11:52 CET
306 - Do.MoRe - Parallel Session: Diagnostic Dosimetry
Radionuclide Therapy & Dosimetry
Sunday, October 13, 11:30 - 12:45
Type of session: Do.MoRe Track
Topic: Radionuclide Therapy & Dosimetry
Sub topic: 808 Preclinical and Clinical Dosimetry & Radiobiology
Chairperson: M. Abuqbeitah (Istanbul/TR)

Radiation Dosimetry of 18F - AzaFol as the the first Folate Receptor-alpha (FRα) directed PET-Tracer
S. Gnesin1, J. Mueller2, I. Burger3, A. Meisel4, M. Choschzick5, C. Mueller6, R. Schibli7, S. M. Amethamey7, J. O. Prior8, N. Schaefer8;
1Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, Lausanne, SWITZERLAND, 2Department of Radiology and Nuclear Medicine, Cantonal Hospital St Gallen, St. Gallen, SWITZERLAND, 3Department of Nuclear Medicine, Kantonsspital Baden, Baden, SWITZERLAND, 4Department of Internal Medicine - Hematology & Oncology, Stadtspital Waid, Zurich, SWITZERLAND, 5Institute for Pathology and Molecular Pathology, University Hospital of Zurich, Zurich, SWITZERLAND, 6Center for Radiopharmaceutical Sciences ETH-PSI, Paul Scherrer Institute, Villigen-PSI, Villigen, SWITZERLAND, 7Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, SWITZERLAND, 8Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Lausanne, SWITZERLAND.

Aim/Introduction: The FRα has evolved to a valuable diagnostic and therapeutic target in different cancer entities. Here we present the first in-human radiation dosimetry results of a prospective, multicentric trial (NCT03242993) evaluating the 18F-AzaFol as the first clinically-assessed PET-tracer targeting the FRα. Materials and Methods: The prospective, multi-centric study was conducted in three Swiss academic hospitals. Eligible patients (n=6) presented a histologically confirmed ovarian cancer or adenocarcinoma of the lung with measurable lesions in the standard of care imaging modality with an indication for systemic treatment. All patients had TOF-PET acquisitions at 5, 10, 15, 30, 40, 50 and 60 minutes after the intravenous injection of 327 MBq (SD=37, range: 299-399 MBq) of 18F-AzaFol. Source organ segmentation for brain, thyroid, lungs, heart, liver, spleen, stomach, kidneys, prostate (in men), red marrow, intestines, whole body, for the choroid plexuses and for tumors (primary carcinoma and metastases) was performed using the PMOD software based on sequential PET/CT data. Time integrated activity coefficients (TIAC) were calculated by bi-exponential analytical integration of the time activity curves for 0 ≤ t ≤ 60min then assuming mono-exponential physical decay to infinite. Organ absorbed doses (AD) and patient effective doses (ED) where assessed using the OLINDA/EXM v.2.0 software using a urinary voiding period of 1h. The OLINDA/EXM sphere model was used to obtain AD in tumors. Dose estimates in patients were compared with those extrapolated from a previous study in mice [1]. Results: No patient had any serious adverse event related to the experimental substance. The organs receiving the highest AD were the urinary bladder wall, the liver, the kidneys and the small intestine (51.3, 50.6, 44.9 and 26.2 μGy/MBq respectively). Considering a 1h urinary voiding time, the ED across our patient cohort and for the gender-averaged reference person were of 18.3±2.7 and 20±1.4 μSv/MBq respectively. ED in human exceeded the value of 13.2 μSv/MBq obtained from pre-clinical data. A specific biologic uptake and a significant AD (30 μGy/MBq) were reported for the choroid plexuses. Average AD in tumors was 26.4 μGy/MBq (range: 9.6-47.1 μGy/MBq). Conclusion: 18F-Azafol is a PET agent with favourable dosimetric properties and reasonable radiation dose burden in patients (comparable to 18F-FDG), which merits further evaluation to assess its performance in patients with ovarian and lung adenocarcinoma. References: [1] T. Betzel et al, Chem. 2013 Feb 20;24(2):205-14.

