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Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts.

Publication ,  Journal Article
Blocker, SJ; Douglas, KA; Polin, LA; Lee, H; Hendriks, BS; Lalo, E; Chen, W; Shields, AF
Published in: Theranostics
2017

Liposomes (LP) deliver drug to tumors due to enhanced permeability and retention (EPR). LP were labeled with 64Cu for positron emission tomography (PET) to image tumor localization. Bevacizumab (bev), a VEGF targeted antibody, may modify LP delivery by altering tumor EPR and this change can also be imaged. Objective: Assess the utility of 64Cu-labeled LP for PET in measuring altered LP delivery early after treatment with bev. Methods: HT-29 human colorectal adenocarcinoma tumors were grown subcutaneously in SCID mice. Empty LP MM-DX-929 (Merrimack Pharmaceuticals, Inc. Cambridge, MA) were labeled with 64CuCl2 chelated with 4-DEAP-ATSC. Tumor-bearing mice received ~200-300 μCi of 64Cu-MM-DX-929 and imaged with microPET. All mice were scanned before and after the treatment period, in which half of the mice received bev for one week. Scans were compared for changes in LP accumulation during this time. Initially, tissues were collected after the second PET for biodistribution measurements and histological analysis. Subsequent groups were divided for further treatment. Tumor growth following bev treatment, with or without LP-I, was assessed compared to untreated controls. Results: PET scans of untreated mice showed increased uptake of 64Cu-MM-DX-929, with a mean change in tumor SUVmax of 43.9%±6.6% (n=10) after 7 days. Conversely, images of treated mice showed that liposome delivery did not increase, with changes in SUVmax of 7.6%±4.8% (n=12). Changes in tumor SUVmax were significantly different between both groups (p=0.0003). Histology of tumor tissues indicated that short-term bev was able to alter vessel size. Therapeutically, while bev monotherapy, LP-I monotherapy, and treatment with bev followed by LP-I all slowed HT-29 tumor growth compared to controls, combination provided no therapeutic benefit. Conclusions: PET with tracer LP 64Cu-MM-DX-929 can detect significant differences in LP delivery to colon tumors treated with bev when compared to untreated controls. Imaging with 64Cu-MM-DX-929 is sensitive enough to measure drug-induced changes in LP localization which can have an effect on outcomes of treatment with LP.

Duke Scholars

Published In

Theranostics

DOI

EISSN

1838-7640

Publication Date

2017

Volume

7

Issue

17

Start / End Page

4229 / 4239

Location

Australia

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Positron-Emission Tomography
  • Mice, SCID
  • Mice
  • Liposomes
  • Irinotecan
  • Humans
  • HT29 Cells
  • Copper Radioisotopes
  • Colonic Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Blocker, S. J., Douglas, K. A., Polin, L. A., Lee, H., Hendriks, B. S., Lalo, E., … Shields, A. F. (2017). Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts. Theranostics, 7(17), 4229–4239. https://doi.org/10.7150/thno.21688
Blocker, Stephanie J., Kirk A. Douglas, Lisa Anne Polin, Helen Lee, Bart S. Hendriks, Enxhi Lalo, Wei Chen, and Anthony F. Shields. “Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts.Theranostics 7, no. 17 (2017): 4229–39. https://doi.org/10.7150/thno.21688.
Blocker SJ, Douglas KA, Polin LA, Lee H, Hendriks BS, Lalo E, et al. Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts. Theranostics. 2017;7(17):4229–39.
Blocker, Stephanie J., et al. “Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts.Theranostics, vol. 7, no. 17, 2017, pp. 4229–39. Pubmed, doi:10.7150/thno.21688.
Blocker SJ, Douglas KA, Polin LA, Lee H, Hendriks BS, Lalo E, Chen W, Shields AF. Liposomal 64Cu-PET Imaging of Anti-VEGF Drug Effects on Liposomal Delivery to Colon Cancer Xenografts. Theranostics. 2017;7(17):4229–4239.

Published In

Theranostics

DOI

EISSN

1838-7640

Publication Date

2017

Volume

7

Issue

17

Start / End Page

4229 / 4239

Location

Australia

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Positron-Emission Tomography
  • Mice, SCID
  • Mice
  • Liposomes
  • Irinotecan
  • Humans
  • HT29 Cells
  • Copper Radioisotopes
  • Colonic Neoplasms