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Imaging of lymph node micrometastases using an oncolytic herpes virus and [F]FEAU PET.

Brader P, Kelly K, Gang S, Shah JP, Wong RJ, Hricak H, Blasberg RG, Fong Y, Gil Z - PLoS ONE (2009)

Bottom Line: Presence of virus-infected tumor cells was successfully imaged with [(18)F]FEAU-PET, that identified 8 out of 8 tumor-positive nodes.There was no overlap between radioactivity levels (lymph node to surrounding tissue ratio) of tumor-positive and tumor-negative lymph nodes.A new approach for imaging SLN metastases using NV1023 and [(18)F]FEAU-PET was successful in a murine model.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

ABSTRACT

Background: In patients with melanoma, knowledge of regional lymph node status provides important information on outlook. Since lymph node status can influence treatment, surgery for sentinel lymph node (SLN) biopsy became a standard staging procedure for these patients. Current imaging modalities have a limited sensitivity for detection of micrometastases in lymph nodes and, therefore, there is a need for a better technique that can accurately identify occult SLN metastases.

Methodology/principal findings: B16-F10 murine melanoma cells were infected with replication-competent herpes simplex virus (HSV) NV1023. The presence of tumor-targeting and reporter-expressing virus was assessed by [(18)F]-2'-fluoro-2'-deoxy-1-beta-D-beta-arabinofuranosyl-5-ethyluracil ([(18)F]FEAU) positron emission tomography (PET) and confirmed by histochemical assays. An animal foot pad model of melanoma lymph node metastasis was established. Mice received intratumoral injections of NV1023, and 48 hours later were imaged after i.v. injection of [(18)F]FEAU. NV1023 successfully infected and provided high levels of lacZ transgene expression in melanoma cells. Intratumoral injection of NV1023 resulted in viral trafficking to melanoma cells that had metastasized to popliteal and inguinal lymph nodes. Presence of virus-infected tumor cells was successfully imaged with [(18)F]FEAU-PET, that identified 8 out of 8 tumor-positive nodes. There was no overlap between radioactivity levels (lymph node to surrounding tissue ratio) of tumor-positive and tumor-negative lymph nodes.

Conclusion/significance: A new approach for imaging SLN metastases using NV1023 and [(18)F]FEAU-PET was successful in a murine model. Similar studies could be translated to the clinic and improve the staging and management of patients with melanoma.

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Related in: MedlinePlus

Radioactivity measurements and lymph node weight.(A) Lymph node-to-surrounding tissue radioactivity ratios obtained from the [18F]FEAU PET images in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.603; y =  74.0x+0.939 and 10 negative nodes (▵) R2 = 0.035; y = 2.62x+1.080). (B) Ex vivo radioactivity measurements from excised lymph nodes. Lymph node radioactivity (%ID/g) in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.328; y = 14.4x+0.214 and 20 negative nodes (▵) R2 = 0.054; y = −1.40x+0.108).
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pone-0004789-g006: Radioactivity measurements and lymph node weight.(A) Lymph node-to-surrounding tissue radioactivity ratios obtained from the [18F]FEAU PET images in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.603; y =  74.0x+0.939 and 10 negative nodes (▵) R2 = 0.035; y = 2.62x+1.080). (B) Ex vivo radioactivity measurements from excised lymph nodes. Lymph node radioactivity (%ID/g) in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.328; y = 14.4x+0.214 and 20 negative nodes (▵) R2 = 0.054; y = −1.40x+0.108).

Mentions: Immediately after imaging, the lymph nodes were excised, weighed and radioactivity analyzed in a gamma counter prior to histological examination. There was a clear separation in radioactivity levels (%ID/g) between tumor-positive (n = 8) and tumor-negative (n = 20) nodes with no overlap (Figure 6B). All positive lymph nodes had radioactivity values at least two standard deviations above the negative nodes. The radioactivity level profile is similar to that obtained from the ROI analysis of the microPET images (Figure 6).


Imaging of lymph node micrometastases using an oncolytic herpes virus and [F]FEAU PET.

