[64Cu]XYIMSR-06

A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma

Il Minn, Soo Min Koo, Hye Soo Lee, Mary Elizabeth Brummet, Steven Rowe, Michael Gorin, Polina Sysa-Shah, William D. Lewis, Hye Hyun Ahn, Yuchuan Wang, Sangeeta Ray, Ronnie Mease, Sridhar Nimmagadda, Mohamad E Allaf, Martin Gilbert Pomper, Xing Yang

Research output: Contribution to journalArticle

Abstract

Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1-8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.

Original languageEnglish (US)
Pages (from-to)56471-56479
Number of pages9
JournalOncotarget
Volume7
Issue number35
DOIs
StatePublished - 2016

Fingerprint

Renal Cell Carcinoma
Positron-Emission Tomography
Ligands
Neoplasms
Kidney
Muscles
Injections
Kidney Neoplasms
Carbonic Anhydrase IX
Radioactivity
Pharmacokinetics
Molecular Weight
Enzymes

Keywords

  • Carbonic anhydrase IX
  • Copper-64
  • Molecular imaging
  • Positron emission tomography
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology

Cite this

[64Cu]XYIMSR-06 : A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma. / Minn, Il; Koo, Soo Min; Lee, Hye Soo; Brummet, Mary Elizabeth; Rowe, Steven; Gorin, Michael; Sysa-Shah, Polina; Lewis, William D.; Ahn, Hye Hyun; Wang, Yuchuan; Ray, Sangeeta; Mease, Ronnie; Nimmagadda, Sridhar; Allaf, Mohamad E; Pomper, Martin Gilbert; Yang, Xing.

In: Oncotarget, Vol. 7, No. 35, 2016, p. 56471-56479.

Research output: Contribution to journalArticle

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title = "[64Cu]XYIMSR-06: A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma",
abstract = "Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95{\%} of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5{\%} (n=5) and specific activities of 4.1-8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3{\%} injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.",
keywords = "Carbonic anhydrase IX, Copper-64, Molecular imaging, Positron emission tomography, Renal cell carcinoma",
author = "Il Minn and Koo, {Soo Min} and Lee, {Hye Soo} and Brummet, {Mary Elizabeth} and Steven Rowe and Michael Gorin and Polina Sysa-Shah and Lewis, {William D.} and Ahn, {Hye Hyun} and Yuchuan Wang and Sangeeta Ray and Ronnie Mease and Sridhar Nimmagadda and Allaf, {Mohamad E} and Pomper, {Martin Gilbert} and Xing Yang",
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T2 - A dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma

AU - Minn, Il

AU - Koo, Soo Min

AU - Lee, Hye Soo

AU - Brummet, Mary Elizabeth

AU - Rowe, Steven

AU - Gorin, Michael

AU - Sysa-Shah, Polina

AU - Lewis, William D.

AU - Ahn, Hye Hyun

AU - Wang, Yuchuan

AU - Ray, Sangeeta

AU - Mease, Ronnie

AU - Nimmagadda, Sridhar

AU - Allaf, Mohamad E

AU - Pomper, Martin Gilbert

AU - Yang, Xing

PY - 2016

Y1 - 2016

N2 - Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1-8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.

AB - Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1-8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.

KW - Carbonic anhydrase IX

KW - Copper-64

KW - Molecular imaging

KW - Positron emission tomography

KW - Renal cell carcinoma

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