Abstract
Purpose: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. Experimental Design: Albumin and liposomes were labeled with 64Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. Results: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10-8 and 1.3 × 10-8 cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. Conclusions: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 550-559 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 17 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 2011 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET. / Rygh, Cecilie B.; Qin, Shengping; Seo, Jai; Mahakian, Lisa M.; Zhang, Hua; Adamson, Roger; Chen, Jane Q.; Borowsky, Alexander D; Cardiff, Robert; Reed, Rolf K.; Curry, Fitz Roy E; Ferrara, Katherine W.
In: Clinical Cancer Research, Vol. 17, No. 3, 01.02.2011, p. 550-559.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET
AU - Rygh, Cecilie B.
AU - Qin, Shengping
AU - Seo, Jai
AU - Mahakian, Lisa M.
AU - Zhang, Hua
AU - Adamson, Roger
AU - Chen, Jane Q.
AU - Borowsky, Alexander D
AU - Cardiff, Robert
AU - Reed, Rolf K.
AU - Curry, Fitz Roy E
AU - Ferrara, Katherine W.
PY - 2011/2/1
Y1 - 2011/2/1
N2 - Purpose: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. Experimental Design: Albumin and liposomes were labeled with 64Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. Results: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10-8 and 1.3 × 10-8 cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. Conclusions: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability.
AB - Purpose: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. Experimental Design: Albumin and liposomes were labeled with 64Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. Results: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10-8 and 1.3 × 10-8 cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. Conclusions: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability.
UR - http://www.scopus.com/inward/record.url?scp=79551704041&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551704041&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-10-2049
DO - 10.1158/1078-0432.CCR-10-2049
M3 - Article
C2 - 21106723
AN - SCOPUS:79551704041
VL - 17
SP - 550
EP - 559
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 3
ER -