Journal article
Preclinical development of a neutral, estrogen receptor-targeted, tridentate Tc-99m(I)-estradiol-pyridin-2-yl hydrazine derivative for imaging of breast and endometrial cancers
The Journal of nuclear medicine (1978), Vol.49(6), pp.978-986
06/01/2008
DOI: 10.2967/jnumed.107.048546
PMCID: PMC2435083
PMID: 18483091
Abstract
Breast and endometrial cancers are the most common invasive malignancies in women, with more than 217,000 new diagnoses per year in the United States. These cancers are often classified into 2 subtypes based on the expression of the classical estrogen receptor. In this study, we describe a new structural class of neutral tridentate Tc-99m(I)-estradiol-pyridin-2-yl hydrazine derivatives for potential use in breast and endometrial cancer imaging. Methods: The Tc-99m(I)-estradiol-pyridin-2-yl hydrazine derivative was synthesized via the Sonogashira cross-coupling reaction and radiolabeled via the tricarbonyl approach. Radiochemical purity was assessed by high-performance liquid chromatography. Cell-binding studies were performed with human breast adenocarcinoma MCF-7 cells. The in vivo biodistribution of the Tc-99m(I) derivative was evaluated in virgin female C57BL/6 mice in defined phases of the estrous cycle. Biodistribution and SPECT/CT studies were performed with mice bearing MCF-7 and primary human endometrial tumors. Results: Radiochemical analysis demonstrated that the postpurification purity of the Tc-99m(I)-estradiol-pyridin-2-yl hydrazine derivative was >= 95%, with a specific activity of Tc-99m of 47.5 TBq/mmol. Cell-binding studies yielded a dissociation constant (mean +/- SEM) of 11 +/- 1.5 nM. In vivo studies revealed that receptor-mediated uptake was present in all phases of the estrous cycle in reproductive organs and mammary glands but was highest during the diestrous phase of the estrous cycle. Despite high nonspecific uptake in the liver, significant receptor- mediated uptake was observed in target tissues and estrogen receptor-expressing tumors (0.67% for MCF-7 tumors and 0.77% for endometrial tumors). Tumor uptake was reduced by approximately 50% on coinjection with 17 beta-estradiol. Conclusion: We have characterized a novel neutral tridentate Tc-99m(I)-estradiol-pyridin-2-yl hydrazine derivative for potential use in breast and endometrial cancer imaging. This study represents the first step on a path toward the design of estrogen-based Tc-labeled tracers with improved targeting and SPECT imaging characteristics.
Details
- Title: Subtitle
- Preclinical development of a neutral, estrogen receptor-targeted, tridentate Tc-99m(I)-estradiol-pyridin-2-yl hydrazine derivative for imaging of breast and endometrial cancers
- Creators
- Tapan K. Nayak - Univ New Mexico, Dept Cell Biol & Physiol, Sch Med, Hlth Sci Ctr, Albuquerque, NM 87131 USAHelen J. Hathaway - Univ New Mexico, Dept Cell Biol & Physiol, Sch Med, Hlth Sci Ctr, Albuquerque, NM 87131 USAChinnasamy Ramesh - New Mexico State Univ, Dept Chem & Biochem, Las Cruces, NM 88003 USAJeffrey B. Arterburn - Univ New Mexico, Hlth Sci Ctr, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USADonghai Dai - University of Iowa, Obstetrics and GynecologyLarry A. Sklar - University of New MexicoJeffrey P. Norenberg - University of New MexicoEric R. Prossnitz - Univ New Mexico, Dept Cell Biol & Physiol, Sch Med, Hlth Sci Ctr, Albuquerque, NM 87131 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of nuclear medicine (1978), Vol.49(6), pp.978-986
- Publisher
- Soc Nuclear Medicine Inc
- DOI
- 10.2967/jnumed.107.048546
- PMID
- 18483091
- PMCID
- PMC2435083
- ISSN
- 0161-5505
- eISSN
- 1535-5667
- Number of pages
- 9
- Grant note
- U54 MH074425; MH074425 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01 CA118743; R01 CA118743-01A2; CA116662; R01 CA116662-02; P30 CA118100; CA127731; R01 CA127731; R01 CA116662 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA118100 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) S06GM008136 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) U54MH074425 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) S06 GM008136; GM08136 / NIGMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 06/01/2008
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983557560802771
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