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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

In situ photograph of lymph node metastasis from melanoma.B16-F10 melanoma cells were injected into the right footpad of C57BL/6J-TyrC-2J/J mice. Twenty days after cancer cell injection, melanoma metastases were detected in the right popliteal area.
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pone-0004789-g003: In situ photograph of lymph node metastasis from melanoma.B16-F10 melanoma cells were injected into the right footpad of C57BL/6J-TyrC-2J/J mice. Twenty days after cancer cell injection, melanoma metastases were detected in the right popliteal area.

Mentions: Malignant melanoma tumors were established in the right foot pad of 30 C57BL/6J-TyrC-2J/J albino mice by direct injection of 2×105 melanoma cells (B16-F10). Twenty days after cancer cell injection, approximately 50% of the animals had evidence of subcentimeter black-colored lymph nodes in their popliteal area (Figure 3).


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)

In situ photograph of lymph node metastasis from melanoma.B16-F10 melanoma cells were injected into the right footpad of C57BL/6J-TyrC-2J/J mice. Twenty days after cancer cell injection, melanoma metastases were detected in the right popliteal area.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2651472&req=5

pone-0004789-g003: In situ photograph of lymph node metastasis from melanoma.B16-F10 melanoma cells were injected into the right footpad of C57BL/6J-TyrC-2J/J mice. Twenty days after cancer cell injection, melanoma metastases were detected in the right popliteal area.
Mentions: Malignant melanoma tumors were established in the right foot pad of 30 C57BL/6J-TyrC-2J/J albino mice by direct injection of 2×105 melanoma cells (B16-F10). Twenty days after cancer cell injection, approximately 50% of the animals had evidence of subcentimeter black-colored lymph nodes in their popliteal area (Figure 3).

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