Radioiodinated recombinant human TSH: a novel radiopharmaceutical for thyroid cancer metastases detection.
The follow-up of differentiated thyroid cancer (DTC) is currently performed by serum Tg levels determination and whole body scan (WBS) with 131I. In this regard, the latter represents the main tool to localize metastatic tissue, but is characterized by the induction of severe hypothyroidism. Moreover, WBS displays poor sensitivity in poorly differentiated tumors due to a loss of iodine uptake capacity.


OBJECTIVE
In this study we describe an alternative tracer, radiolabeled rhTSH, for the diagnosis of non-iodine uptaking DTC metastases.


METHODS
rhTSH was iodinated with 125I or 123I using an enzymatic method with lactoperoxidase/glucose oxidase. In vitro stability of labeled compounds was assessed in saline and serum and in vivo studies were performed in tumor-bearing nude mice. Three mice were inoculated with ARO cells (TSH receptor negative) and three with PTC-1 cells (TSH receptor positive). After 25 days, mice were injected with 10 microg of 123I-rhTSH (100 microCi) and static images were acquired at 30 minutes, 1, 2, and 3 hours. Animals were then sacrificed and dissected for organ counting.


RESULTS
RhTSH was radioiodinated to high specific activity: 132.2 mCi/mg for 123I-rhTSH, 94.3 for 125I-rhTSH. In vitro stability tests revealed no significant release of radioiodine. A clear tumor uptake was detectable after 2 hours in all animals implanted with PTC-1.


CONCLUSIONS
Results obtained so far suggest that radiolabeled rhTSH might be a promising radiopharmaceutical for diagnosis and follow-up of DTC.
Corsetti
Frederica
F
University "La Sapienza," Rome, Rome, Italy.
Chianelli
Marco
M
Cornelissen
Bart
B
Van de Wiele
Christophe
C
D'Alessandria
Calogero
C
Slegers
Guido
G
Mather
Stephen J
SJ
Di Mario
Umberto
U
Filetti
Sebastiano
S
Scopinaro
Francesco
F
Signore
Alberto
A
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D013972:Thyrotropin / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D013972:Thyrotropin