CLINICAL AND BIOLOGICAL BASIS OF 18F-FDG PET IN CANCER

Summary

Principal Investigator: Yuman Fong
Abstract: Colorectal cancer is a common disease entity and the liver represents the most common site of metastases for this cancer. Liver resection is the treatment of choice and the only potentially curative treatment. Extrahepatic disease represents a relative contraindication for resection. Often, patients brought to the operating room for liver resection are found to have additional intra-abdominal disease, cannot be resected, and are therefore subjected to a laparotomy for no benefit. Furthermore, in the majority of patients, tumor recurs due to residual disease undetected at the time of liver resection. Colorectal cancers are glucose avid and whole body positron emission scanning (PET) after administration of the glucose analogue 18F-fluorodeoxyglucose (18F- FDG) has been proposed as a sensitive non-invasive method for detecting metastatic colorectal cancer. Prior studies examining the use of this imagine modality have not systematically compared it to conventional imaging. A major goal of the current proposal is to examine the additional yield of 18F-FDG PET scanning compared with standard scanning modalities in this common clinical setting. The potential of this modality to change clinical therapy by detecting additional metastatic disease and reducing unnecessary surgery will be determined as well as its ability to direct more appropriate resections by finding additional resectable disease not seen by other imaging modalities. In this proposal, metastatic lesions in the liver will be resected, allowing a unique opportunity to determine the limits of detection of 18F-FDG PET scanning for metastatic colorectal tumor. This may have important therapeutic implications since others have proposed the use of whole body FDG- PET scanning to monitor therapeutic benefits and alter therapeutic course of chemotherapeutic and ablative therapies. Finally, glucose transport and glucose utilization by tumors have been correlated to local growth factor levels, tumor metabolism, and aggressiveness in other tumor types. Increased glucose transport and metabolism have been correlated to poor prognosis in other tumor.as. This proposed study allows direct correlation of 18F-FDG PET data with tissue measurements of glucose transport deoxyglucose phosphorylation, tumor proliferation, and long term patient prognosis. This allows correlation of FDG uptake as measured by PET in colorectal metastases to biologic determinants of tumor aggressiveness, and ultimately to clinical behavior of tumors. These studies will not only examine the prognostic implications of FDG-PET but also the biologic basis for prognostic influences. Thus, the specific goals of this application are to determine the clinical ability of 18F- FDG PET in the patient with hepatic colorectal metastases. We will attempt to determine the limits of detection of this modality, to correlate the FDG uptake with tissue markers of altered glucose metabolism and cellular proliferation, and to compare 18F-FDG PET scanning to standard imaging modalities in order to determine whether FDG-PET 1) may positively impact clinical management of the patient with hepatic colorectal metastases, 2) may potentially be useful for monitoring treatment responses for palliative treatments, and 3) may be a useful non-invasive predictor of prognosis.
Funding Period: 1999-04-02 - 2004-01-30
more information: NIH RePORT

Top Publications

  1. ncbi Hyperthermia potentiates oncolytic herpes viral killing of pancreatic cancer through a heat shock protein pathway
    David P Eisenberg
    Division of Surgical Oncology, Hartford Hospital, Hartford, CT, USA
    Surgery 148:325-34. 2010
  2. ncbi Kinetics of liver volume changes in the first year after portal vein embolization
    Danton CorrĂȘa
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Arch Surg 145:351-4; discussion 354-5. 2010
  3. ncbi Employing tumor hypoxia for oncolytic therapy in breast cancer
    Yun Shin Chun
    Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Mammary Gland Biol Neoplasia 10:311-8. 2005
  4. ncbi Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Thorac Cardiovasc Surg 132:1179-88. 2006
  5. ncbi Radiation-induced cellular DNA damage repair response enhances viral gene therapy efficacy in the treatment of malignant pleural mesothelioma
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Ann Surg Oncol 14:258-69. 2007
  6. ncbi Recent advancements in diagnosis and treatment of metastatic colorectal cancer to the liver
    Katherine T Morris
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Surg Oncol 15:129-34. 2006
  7. ncbi Adenoviral vector expressing hepatocyte growth factor promotes liver regeneration by preoperative injection: the advantages of performing selective injection to the remnant lobe
    Masaki Ueno
    Second Department of Surgery, Wakayama Medical University, School of Medicine, Japan
    Surgery 141:511-9. 2007
  8. pmc Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas
    Sandeep Malhotra
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Surgery 141:520-9. 2007
  9. ncbi 18F-FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases
    Christopher C Riedl
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Nucl Med 48:771-5. 2007
  10. ncbi A nomogram for predicting disease-specific survival after hepatic resection for metastatic colorectal cancer
    Michael W Kattan
    Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
    Ann Surg 247:282-7. 2008