Biodistribution and radiation dosimetry study of 68Ga-FAPi-46 PET imaging in patients with various cancers
C. Meyer1,2, M. Dahlbom1,2, J. Czernin2, S. Vauclin3, T. Lindner4, U. Haberkorn4, J. Calais2;
1Physics & Biology in Medicine Interdepartmental Graduate Program, UCLA, Los Angeles, CA, UNITED STATES OF AMERICA, 2Department of Molecular & Medical Pharmacology, UCLA, Los Angeles, CA, UNITED STATES OF AMERICA, 3DOSIsoft SA, Cachan, FRANCE, 4Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, GERMANY.

Aim/Introduction: Targeting cancer-associated fibroblasts (CAFs) has become an attractive goal in research and industry given that CAFs can constitute as much as 90% of tumor stroma. The serine protease, fibroblast activation protein (FAP), is highly overexpressed in CAFs, suggesting FAP as a promising stromal target(1). The recently developed quinolone-based FAP-inhibitor PET tracer, 68Ga-FAPI-46, has demonstrated encouraging results with high tumor-to-background ratios (TBR) in patients with various cancers(2). Here we present a biodistribution and radiation dosimetry study of 68Ga-FAPi-46 PET imaging in cancer patients. Materials and Methods: Radiotracer synthesis and image acquisition were conducted at the University of Heidelberg; image analysis and dosimetry were performed at UCLA. Six patients with different cancers underwent serial PET/CT 68Ga-FAPi-46 scans at three time points following radiotracer injection: 10 minutes, 1.2 hours, and 3.3 hours (injected activity range 214-246 MBq). Source organ contouring and activity accumulation was calculated using PLANET®Dose (DOSIsoft SA, Cachan, France). The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, and uterus. OLINDA/EXM was used to fit the organ activity kinetic data with a monoexponential decay function and integrated according to MIRD formalism to yield total body and organ absorbed doses. Standardized uptake values (SUV) and TBR were generated from the contoured tumor and source organ volumes. Spherical volumes in muscle and blood pool were also obtained for TBR. Results: At all timepoints, the highest organ SUV was observed in the kidneys. Tumor and organs SUVs decreased with time whereas TBRs increased with time. The highest TBRs at 3.3 hours were observed with the marrow (32.2), muscle (23.1), spleen (19.6), and liver (17.3). The organs with the highest absorbed doses are the kidneys (1.66E-02 mGy/MBq), followed by the heart wall (1.11E-02 mGy/MBq) and liver (1.01E-02 mGy/MBq). The average total body effective dose is 7.84E-03 mSv/MBq - similar to reported values for related FAP-inhibitors(3). Thus for administration of 200 MBq 68Ga-FAPi-46 the total body effective dose is 1.57 mSv ± 0.26 mSv, in addition to approximately 3.7 mSv from one low-dose CT attenuation scan. Conclusion: 68Ga-FAPi-46 PET/CT imaging is safe: for administration of 200 MBq(5.4 mCi) of 68Ga-FAPi-46 the whole body effective dose including CT is 5.3 mSv. The biodistribution study showed high TBRs increasing over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications. References: 1Hamson et al.(2014) Proteomics Clin. Appl., 8(5-6):454-463. 2Kratochwil et al.(2019) JNM, Epub ahead of print.3Giesel et al.(2018) JNM, 60(3):386-392.

Patient-Specific Estimates of Organ Dose in Paediatric 18FDG PET/CT Imaging Studies
F. Fahey1,2, C. Kofler3, B. Sexton-Stallone1, R. Reddy1, R. MacDougall1, W. Bolch3;
1Boston Children's Hospital, Boston, MA, UNITED STATES OF AMERICA, 2Harvard Medical School, Boston, MA, UNITED STATES OF AMERICA, 3Crayton Pruitt Family Dept. of Biomedical Engineering, University of Florida, Gainesville, FL, UNITED STATES OF AMERICA.

