title: Bone marrow dosimetry and safety of high 131I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer.
abstract: Recombinant human thyroid-stimulating hormone (rhTSH) recently was introduced as a radioiodine administration adjunct that avoids levothyroxine (LT-4) withdrawal and resultant hypothyroidism. The pharmacokinetics of 131I after rhTSH administration are known to differ from those after LT-4 withdrawal but are largely nondelineated in the radioiodine therapy setting. We therefore sought to calculate the red marrow absorbed dose of high therapeutic activities of 131I given after rhTSH administration to patients with metastatic or inoperable locally recurrent differentiated thyroid cancer. We also sought to evaluate the clinical and laboratory effects of this therapy on the bone marrow.
  
  
  METHODS
  Fourteen consecutive patients received in total 17 131I treatments (7.4 GBq). Blood and urine samples were obtained at fixed intervals, and their activities were measured in a well counter. Based on blood activity, renal clearance of the activity, and residence times in red marrow and the remainder of the body, the red marrow absorbed dose was calculated using the MIRD schema. Additionally, we monitored for potential hematologic toxicity and compared platelet counts before and 3 mo after treatment.
  
  
  RESULTS
  The mean +/- SD absorbed dose per unit of administered (131)I in the red marrow was 0.16 +/- 0.07 mGy/MBq. The corresponding total red marrow absorbed dose was 1.15 +/- 0.52 Gy (range, 0.28-1.91 Gy). In none of the patients was hematologic toxicity observed. The mean +/- SD platelet count (n = 13 treatments) was 243 +/- 62 x 10(9)/L before treatment and 233 +/- 87 x 10(9)/L 3 mo later, a slight and statistically insignificant decrease. After rhTSH-aided administration of high activities of 131I, the bone marrow absorbed dose remained under 2 Gy, the level long considered the safety threshold for all radioiodine therapy.
  
  
  CONCLUSIONS
  Our specific findings imply that when clinically warranted, rhTSH should allow an increase in the therapeutic radioiodine activity. Such an increase might improve efficacy while preserving safety and tolerability; this possibility should be assessed in further studies.
authors.affiliation: Department of Nuclear Medicine, Utrecht University Medical Center, Utrecht, The Netherlands. b.dekeizer@azu.nl
authors.forename: Bart
authors.initials: B
authors.lastname: de Keizer
authors.forename: Anne
authors.initials: A
authors.lastname: Hoekstra
authors.forename: Mark W
authors.initials: MW
authors.lastname: Konijnenberg
authors.forename: Filip
authors.initials: F
authors.lastname: de Vos
authors.forename: Bieke
authors.initials: B
authors.lastname: Lambert
authors.forename: Peter P
authors.initials: PP
authors.lastname: van Rijk
authors.forename: Cees J M
authors.initials: CJ
authors.lastname: Lips
authors.forename: John M H
authors.initials: JM
authors.lastname: de Klerk
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001822:Body Burden; D001853:Bone Marrow / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000528:radiation effects*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007273:Injections, Intramuscular; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D011835:Radiation Protection / Q000379:methods; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D018570:Risk Assessment / Q000379:methods*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D013972:Thyrotropin / Q000008:administration & dosage* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D013972:Thyrotropin