Detail Information

Publications27

  1. ncbi Hyperthermia potentiates oncolytic herpes viral killing of pancreatic cancer through a heat shock protein pathway
    David P Eisenberg
    Division of Surgical Oncology, Hartford Hospital, Hartford, CT, USA
    Surgery 148:325-34. 2010
    ..This study investigates a novel therapeutic regimen, combining the effects of NV1066 (a recombinant HSV-1) and hyperthermia in the treatment of pancreatic cancer...
  2. ncbi Kinetics of liver volume changes in the first year after portal vein embolization
    Danton CorrĂȘa
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Arch Surg 145:351-4; discussion 354-5. 2010
    ..To determine the time course of liver hypertrophy after portal vein embolization (PVE)...
  3. ncbi Employing tumor hypoxia for oncolytic therapy in breast cancer
    Yun Shin Chun
    Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Mammary Gland Biol Neoplasia 10:311-8. 2005
    ..Such a targeted approach will increase efficacy in the therapy of hypoxic tumors while achieving a reduction in total dose of viral therapy...
  4. ncbi Intraoperative localization of lymph node metastases with a replication-competent herpes simplex virus
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Thorac Cardiovasc Surg 132:1179-88. 2006
    ..This study investigates the potential to identify lymph node metastases intraoperatively by using herpes-guided cancer cell-specific expression of green fluorescent protein...
  5. ncbi Radiation-induced cellular DNA damage repair response enhances viral gene therapy efficacy in the treatment of malignant pleural mesothelioma
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Ann Surg Oncol 14:258-69. 2007
    ..Such stress response is beneficial for oncolytic viral therapy. We hypothesized that a combination of RT and NV1066, an oncolytic herpes virus, might exert an additive or synergistic effect in the treatment of MPM...
  6. ncbi Recent advancements in diagnosis and treatment of metastatic colorectal cancer to the liver
    Katherine T Morris
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Surg Oncol 15:129-34. 2006
  7. ncbi Adenoviral vector expressing hepatocyte growth factor promotes liver regeneration by preoperative injection: the advantages of performing selective injection to the remnant lobe
    Masaki Ueno
    Second Department of Surgery, Wakayama Medical University, School of Medicine, Japan
    Surgery 141:511-9. 2007
    ..The aim of this study is to evaluate the benefits of the selective and preoperative injection of AdHGF to the remnant lobes to regenerate the liver...
  8. pmc Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas
    Sandeep Malhotra
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Surgery 141:520-9. 2007
    ..The purpose of this study was to compare NV1034 to NV1023, the parent HSV mutants lacking GM-CSF, to determine if such combined oncolytic and immunotherapy using a single vector has advantages over oncolytic therapy alone...
  9. ncbi 18F-FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases
    Christopher C Riedl
    Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Nucl Med 48:771-5. 2007
    ..The aim of the current study was to determine whether this biologic scan would correlate with other cellular characteristics and the clinical behavior of tumors...
  10. ncbi A nomogram for predicting disease-specific survival after hepatic resection for metastatic colorectal cancer
    Michael W Kattan
    Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
    Ann Surg 247:282-7. 2008
    ..By using a nomogram we are trying to improve on the current practice of using prognostic scores for evaluating risks of therapeutic failure...
  11. ncbi Roux-en-Y reconstruction after pancreaticoduodenectomy
    Stephen R Grobmyer
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Arch Surg 143:1184-8. 2008
    ..Roux-en-Y reconstruction (RYR) is associated with a reduction in morbidity and mortality associated with pancreatic anastomotic failure after pancreaticoduodenectomy compared with conventional loop reconstruction (CLR)...
  12. pmc Regression of human pancreatic tumor xenografts in mice after a single systemic injection of recombinant vaccinia virus GLV-1h68
    Yong A Yu
    Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, CA 92109, USA
    Mol Cancer Ther 8:141-51. 2009
    ..In conclusion, the GLV-1h68 strain showed outstanding therapeutic effects and a documented safety profile in mice, with great promise for future clinical development...
  13. ncbi Advances in oncolytic viral therapy
    Yanghee Woo
    Memorial Sloan Kettering Cancer Center, Department of Surgery, 1275 York Avenue, New York, NY 10021, USA
    Curr Opin Investig Drugs 7:549-59. 2006
    ....
  14. pmc Real-time intraoperative detection of breast cancer axillary lymph node metastases using a green fluorescent protein-expressing herpes virus
