99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen: pharmacokinetics and biodistribution studies in healthy subjects and patients with metastatic prostate cancer.

Autor:	Vallabhajosula S; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York svallabh@med.cornell.edu., Nikolopoulou A; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York., Babich JW; Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts; and., Osborne JR; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York., Tagawa ST; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York., Lipai I; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York., Solnes L; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York., Maresca KP; Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts; and., Armor T; Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts; and., Joyal JL; Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts; and., Crummet R; Molecular Insight Pharmaceuticals, Inc., Cambridge, Massachusetts; and., Stubbs JB; Radiation Dosimetry Systems, Inc, Alpharetta, Georgia., Goldsmith SJ; New York Presbyterian Hospital and Weill Cornell Medical College, New York, New York.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2014 Nov; Vol. 55 (11), pp. 1791-8. Date of Electronic Publication: 2014 Oct 23.
DOI:	10.2967/jnumed.114.140426
Abstrakt:	Unlabelled: Prostate-specific membrane antigen (PSMA) is a well-established target for developing radiopharmaceuticals for imaging and therapy of prostate cancer (PCa). We have recently reported that novel (99m)Tc-labeled small-molecule PSMA inhibitors bind with high affinity to PSMA-positive tumor cells in vitro and localize in PCa xenografts. This study reports the first, to our knowledge, human data in men with metastatic PCa and in healthy male subjects. Methods: Under an exploratory investigational new drug, using a cross-over design, we compared the pharmacokinetics, biodistribution, and tumor uptake of (99m)Tc-MIP-1404 and (99m)Tc-MIP-1405 in 6 healthy men and 6 men with radiographic evidence of metastatic PCa. Whole-body images were obtained at 10 min and 1, 2, 4, and 24 h. SPECT was performed between 3 and 4 h after injection. Results: Both agents cleared the blood rapidly, with MIP-1404 demonstrating significantly lower urinary activity (7%) than MIP-1405 (26%). Both agents showed persistent uptake in the salivary, lacrimal, and parotid glands. Uptake in the liver and kidney was acceptable for imaging at 1-2 h. In men with PCa, both agents rapidly localized in bone and lymph node lesions as early as 1 h. SPECT demonstrated excellent lesion contrast. Good correlation was seen with bone scanning; however, more lesions were demonstrated with (99m)Tc-MIP-1404 and (99m)Tc-MIP-1405. The high-contrast images exhibited tumor-to-background ratios from 3:1 to 9:1 at 4 and 20 h. Conclusion: Compared with the standard-of-care bone scanning, (99m)Tc-MIP-1404 and (99m)Tc-MIP-1405 identified most bone metastatic lesions and rapidly detected soft-tissue PCa lesions including subcentimeter lymph nodes. Because (99m)Tc-MIP-1404 has minimal activity in the bladder, further work is planned to correlate imaging findings with histopathology in patients with high-risk metastatic PCa. (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)
Databáze:	MEDLINE
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