Sven-Erik Strand

A Monte Carlo program for the simulation of scintillation camera characteristics

There is a need for mathematical modelling for the evaluation of important parameters for photon imaging systems. A Monte Carlo program which simulates medical imaging nuclear detectors has been developed. Different materials can be chosen for the detector, a cover and a phantom. Cylindrical, spherical, rectangular and more complex phantom and source shapes can be simulated. Photoelectric, incoherent, coherent interactions and pair production are simulated. Different detector parameters, e.g. the energy pulse-height distribution and pulse pile-up due to finite decay time of the scintillation light emission, can be calculated. An energy resolution of the system is simulated by convolving the energy imparted with an energy-dependent Gaussian function. An image matrix of the centroid of the events in the detector can be simulated. Simulation of different collimators permits studies of spatial resolution and sensitivity. Comparisons of our results with experimental data and other published results have shown good agreement. The usefulness of the Monte Carlo code for the accurately simulation of important parameters in scintillation camera systems, stationary as well as SPECT (single-photon emission computed tomography) systems, has been demonstrated.

FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma

Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2‐[18 F] fluoro‐2‐deoxy‐D‐glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC.

Particle sizing and biokinetics of interstitiallymphoscintigraphic agents

The biokinetics of inert lymphoscintigraphic agents strongly depends on their particle size. Different techniques for characterization of colloids are discussed. Experiments have been performed on eight different colloids. The particle size has been investigated with scanning electron microscopy. Activity distributions have been obtained with ultrafiltration and gel-column scanning technique. The colloids suggested for lymphoscintigraphy were found to have a median size of about 40-50 nm except one minimicro-aggregated human serum albumin colloid which has a median particle size around 10 nm. The biokinetics were studied with a scintillation camera in rabbits after a subcutaneous injection. Time-activity curves were generated. After 5 hr the rabbits were dissected and the activity content in different tissues measured. A compartment model for the biokinetics was designed and rate constants evaluated. The total and specific activity uptake in parasternal lymph nodes was highest for the small-particle colloids. The compartment model showed a good fitting to the experimental data.

Lu-177-[DOTA0,Tyr3] Octreotate Therapy in Patients With Disseminated Neuroendocrine Tumors: Analysis of Dosimetry With Impact on Future Therapeutic Strategy

177Lu‐(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan.

Dose-Fractionated Radioimmunotherapy in Non-Hodgkin's Lymphoma Using DOTA-Conjugated, 90Y-Radiolabeled, Humanized Anti-CD22 Monoclonal Antibody, Epratuzumab.

Purpose: Fractionated radioimmunotherapy may improve therapeutic outcome by decreasing heterogeneity of the dose delivered to the tumor and by decreasing hematologic toxicity, thereby allowing an increased amount of radionuclide to be administered. Because humanized anti-CD22 epratuzumab can be given repeatedly, a single-center study was conducted to establish the feasibility, safety, optimal dosing, and preliminary efficacy of weekly administrations of 90Y-labeled 1,4,7,10-tetra-azacyclodecane-N,N′,N″,N‴-tetraacetic acid–conjugated epratuzumab. Experimental Design: Cohorts of three to six patients with B-cell lymphoma received 185 MBq/m2 [90Y]epratuzumab with unconjugated epratuzumab (total protein dose 1.5 mg/kg) once weekly for two to four infusions, with [111In]epratuzumab coadministered at first infusion for scintigraphic imaging and dosimetry. Results: Sixteen patients received treatment without significant infusional reactions. The overall objective response rate was 62% (95% confidence interval, 39-86%) in both indolent (75%) and aggressive disease (50%). Complete responses (CR/CRu) occurred in 25% of patients and were durable (event-free survival, 14-41 months). Two patients receiving four infusions had hematologic dose-limiting toxicity. Serum epratuzumab levels increased with each weekly dose. Of 13 patients with tumor cell CD22 expression determined by flow cytometry, seven of eight with strongly positive results had objective responses, versus one of five with negative or weakly positive results (P = 0.032). Conclusions: Radioimmunotherapy with weekly 185 MBq/m2 [90Y]epratuzumab achieved a high objective response rate (62%) across lymphoma subtypes, including durable CRs. The findings that three weekly infusions (555 MBq/m2, total dose) can be administered safely with only minor toxicity, that antibody levels increased during treatment weeks, and that therapeutic response predominantly occurs in patients with unequivocal CD22 tumor expression provide guidance for future studies.

99mTc-Labeled Superparamagnetic Iron Oxide Nanoparticles for Multimodality SPECT/MRI of Sentinel Lymph Nodes

The purpose of this study was to develop multimodality SPECT/MRI contrast agents for sentinel lymph node (SLN) mapping in vivo. Methods: Nanoparticles with a solid iron oxide core and a polyethylene glycol coating were labeled with 99mTc. The labeling efficiency was determined with instant thin-layer chromatography and magnetic separation. The stability of the radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) was verified in both sterile water and human serum at room temperature 6 and 24 h after labeling. Five Wistar rats were injected subcutaneously in the right hind paw with 99mTc-SPIONs (25–50 MBq, ∼0.2 mg of Fe) and sacrificed 4 h after injection. Two animals were imaged with SPECT/MRI. All 5 rats were dissected; the lymph nodes, liver, kidneys, spleen, and hind paw containing the injection site were removed and weighed; and activity in the samples was measured. The microdistribution within the lymph nodes was studied with digital autoradiography. Results: The efficiency of labeling of the SPIONs was 99% 6 h after labeling in both water and human serum. The labeling yield was 98% in water and 97% in human serum 24 h after labeling. The SLN could be identified in vivo with SPECT/MRI. The accumulation of 99mTc-SPIONs (as the percentage injected dose/g [%ID/g]) in the SLN was 100 %ID/g, whereas in the liver and spleen it was less than 2 %ID/g. Digital autoradiography images revealed a nonhomogeneous distribution of 99mTc-SPIONs within the lymph nodes; nanoparticles were found in the cortical, subcapsular, and medullary sinuses. Conclusion: This study revealed the feasibility of labeling SPIONs with 99mTc. The accumulation of 99mTc-SPIONs in lymph nodes after subcutaneous injection in animals, verified by SPECT/MRI, is encouraging for applications in breast cancer and malignant melanoma.