Aim/Introduction: Hybrid imaging using PET/CT provides crucial clinical information for a variety of paediatric conditions. Fahey et al. [1] noted that currently there are no standard guidelines for the CT portion of a PET/CT in children. At Boston Children’s Hospital (BCH), a diagnostic-quality (Dx) CT is acquired over essential portions of the field-of-view, with low-dose attenuation correction (AC) CT applied to the remainder of the PET field-of-view. The objective of this study was to estimate CT and FDG organ and effective doses in a cohort of BCH patients undergoing FDG PET/CT. Materials and Methods: The UF/NCI phantom library was used to estimate organ dosimetry on 163 PET/CT scans performed on 100 children imaged at BCH (47 females, 53 males; 1 - 19 years, mean 11.4 years). For the PET component, organ dose coefficients from the UF/NCI reference phantom library were interpolated across patient weight to determine patient-specific organ dose coefficients. These coefficients were scaled by FDG administered activity recommendations from the North American Guidelines for children and adolescents [2]. For the CT component, patients were matched by height/weight to individual phantoms within the UF/NCI phantom library. CT parameters as well as scan length and body region imaged were taken into consideration. An attenuation-based algorithm was applied to account for tube current modulation (TCM). Patients in the cohort were scanned with specific BCH AC and Dx protocols. Results: Effective dose of the FDG PET component ranged from 4.1 to 9.2 mSv (average 5.8 mSv). The effective doses of the CT component for AC and Dx scans ranged from 0.01 to 3.04 mSv (average 0.9 mSv) and 0.19 to 11.2 mSv (average 4.1 mSv), respectively. For the combined PET/CT, effective doses for the AC and Dx scans ranged from 4.8 to 9.6 mSv (average 6.9 mSv) and 5.3 to 17.7 mSv (average 10.1 mSv), respectively. The FDG, CT and total PET/CT effective doses all varied with body weight. Conclusion: This work demonstrates the dependence of paediatric PET/CT effective dose (FDG, CT and total) on body weight. The CT effective dose also depends on scan type (AC or Dx) and CT acquisition parameters (kVp, effective mAs, scan length and body region imaged) as well as the use of TCM. This work also highlights the range of effective dose typical in paediatric PET/CT imaging. References: 1. Fahey FH, et al. J Nucl Med. 2017;58:1360-1366. 2. Treves ST, et al. J Nucl Med. 2016;57:15N-18N.

Dosimetric Impact of Modeling the Epiphyseal Plates in Pediatric99mTc-MDP Studies
J. L. B. Brown1, Y. Li2, B. Sexton-Stallone3, X. Cao3, D. Plyku2, E. C. Frey2, S. T. Treves3, F. H. Fahey3, G. Sgouros2, W. E. Bolch1;
1University of Florida, Gainesville, FL, UNITED STATES OF AMERICA, 2Johns Hopkins University, Baltimore, MD, UNITED STATES OF AMERICA, 3Harvard Medical School, Boston, MA, UNITED STATES OF AMERICA.

