Impact of radioactive impurities on Yttrium-90 glass microsphere quantitation

Introduction: Glass Yttrium-90 microspheres are produced with known radionuclide impurities. However, some of these impurities (most importantly Yttrium-88 and Scandium-46), can have an outsized impact on dose calibrator and readings. Thus, even what might be considered negligibly small impurity fractions from a dosimetric viewpoint, can cause significant overestimates in the amount of ⁹⁰Y activity present in a given sample.

Methods: In this work we reviewed physical considerations that will result in asymmetric errors in quantitation from ⁹⁰Y impurities, and estimate their typical and potential impact on clinical utilization. In an analysis by Metyko and colleagues it was shown that ⁹⁰Y glass microspheres are produced with up to 17 known contaminants ¹. Of these, we identified ⁸⁸Y and ⁴⁶Sc to be of particular concern for their impact on ⁹⁰Y dose measurements. ⁸⁸Y has major gamma emissions at energies of 0.898 MeV (93.70%) and 1.836 MeV (99.20%), while ⁴⁶Sc has gammas at 0.8893 MeV (99.98%) and 1.1205 MeV (99.99%). These high energy gammas are of concern because of their impact on the activity measurement when an ion chamber is used. Based on these emissions, we can project that an R-series Capintec dose calibrator, for example, will be 82.2 times more sensitive to ⁸⁸Y than it is to ⁹⁰Y, while ⁴⁶Sc is 67.7 times more sensitive. ⁸⁸Y impurities can also impact ⁹⁰Y dosimetry in post implantation PET imaging. ⁸⁸Y has a positron abundance of just 0.21%, but this is still 65.9 times that of ⁹⁰Y. Thus, we can anticipate that even small amounts of this contaminate could have a large impact on PET quantitation.

Upon request, Boston Scientific has provided us with documentation on the TheraSphere byproducts (manufacturer reference PI-745103-AB). This data sheet lists typical concentrations of byproduct materials based on 45 consecutive production lots (acquired after January 2010 and cited as "data on file") and indicates that these estimates were independently corroborated by the National Institute of Standards and Technology. Using existing resources, we can calculate the anticipated impact of ⁹⁰Y impurities on dose calibrator readings – from abundant high energy gamma emissions, and PET quantitation – from high positron emission fractions.

Results: Given typical levels of impurities reported in the literature, we project the impact on dose calibrator measurements to be less than 2.5% within the 12-day label use period (see figures 1-3). The errors in PET measurements would be similarly small over this time. However, the maximum impurities allowed by the manufacturer based on their product specification can result in dose calibrator and PET errors of over 10% within this 12-day period. Moreover, if measurements were to be made beyond the 12-day use-by period, these errors would get exponentially larger, increasing with time post-production at a rate close to that of ⁹⁰Y’s 2.67-day half-life (note: ⁸⁸Y and ⁴⁶Sc half-lives are 106.65 and 83.1 days, respectively).

Conclusions: To our knowledge, quantitative aspects of radionuclide impurities in glass microspheres have not been documented in the field, and they have the potential to affect dosimetry and dose correlations. As activity quantitation for dosimetry and its correlations with outcome becomes more prevalent, this aspect of quantitation may remain unaccounted for in dosimetry studies. While typical levels of impurities appear acceptable, it should be noted that "max permissible" levels can be of consequence, and it is worth noting that there is minimal independent monitoring of impurity levels within the field.

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