intensity from normal brain tissue. However, the tumor appeared as areas of high signal intensity demonstrating the abnormal vascular properties of the tumor. Fetal rat striatal tissue transplanted into unlesioned adult rat striatum appeared isointense with the host brain on precontrast T1 weighted images and there was no evidence for enhancement of the transplanted tissue relative to host brain following i.v. administration of Gd-DTPA. Using this technique we found no evidence with respect to permeability of the contrast agent of an abnormal blood-brain barrier within the striatal transplant in vivo.