Aim/Introduction: 99mTc labeled methylene diphosphonate (MDP) is a commonly used radiopharmaceutical for imaging skeletal regions of high bone turnover. These regions include fractures, infections, and tumors. In pediatric patients, 99mTc-MDP will also localize within the epiphyseal plates. Present biokinetic models given by the ICRP do not account for increased uptake. The present study aims to quantify the dosimetric impact of epiphyseal plate uptake through explicit modeling of the epiphyseal plates within the femur of the reference 10-year-old. The simulation study employs polygon mesh models of cortical bone, medullary marrow, distal and proximal trabecular spongiosa, and epiphyseal plates. Polygon mesh Monte Carlo (MC) radiation transport is a recent advancement that supersedes the implementation of memory intensive voxel models.
Materials and Methods: The UF/NCI reference 10-year-old phantom used in the study was modified to include epiphyseal plates in the long bones. To create the epiphyseal plates, a Boolean splitting operation is performed at the location of the epiphyseal plate and two planes that are separated 0.08 mm. This operation results in a 0.08-mm structure representing the epiphyseal plate. Phantom triangle mesh structures are converted to a tetrahedral mesh using Tetgen. MC radiation transport was performed using PHITS to assess doses to all structures in the model.
Results: Results were generated using an isolated femur where the epiphyseal plates of the proximal femoral head, greater trochanter and the distal femoral head were modeled. Cortical bone, spongiosa, and epiphyseal plates were then independently simulated as source regions using the 99mTc decay scheme. This approach allows the assessment of varying levels of activity for each source organ. Results for femur active marrow dose are shown to be highly dependent on the percent of total femur activity localized in the epiphyseal plate. For all structures, increasing the 99mTc-MDP activity concentration within the epiphyseal plates lowers the absorbed dose to active bone marrow in the 10-year femur. Future efforts will extend this modeling approach to all skeletal sites, and for all reference patient ages. Conclusion: This work demonstrates the need for incorporating epiphyseal plates in long bones for pediatric dosimetry. The assumption of a uniform uptake across all bone surfaces leads to an overestimation of active marrow dose in comparison to that assuming some uptake to the growth plates. Future work will incorporate epiphyseal structures in all other regions of the pediatric skeleton.
References: Acknowledgements: Grant R01 EB013558 from the National Institute for Biomedical Engineering and Bioengineering.$$table_{C3853D52-1442-4843-B2D3-0AB86EE3AED2}$$

Radiation dosimetry of nasally administered PET agents using computer simulations
J. O' Doherty1,2, E. Hippelainen3,4, C. Mangini5, D. Hamby6, N. Singh7;
1Sidra Medicine, Doha, QATAR, 2Weill Cornell Medicine Qatar, Doha, QATAR, 3Helsinki University Hospital, Helsinki, FINLAND, 4University of Helsinki, Helsinki, FINLAND, 5Rennaisance Code Development, Corvallis, OR, UNITED STATES OF AMERICA, 6Renaissance Code Development, Corvallis, OR, UNITED STATES OF AMERICA, 7Oxford University, Oxford, UNITED KINGDOM.

Aim/Introduction: The intranasal (IN) administration of radiopharmaceuticals is of interest in being a viable route for the delivery of radiopharmaceuticals that do not ordinarily cross the blood brain barrier (BBB) [1]. For this imaging technique to be viable in a patient population, certain conditions need to be met for clinical use, for example good image quality and safety and efficacy of the administration. This work provides initial dosimetry calculations related to the safety of performing such experiments in patients. Materials and Methods: We utilized an analytical equation and VARSKIN software to estimate the radiation dose to the skin tissue inside the nasal cavity assuming a homogenous distribution of F-18 and C-11 radiotracers. Furthermore, we performed a direct Monte Carlo simulation of radiation transport in tissue, and estimated radiation dosimetry to organs of interest such as the eyes, thyroid and brain by way of calculation of dose factor (DF) values used in dosimetry calculations. Results: Analytical and VARSKIN calculation methods estimated absorbed radiation doses to the skin of the nasal cavity of approximately 11 mGy/MBq and 7 mGy/MBq per hour for 18F and 11C radiotracers administered via IN. Direct Monte Carlo simulations of radiation transport resulted in DF values from nasal cavity to the thyroid, eyes and brain of 1.72x10-6, 1.93x10-6 and 3.51x10-6 mGy/MBq·s respectively for F-18 radiotracers and 1.8x10-6, 1.95x10-5 and 3.54x10-6 mGy/MBq·s for C-11 radiotracers respectively. Conclusion: Dosimetric concerns about IN administrations of PET radiotracers should be considered before human use. Depending on the administered amount of activity via the IN route, values presented in this work can be used for assessment of dosimetric concerns. Based on these calculations, absorbed dose and thus safety of IN administration of future study protocols can be balanced with requirements for good image quality. References: [1] N Singh, M Veronese, J O'Doherty, T Sementa, S Bongarzone, D Cash, C Simmons, M Arcolin, P K Marsden, A Gee, F ETurkheimer. Assessing the feasibility of intranasal radiotracer administration for in brain PET imaging. Nuc Med Biol, 66, 32-39, 2018

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