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Title: Assessments for High Dose Radionuclide Therapy Treatment Planning

Abstract

Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiationmore » Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.« less

Authors:
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
15005506
Report Number(s):
PNNL-SA-37552
600306000; TRN: US0305339
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Radiation Protection Dosimetry, 105(1-4):581-586
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CLINICAL TRIALS; CRITICAL ORGANS; DOSIMETRY; GAMMA CAMERAS; NEOPLASMS; NUCLEAR MEDICINE; PLANNING; RADIATION DOSES; RADIOISOTOPES; THERAPY; US FDA; internal dosimetry; radionuclides; treatment planning; high-dose; cancer treatment

Citation Formats

Fisher, Darrell R. Assessments for High Dose Radionuclide Therapy Treatment Planning. United States: N. p., 2003. Web. doi:10.1093/oxfordjournals.rpd.a006307.
Fisher, Darrell R. Assessments for High Dose Radionuclide Therapy Treatment Planning. United States. doi:10.1093/oxfordjournals.rpd.a006307.
Fisher, Darrell R. 2003. "Assessments for High Dose Radionuclide Therapy Treatment Planning". United States. doi:10.1093/oxfordjournals.rpd.a006307.
@article{osti_15005506,
title = {Assessments for High Dose Radionuclide Therapy Treatment Planning},
author = {Fisher, Darrell R.},
abstractNote = {Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.},
doi = {10.1093/oxfordjournals.rpd.a006307},
journal = {Radiation Protection Dosimetry, 105(1-4):581-586},
number = ,
volume = ,
place = {United States},
year = 2003,
month =
}
  • Before therapy with unsealed radionuclides, a dosimetry assessment must be performed for each patient. We present the interactive software tool ULMDOS, which facilitates dosimetric calculations, enhances traceability, and adequate documentation. ULMDOS is developed in IDL 6.1 (Interactive Data Language) under Windows XP/2000. First the patient data, the radiotracer data, and optionally urine and serum data are entered. After loading planar gamma camera images and drawing regions of interest, the residence times can be calculated using fits of the time activity data to exponential functions. Data can be saved in ASCII format for retrospective examination and further processing. ULMDOS allows onemore » to process the dosimetric calculations within a standardized environment, spares the time-consuming transfer of data between different software tools, enables the documentation of ROI and raw data, and reduces intraindividual variability. ULMDOS satisfies the required conditions for traceability and documentation as a prerequisite to routine use in clinical settings.« less
  • Purpose: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Methods: Planar and SPECT data were available for a patient examined with {sup 111}In-DTPA-octreotide at 0.5 (planar only), 4, 24, andmore » 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., {sup 111}In, {sup 90}Y and {sup 177}Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Results: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for {sup 90}Y and {sup 177}Lu. Nevertheless, for {sup 111}In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated treatment planning are compatible with real activities administered to patients in PRRT. Conclusions: The 3D-RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.« less
  • Purpose: Dosimetry for targeted radionuclide therapy (TRT) is moving away from conventional model-based methods towards patient-specific approaches. To address this need, a Monte Carlo (MC) dosimetry platform was developed to estimate patient-specific therapeutic 3D dose distributions based on pre-treatment imaging. However, because a standard practice for patient-specific internal dosimetry has not yet been established, there are many sources of dosimetric uncertainties. The goal of this work was to quantify the sensitivity of various parameters on MC dose estimations. Methods: The ‘diapeutic’ agent, CLR1404, was used as a proof-of-principle compound in this work. CLR1404 can be radiolabeled with either {sup 124}Imore » for PET imaging or {sup 131}I for radiotherapy or SPECT imaging. PET/CT images of 5 mice were acquired out to 240 hrs post-injection of {sup 124}I-CLR1404. The therapeutic {sup 131}I-CLR1404 absorbed dose (AD) distribution was calculated using a Geant4-based MC dosimetry platform. A series of sensitivity studies were performed. The variables that were investigated included the PET/CT voxel resolution, partial volume corrections (PVC), material segmentation, inter-observer contouring variability, and the pre-treatment image acquisition frequency. Results: Resampling the PET/CT voxel size between 0.2–0.8 mm resulted in up to a 13% variation in the mean AD. Application of the PVC increased the mean AD by 0.5–11.2%. Less than 1% differences in ROI mean AD were observed between the tissue segmentation schemes using 4 and 27 different material compositions. Inter-observer contouring variability led to up to a 20% CoV (stdev/mean) in the mean AD between the users. Varying the number and frequency of pre-treatment images used resulted in changes in mean AD up to 176% compared to the case using all 12 images. Conclusion: Voxel resolution, contour segmentation, the image acquisition protocol most significantly impacted patient-specific TRT dosimetry. Further work is needed to develop a standard protocol that optimizes accuracy and efficiency for patient-specific internal dosimetry. BT and JG are affiliated with Cellectar Biosciences which owns the licensing rights to CLR1404 and related compounds.« less
  • With the new developments of tumor targeting agents (e.g. monoclonal antibodies, peptides etc.) now and better methods to calculate the absorbed dose and dose rate need to be developed. Conjugate view activity quantification in dose planning may be insufficient because of problems with under- and over-lying activity and volume determination. Then, by using the standard MIRD S-values to estimate the absorbed dose to the different organs, another error is included in the calculations. Even if a resealing of the organ masses can be done, the different shapes of the organs, compared with the MIRD phantom, may give large errors. Quantitativemore » SPECT overcomes these problems. Properly attenuation and scatter corrected SPECT slices gives the {open_quotes}true{close_quotes} activity distribution (within the limits of the spatial resolution of the scintillation camera) in the patient. A Monte Carlo code that simulates photon transport within the patient using density maps, has been developed. The advantage is that the body contour and organs as lungs and skeleton can be easily included from a CT study of the patient. If the mean absorbed dose to an organ is wanted, organ volumes can be obtained from the CT study. All electrons are considered locally absorbed at the decay or interaction site. No variance reducing methods have been used. When simulating the MIRD phantom, the user can easily include self defined organs and regions, both as source and target regions. To test the validity of the code, the MIRD phantom has been incorporated and comparison with published specific absorbed fractions and S-values has been done to validate the calculation procedure. Good agreement is shown, S-values for most organs lie within 5-10 % from the MIRD data. Discrepancies, however, of a factor of 2-5 have been found, especially in the lung and the active bone marrow.« less
  • Purpose: The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning. Methods and materials: Patients treated with this regimen initially receive an I-125 implant prescribed tomore » 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters ({alpha}, {beta}, potential doubling time for prostate cancer cells [T{sub pot}], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens. Results: The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning. Conclusions: We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.« less