Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer.

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.

A pilot pharmacokinetic and immunoscintigraphic study with the technetium-99m-labeled monoclonal antibody BC-1 directed against oncofetal fibronectin in patients with brain tumors.

BACKGROUND: Preliminary experiments in an animal model have shown the favorable tumor targeting potential in vivo of radiolabeled BC-1, an immunoglobulin (Ig)G1 monoclonal antibody (MoAb) that recognizes the human fibronectin isoform (B+) containing the ED-B oncofetal domain. This antigen has extremely restricted distribution in normal adult tissues. Instead, it is highly expressed in fetal and tumor tissues, especially in high grade astrocytomas and malignant gliomas of the brain, in which the process of neoangiogenesis linked to tumor growth is particularly important. METHODS: This study was carried out with five patients who had malignant brain tumors (four gliomas and one malignant angioblastic meningioma). The BC-1 MoAb was labeled with technetium-99m (99mTc) by MDP transchelation. Planar and single photon emission computed tomography (SPECT) imaging was acquired at 4-6 and 20 hours after intravenous injection of about 450 MBq/0.2 mg 99mTc-BC-1 and was compared with the nonspecific indicator of blood-brain barrier disruption, 99mTc-diethylenetriamine pentaacetic acid (DTPA). Plasma pharmacokinetic analysis was based on serial blood sampling. All patients underwent potentially curative surgery at the end of the study. RESULTS: The plasma clearance curves were biexponential, with average T(1/2) values of 2-4 hours and 28-33 hours, respectively. 99mTc-BC-1 showed very low nonspecific uptake in the bone marrow, liver, and spleen. Planar and SPECT imaging with 99mTc-BC-1 visualized brain tumors in all patients, with a pattern of intratumor distribution that specifically identified areas of peripheral tumor growth more accurately than the nonspecific indicator, 99mTc-DTPA. Tumor uptake of 99mTc-BC-1 was correlated with the expression of the specific oncofetal fibronectin, as shown by immunohistochemistry on surgical samples. CONCLUSIONS: These results indicate the diagnostic potential of MoAb 99mTc-BC-1 for immunoscintigraphy in cancer patients, at least when neoangiogenesis induced by cancer is particularly important.