The Impact of PET and SPECT on Dosimetry for Targeted Radionuclide Therapy

Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for a range of cancers. To date, few treatments have involved the use of dosimetry either to plan treatment or to retrospectively ascertain the absorbed dose delivered during treatment. Also the correlation between absorbed dose and biological effect has been difficult to establish. Tomographic methods permit the determination of the activity volume on a macroscopic scale at different time points. Proper attenuation correction in tomographic imaging requires a patient-specific attenuation map. This can be obtained from scintillation-camera transmission scanning, CT or by using segmented scatter-emission images. Attenuation corrections can be performed either on the projection images, on the reconstructed images, or as part of an iterative reconstruction method. The problem of image quantification for therapy radionuclides, particularly for I-131, is exacerbated by the fact that most cameras are optimised for diagnostic imaging with Tc-99m. In addition, problems may arise when high activities are to be measured due to count losses and mis-positioned events, because of insufficient pile-up and dead time correction methods. Sufficient image quantification, however is only possible if all effects that degrade the quantitative content of the image have been corrected for. Monte Carlo simulations are an appealing tool that can help to model interactions occurring in the patient or in the detector system. This is helpful to develop and test correction techniques, or to help to define detectors better suited to quantitative imaging. PET is probably the most accurate imaging method for the determination of activity concentrations in tissue. PET imaging can be considered for pre-therapeutic treatment planning but ideally requires the use of a radioisotope from the same element as that used for treatment (e.g. I-124 for I-131; Y-86 for Y-90). Problems, however are that--some of the positron emitting isotopes have a shorter half-life--non-standard quantification procedures have to be performed--the availability of the radiopharmaceutical is presently limited; Many 3D-tools and -techniques are now available to the physicist and clinician to enable absorbed dose calculations to both target and critical organs-at-risk. The challenge now facing nuclear medicine is to enable this methodology to be routinely available to the clinic, to ensure common standard operating procedures between centres and in particular to correlate response criteria with absorbed dose estimates.

RADIATION DOSIMETRY IN NUCLEAR MEDICINE

Radionuclides are used in nuclear medicine in a variety of diagnostic and therapeutic procedures. A knowledge of the radiation dose received by different organs in the body is essential to an evaluation of the risks and benefits of any procedure. In this paper, current methods for internal dosimetry are reviewed, as they are applied in nuclear medicine. Particularly, the Medical Internal Radiation Dose (MIRD) system for dosimetry is explained, and many of its published resources discussed. Available models representing individuals of different age and gender, including those representing the pregnant woman are described; current trends in establishing models for individual patients are also evaluated. The proper design of kinetic studies for establishing radiation doses for radiopharmaceuticals is discussed. An overview of how to use information obtained in a dosimetry study, including that of the effective dose equivalent (ICRP 30) and effective dose (ICRP 60), is given. Current trends and issues in internal dosimetry, including the calculation of patient-specific doses and in the use of small scale and microdosimetry techniques, are also reviewed.

Small animal imaging with pinhole single-photon emission computed tomography.

Background. High resolution spatial details of the distribution of activity in three dimensions is required to evaluate the localization and dosimetric properties of radiolabelled monoclonal antibodies in tumors and normal tissues. Planar imaging of small animals with a resolution of 5–10 mm is usually the imaging modality of choice. The authors investigated high resolution singlephoton emission computed tomographic (SPECT) imaging, based on a rotating pinhole scintillation camera. Although the sensitivity of the pinhole collimator is low, several radionuclides offer suitable decay properties to perform pinhole SPECT, especially in conjunction with high activity levels used in radioimmunotherapy.

3D absorbed dose calculations based on SPECT: Evaluation for 111-In/90-Y therapy using Monte Carlo simulations

A general method is presented for patient-specific three-dimensional (3D) absorbed dose calculations based on quantitative SPECT activity measurements. The computational scheme includes a method for registration of the CT study to the SPECT image, and compensation for attenuation, scatter, and collimator-detector response including septal penetration, performed as part of an iterative reconstruction method. From SPECT images, the absorbed dose rate is calculated using an EGS4 Monte Carlo code, which converts the activity distribution to an absorbed dose rate distribution. Evaluation of the accuracy in the activity quantification and the absorbed dose calculation is based on realistic Monte Carlo simulated SPECT data of a voxel-computer phantom and (111)In and (90)Y. Septal penetration was not included in this study. The SPECT-based activity concentrations and absorbed dose distributions are compared to the actual values; the results imply that the corrections for attenuation and scatter yield results of high accuracy. The presented method includes compensation for most parameters deteriorating the quantitative image information. Inaccuracies are, however, introduced by the limited spatial resolution of the SPECT system, which are not fully compensated by the collimator-response correction. The proposed evaluation methodology may be used as a basis for future inter-comparison of different dosimetry calculation schemes.