    David P Eisenberg
    Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Ann Surg 243:824-30; discussion 830-2. 2006
    ..To investigate the use of a green fluorescent protein (GFP)-expressing oncolytic herpes virus to enable real-time intraoperative detection of breast cancer lymph node metastases...
  15. pmc Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer
    Brendon M Stiles
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Int J Oncol 28:1429-39. 2006
    ..These data provide the mechanistic basis for the use of oncolytic HSV-1 in patients with hormone receptor-positive breast cancer, particularly if the disease progresses with conventional therapies...
  16. pmc Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer
    B M Stiles
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cancer Gene Ther 13:53-64. 2006
    ....
  17. pmc Radiation therapy potentiates effective oncolytic viral therapy in the treatment of lung cancer
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Ann Thorac Surg 80:409-16; discussion 416-7. 2005
    ..We hypothesized that radiation therapy may potentiate efficacy of oncolytic viral therapy by upregulating GADD34 and promoting viral replication...
  18. ncbi Citation characteristics of basic science research publications in general surgical journals
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Surg Res 128:168-73. 2005
    ..The purpose of this study is to characterize the BSR publications in GS journals and to analyze their citation frequencies...
  19. ncbi Herpes simplex virus amplicon delivery of a hypoxia-inducible soluble vascular endothelial growth factor receptor (sFlk-1) inhibits angiogenesis and tumor growth in pancreatic adenocarcinoma
    Maura Reinblatt
    Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Ann Surg Oncol 12:1025-36. 2005
    ..We attempted to attenuate angiogenesis and inhibit pancreatic tumor growth through HSV amplicon-mediated expression of sFlk-1 under hypoxic control...
  20. pmc 5-fluorouracil and gemcitabine potentiate the efficacy of oncolytic herpes viral gene therapy in the treatment of pancreatic cancer
    David P Eisenberg
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York 10021, USA
    J Gastrointest Surg 9:1068-77; discussion 1077-9. 2005
    ..These data provide the cellular basis for the clinical investigation of combined oncolytic herpes virus therapy and chemotherapy in the treatment of pancreatic cancer...
  21. pmc Virally directed fluorescent imaging improves diagnostic sensitivity in the detection of minimal residual disease after potentially curative cytoreductive surgery
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York 10021, USA
    J Gastrointest Surg 9:1138-46; discussion 1146-7. 2005
    ..Virally directed fluorescent imaging, a novel molecular imaging technology, can be used for real-time visualization of minimal residual disease after cytoreductive surgery and can improve the completeness of cure-intended resection...
  22. pmc Cisplatin-induced GADD34 upregulation potentiates oncolytic viral therapy in the treatment of malignant pleural mesothelioma
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Biol Ther 5:48-53. 2006
    ..We hypothesized that cisplatin upregulates GADD34 expression, which enhances NV1066 replication and oncolysis...
  23. ncbi Recent chemotherapy reduces the sensitivity of [18F]fluorodeoxyglucose positron emission tomography in the detection of colorectal metastases
    Timothy Akhurst
    Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Clin Oncol 23:8713-6. 2005
    ..Because cytotoxic chemotherapy may decrease the cellular metabolic activity of tumor, we assessed the effects of chemotherapy on PET imaging...
  24. pmc Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging
    P S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Surg Endosc 20:628-35. 2006
    ..We sought to determine the feasibility of GFP-guided imaging technology in the intraoperative detection of small tumor nodules...
  25. pmc Real-time diagnostic imaging of tumors and metastases by use of a replication-competent herpes vector to facilitate minimally invasive oncological surgery
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    FASEB J 20:726-8. 2006
    ..These studies form the basis for real-time, intraoperative diagnostic imaging of tumor and metastases by minimally invasive endoscopic technology...
  26. pmc Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses
    Prasad S Adusumilli
    Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Gene Med 8:603-15. 2006
    ..The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy...
  27. pmc Herpes simplex virus based gene therapy enhances the efficacy of mitomycin C for the treatment of human bladder transitional cell carcinoma
    Michael Mullerad
    Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Urol 174:741-6. 2005
    ....