Optimised labeling, preclinical and initial clinical aspects of CCK-2 receptor-targeting with 3 radiolabeled peptides.

Medullary thyroid carcinoma (MTC) expresses CCK-2 receptors. (111)In-labeled DOTA-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH(2) (DOTA-MG11), DOTA-DAsp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH(2) (DOTA-CCK), and (99m)Tc-labeled N(4)-Gly-DGlu-(Glu)(5)-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH(2) ((99m)Tc-Demogastrin 2) are analogs developed for CCK-2 receptor-targeted scintigraphy. All 3 radiolabeled analogs were selected on the basis of their high CCK-2 receptor affinity and their good in vitro serum stability, with in vitro serum t(1/2) values of several hours. Radiolabeling of DOTA-peptides with (111)In requires a heating procedure, typically in the range of 80 degrees -100 degrees C up to 30 min. Following this procedure with DOTA-MG11 resulted in a >98 % incorporation of (111)In, however, with a radiochemical purity (RCP) of <50 %. The decrease in RCP was found to be due to oxidation of the methionine residue in the molecule. Moreover, this oxidized compound lost its CCK-2 receptor affinity. Therefore, conditions during radiolabeling were optimised: labeling of DOTA-MG11 and DOTA-CCK with (111)In involved 5 min heating at 80 degrees C and led to an incorporation of (111)In of >98 %. In addition, all analogs were radiolabeled in the presence of quenchers to prevent radiolysis and oxidation resulting in a RCP of >90 %. All 3 radiolabeled analogs were i.v. administered to 6 MTC patients: radioactivity cleared rapidly by the kidneys, with no significant differences in the excretion pattern of the 3 radiotracers. All 3 radiolabeled analogs exhibited a low in vivo stability in patients, as revealed during analysis of blood samples, with the respective t(1/2) found in the order of minutes. In patient blood, the rank of radiopeptide in vivo stability was: (99m)Tc-Demogastrin 2 (t(1/2) 10-15 min)>(111)In-DOTA-CCK (t(1/2) approximately 5-10 min)>(111)In-DOTA-MG11 (t(1/2)<5 min).

Tc-99m sestamibi before and during treatment in a patient with sarcoidosis and persistent hyperparathyroidism.

PURPOSE: Tc-99m sestamibi (MIBI) uptake in pulmonary sarcoidosis has been reported, but it has never been studied before and during treatment with glucocorticoids. METHODS: The authors performed MIBI scintigraphy and somatostatin receptor scintigraphy in a patient with sarcoidosis of the mediastinum, lungs, and liver and who had persistent hyperparathyroidism after unsuccessful neck exploration. RESULTS: Somatostatin receptor scintigraphy showed high mediastinal and pulmonary uptake in a pattern characteristic of sarcoidosis. Sustained MIBI uptake occurred in the same, although smaller, region. After the diagnosis was confirmed by liver biopsy, the patient was treated with glucocorticoids. Repeated MIBI scintigraphy showed that the uptake in the mediastinum had clearly decreased. CONCLUSIONS: This decrease of MIBI uptake in the mediastinal lymph nodes with therapy may imply that MIBI can be used to assess the response to treatment in sarcoidosis. Perhaps a relation exists between MIBI uptake at the moment of diagnosis and prognosis. Further studies in more patients are needed to evaluate the role of MIBI in the management of sarcoidosis.