Assessing the feasibility of intranasal radiotracer administration for in brain PET imaging

Singh, Nisha; Veronese, Mattia; O’Doherty, Jim; Sementa, Teresa; Bongarzone, Salvatore; Cash, Diana; Simmons, Camilla; Arcolin, Marco; Marsden, Paul; Gee, Antony D.; Turkheimer, Federico

doi:10.1016/j.nucmedbio.2018.08.005

Cited by 7 publications

(7 citation statements)

References 34 publications

(42 reference statements)

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“…11,12 Liquid solutions are noted as a major limitation due to these deposits, and an important point for an increase in local absorbed dose, as noted by our own previous work. 14 Although skin dose is difficult to measure directly, estimations can be easily determined. The conversion factors used here in the analytical method have been designed with external contamination in mind, and the dose is normally calculated to the basal layer of the skin, that is, 70 µm in depth (Hp(0.07), measured in mSv).…”

Section: Discussionmentioning

confidence: 99%

“…We aimed to compare our MC simulations of planar geometry with easier to use user end codes, namely VARSKIN software (based on the results of MC simulations), and also with an analytical equation. All models of the contamination scenario employed an exposure time of 1 h, which is approximately the amount of time required for radiotracer administration and dynamic PET scanning according to our previous preclinical imaging study protocol performing IN administrations of [ 18 F]‐Fallypride and [ 18 F]‐FDG in rats 14 . Our assumption is that after 1 h of imaging, any remaining radiotracer in the nasal cavity can be removed by nasal lavage or irrigation.…”

Section: Methodsmentioning

confidence: 99%

“…All models of the contamination scenario employed an exposure time of 1 h, which is approximately the amount of time required for radiotracer administration and dynamic PET scanning according to our previous preclinical imaging study protocol performing IN administrations of [ 18 F]-Fallypride and [ 18 F]-FDG in rats. 14 Our assumption is that after 1 h of imaging, any remaining radiotracer in the nasal cavity can be removed by nasal lavage or irrigation. Calculations of absorbed dose to the nasal cavity using three different techniques (one MC simulation, one software calculation technique, and one analytical technique) were performed assuming an idealized planar source area of 80 cm 2 representing the radiopharmaceutical covering the entire nasal cavity with no shielding between the source (1 MBq of radiotracer) and the skin surface.…”

Section: B Skin Absorbed Dose Calculationsmentioning

confidence: 99%

“…Recent work has also performed biodistribution studies comparing the IV and IN routes of administration of 52 Mn noting good uptake of the radiotracer in the brain, thyroid, and pancreas 13 . Our own group’s previous work to investigate the IN pathway has performed IV and IN administrations of 18 F‐FDG and 18 F‐fallypride in Sprague–Dawley rats, and summarized that although the route is an attractive option for permeation of the brain for certain radiotracers, the IN technique may not be suitable for these particular molecules 14 …”

Section: Introductionmentioning

confidence: 99%

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Estimation of absorbed radiation doses to skin and S‐values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations

et al. 2021

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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). However, to be viable in a patient population, good image quality as well as safety of the administration should be demonstrated. This work provides radiation dosimetry calculations and simulations related to the radiation safety of performing such experiments in a human cohort. Methods: We performed Monte Carlo (MC) simulations to estimate radiation dose to the skin inside a cylindrical model of the nasal cavity assuming a homogenous distribution layer of 11 C and 18 F and calculated a geometry conversion factor (F P-C) which can be used to convert from a planar geometry to a cylindrical geometry using more widely available software tools. We compared radiation doses from our simulated cylindrical geometry with the planar dose estimates employing our geometry conversion factor from VARSKIN 6.1 software and also from an analytical equation. Furthermore, in order to estimate radiation dosimetry to surrounding organs of interest, we performed a voxelized MC simulation of a fixed radioactivity inside the nasal cavity and calculated S-values to organs such as the eyes, thyroid, and brain. Results: MC simulations of contamination scenarios using planar absorbed doses of 15.50 and 8.60 mGy/MBq for 18 F and 11 C, respectively, and 35.70 and 19.80 mGy/MBq per hour for cylindrical geometries, leading to determination of an F P-C of 2.3. Planar absorbed doses (also in units of mGy/MBq) determined by the analytical equation were 16.96 and 8.68 (18 F and 11 C) and using VAR-SKIN were 16.60 and 9.26 (18 F and 11 C), respectively. Application of F P-C to these results demonstrates values with a maximum difference of 9.41% from the cylindrical geometry MC calculation, demonstrating that when accounting for geometry, more simplistic techniques can be utilized to estimate IN dosimetry. Voxelized MC simulations of radiation dosimetry from a fixed source of 1 MBq of activity confined to the nasal cavity resulted in S-values to the thyroid, eyes, and brain of 1.72 x 10 −6 , 1.93 x 10 −5 , and 3.51 x 10 −6 mGy/MBqÁs, respectively, for 18 F and 1.80 × 10 −6 , 1.95 × 10 −5 , and 3.54 × 10 −6 mGy/MBqÁs for 11 C. Conclusion: Dosimetry concerns about IN administrations of PET radiotracers should be considered before clinical use. Values presented in the simulations such as the S-values can be further used for assessment of absorbed doses in cases of IN administration, and can be used to develop and adapt specific study protocols. All three presented methods provided similar results when considering the use of a geometry conversion factor for planar to cylindrical geometry, demonstrating that standard tools rather than dedicate MC simulations may be used to perform dose calculations in nasal administrations.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: B Skin Absorbed Dose Calculationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estimation of absorbed radiation doses to skin and S‐values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations

et al. 2021

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“…Previous work has used positron emission tomography (PET) imaging in consort with [ 11 C]MX to bind and quantify AP sites [15]. However, the clinical usage of PET for long term and repeated monitoring may be limited by cost, resource availability, and the limits of anatomical specificity [16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair

Srinivasan

Rajagopal

Condie

et al. 2019

IJMS

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Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

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Diagnostic and theranostic intranasal nanointerventions for brain diseases

Upadhaya

Pulakkat

Patravale

2021

Direct Nose-to-Brain Drug Delivery

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Assessing the feasibility of intranasal radiotracer administration for in brain PET imaging

Abstract: Therefore, although an attractive route for brain permeation, we conclude that the intranasal route would present difficulties due to non-specific signal and radiation dosimetry considerations for brain PET imaging.

Cited by 7 publications

References 34 publications

Estimation of absorbed radiation doses to skin and S‐values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations

Estimation of absorbed radiation doses to skin and S‐values for organs at risk due to nasal administration of PET agents using Monte Carlo simulations

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair

Diagnostic and theranostic intranasal nanointerventions for brain diseases

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