Radiotheranostics: a roadmap for future development

Herrmann, Ken; Schwaiger, Markus; Lewis, Jason S.; Solomon, Stephen B.; McNeil, Barbara J.; Baumann, Michaël; Gambhir, Sanjiv S.; Hricak, Hedvig; Weissleder, Ralph

doi:10.1016/s1470-2045(19)30821-6

Cited by 194 publications

(172 citation statements)

References 69 publications

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“…Subsequent development of theranostic agents for infection/inflammation (Velikyan 2018), prostate cancer (Eder et al 2014;Lenzo et al 2018;Ruangma et al 2018), C-X-C chemokine receptor type 4 (CXCR4) (Gourni et al 2011;Herrmann et al 2016) and, most recently, fibroblast activation protein inhibitors (FAPI) (Kratochwil et al 2019) is further driving demand and highlights the need for access to a reliable (and economical) supply of 68 Ga8 that is the focus of this paper. Analogous development of a reliable pipeline of therapeutic radionuclides is also an urgent need for the nuclear medicine community (Herrmann et al 2020), but beyond the scope of this article. Gallium-68 is usually eluted from a 68 Ge/ 68 Ga generator, and thus can be readily implemented in PET facilities that do not own a cyclotron.…”

Section: Introductionmentioning

confidence: 99%

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target

Rodnick

Sollert²,

Stark

et al. 2020

EJNMMI radiopharm. chem.

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Purpose To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2–0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use. Results The decay corrected yield of 68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined 66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3 was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). Conclusion Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators.

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Section: Introductionmentioning

confidence: 99%

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target

Rodnick

Sollert²,

Stark

et al. 2020

EJNMMI radiopharm. chem.

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“…Radiation Protection Dosimetry and Calibrations, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium; csvargas@sckcen.be. 2 In vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel, Jette, Belgium. 3 Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.…”

Section: Acknowledgementsmentioning

confidence: 99%

“…In the last decades, the application of personalized molecular radiotherapy using theragnostics has gained a lot of interest in nuclear medicine [1,2]. Theragnostic approaches aim to optimize molecular radiotherapy for individual patients using pre-therapeutic diagnostic imaging.…”

Section: Introductionmentioning

confidence: 99%

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theranostics

Vargas

Bauwens

Pooters

et al. 2020

Preprint

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Background: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu and 90Y.Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically-relevant theragnostic pairs: 131I/123I, 131I/124I, 177Lu/111In, 90Y/99mTc and 90Y/111In.Results: For 99mTc, 131I, and 177Lu, a small minority of measurements were not within ±5% range from the reference activity (percentage of measurements not within range: 99mTc: 6%, 131I: 14%, 177Lu: 24%) and almost none were outside ±10% range. However, for 111In, 123I, 124I and 90Y more than half of all measurements were not accurate within ±5% range (111In: 51%, 123I: 83%, 124I: 63%, 90Y: 61%) and not all were within ±10% margin (111In: 22%, 123I: 35%, 124I: 15%, 90Y: 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ±10%) for the investigated theragnostic pairs, in particular for 90Y/111In, 131I/123I and 90Y/99mTc.Conclusions: Our study shows that substantial over- or under-estimation of therapeutic patient doses are likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically-relevant radionuclide and sample geometry.

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Section: Introductionmentioning

confidence: 99%

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theragnostics

et al. 2020

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Background Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu, and 90Y. Methods In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radionuclide, a set of four samples comprising two clinical containers (10-mL glass vial and 3-mL syringe) with two filling volumes were measured. The reference value of each sample was determined by two certified radioactivity calibration centers (SCK CEN and JRC) using two secondary standard ionization chambers. The deviation in measured activity with respect to the reference value was determined for each radionuclide and each measurement geometry. In addition, the combined systematic deviation of activity measurements in a theragnostic setting was evaluated for 5 clinically relevant theragnostic pairs: 131I/123I, 131I/124I, 177Lu/111In, 90Y/99mTc, and 90Y/111In. Results For 99mTc, 131I, and 177Lu, a small minority of measurements were not within ± 5% range from the reference activity (percentage of measurements not within range: 99mTc, 6%; 131I, 14%; 177Lu, 24%) and almost none were outside ± 10% range. However, for 111In, 123I, 124I, and 90Y, more than half of all measurements were not accurate within ± 5% range (111In, 51%; 123I, 83%; 124I, 63%; 90Y, 61%) and not all were within ± 10% margin (111In, 22%; 123I, 35%; 124I, 15%; 90Y, 25%). A large variability in measurement accuracy was observed between radionuclide calibrator systems, type of sample container (vial vs syringe), and source-geometry calibration/correction settings used. Consequently, we observed large combined deviations (percentage deviation > ± 10%) for the investigated theragnostic pairs, in particular for 90Y/111In, 131I/123I, and 90Y/99mTc. Conclusions Our study shows that substantial over- or underestimation of therapeutic patient doses is likely to occur in a theragnostic setting due to errors in the assessment of radioactivity with radionuclide calibrators. These findings underline the importance of thorough validation of radionuclide calibrator systems for each clinically relevant radionuclide and sample geometry.

show abstract

Radiotheranostics: a roadmap for future development

Cited by 194 publications

References 69 publications

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theranostics

An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theragnostics

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