Dosing Therapeutic Radiopharmaceuticals in Obese Patients

Abstract

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.

Keywords: obesity; pharmacokinetics; radiopharmaceutical.

Figure 1

Dose simulation for radium-223 (²²³Ra) at 55 kBq/kg. The gray horizontal line represents the registered dose for a 70 kg patient (55 kBq/kg), while the black horizontal line represents the maximum tolerated dose for a 70 kg patient (276 kBq/kg). The BMI was calculated for a patient with average height (1.70 m). The intercept at 351 kg shows the weight at which the registered dose is equal to the maximum tolerated dose when administered to a 70 kg patient. This corresponds to a patient with a BMI of 121 kg/m².

Figure 2

Dose simulation for samarium-153 (¹⁵³Sm) at 37 kBq/kg. The black horizontal line represents the recommended dose for a 70 kg patient (37 kBq/kg), while the gray horizontal line represents the maximum tolerated dose for a 70 kg patient (93 kBq/kg). The BMI was calculated for a patient with average height (1.70 m). The intercept at 176 kg shows the weight at which the registered dose is equal to the maximum tolerated dose when administered to a 70 kg patient. This corresponds to a patient with a BMI of 61 kg/m².