Brader P, Kelly K, Gang S, Shah JP, Wong RJ, Hricak H, Blasberg RG, Fong Y, Gil Z - PLoS ONE (2009)

Radioactivity measurements and lymph node weight.(A) Lymph node-to-surrounding tissue radioactivity ratios obtained from the [18F]FEAU PET images in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.603; y =  74.0x+0.939 and 10 negative nodes (▵) R2 = 0.035; y = 2.62x+1.080). (B) Ex vivo radioactivity measurements from excised lymph nodes. Lymph node radioactivity (%ID/g) in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.328; y = 14.4x+0.214 and 20 negative nodes (▵) R2 = 0.054; y = −1.40x+0.108).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2651472&req=5

pone-0004789-g006: Radioactivity measurements and lymph node weight.(A) Lymph node-to-surrounding tissue radioactivity ratios obtained from the [18F]FEAU PET images in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.603; y =  74.0x+0.939 and 10 negative nodes (▵) R2 = 0.035; y = 2.62x+1.080). (B) Ex vivo radioactivity measurements from excised lymph nodes. Lymph node radioactivity (%ID/g) in NV1023-treated animals versus lymph node weight (8 positive nodes (♦) R2 = 0.328; y = 14.4x+0.214 and 20 negative nodes (▵) R2 = 0.054; y = −1.40x+0.108).
Mentions: Immediately after imaging, the lymph nodes were excised, weighed and radioactivity analyzed in a gamma counter prior to histological examination. There was a clear separation in radioactivity levels (%ID/g) between tumor-positive (n = 8) and tumor-negative (n = 20) nodes with no overlap (Figure 6B). All positive lymph nodes had radioactivity values at least two standard deviations above the negative nodes. The radioactivity level profile is similar to that obtained from the ROI analysis of the microPET images (Figure 6).

Bottom Line: Presence of virus-infected tumor cells was successfully imaged with [(18)F]FEAU-PET, that identified 8 out of 8 tumor-positive nodes.There was no overlap between radioactivity levels (lymph node to surrounding tissue ratio) of tumor-positive and tumor-negative lymph nodes.A new approach for imaging SLN metastases using NV1023 and [(18)F]FEAU-PET was successful in a murine model.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.

ABSTRACT

Background: In patients with melanoma, knowledge of regional lymph node status provides important information on outlook. Since lymph node status can influence treatment, surgery for sentinel lymph node (SLN) biopsy became a standard staging procedure for these patients. Current imaging modalities have a limited sensitivity for detection of micrometastases in lymph nodes and, therefore, there is a need for a better technique that can accurately identify occult SLN metastases.

Methodology/principal findings: B16-F10 murine melanoma cells were infected with replication-competent herpes simplex virus (HSV) NV1023. The presence of tumor-targeting and reporter-expressing virus was assessed by [(18)F]-2'-fluoro-2'-deoxy-1-beta-D-beta-arabinofuranosyl-5-ethyluracil ([(18)F]FEAU) positron emission tomography (PET) and confirmed by histochemical assays. An animal foot pad model of melanoma lymph node metastasis was established. Mice received intratumoral injections of NV1023, and 48 hours later were imaged after i.v. injection of [(18)F]FEAU. NV1023 successfully infected and provided high levels of lacZ transgene expression in melanoma cells. Intratumoral injection of NV1023 resulted in viral trafficking to melanoma cells that had metastasized to popliteal and inguinal lymph nodes. Presence of virus-infected tumor cells was successfully imaged with [(18)F]FEAU-PET, that identified 8 out of 8 tumor-positive nodes. There was no overlap between radioactivity levels (lymph node to surrounding tissue ratio) of tumor-positive and tumor-negative lymph nodes.

Conclusion/significance: A new approach for imaging SLN metastases using NV1023 and [(18)F]FEAU-PET was successful in a murine model. Similar studies could be translated to the clinic and improve the staging and management of patients with melanoma.

Show MeSH
Related in: MedlinePlus