Abstract
Sentinel lymph node (SLN) identification with preoperative image guidance may improve pathological staging of prostate cancer by identifying nodes outside the standard template of dissection. Four anesthetized male dogs received an intra-prostatic injection of Ga-68-labeled tilmanocept. Every 20 min the pelvic lymph nodes were imaged using PET/CT fusion imaging. At 90 min post-injection a prostatectomy and extended lymphadenectomy were completed; ex vivo radioactivity was recorded for each node using a handheld gamma detector, and confirmed by calculation of percent-of-injected dose (%ID) via assay of Ga-68 radioactivity. SLNs were defined as containing >10 % of the maximum %ID. Preoperative PET/CT fusion imaging identified a mean of 4.25 lymph nodes per animal (range 3–7); the mean number of SLN per animal was 4.00 (range 2–6).Of the excised SLNs, 29 % were located in the standard external iliac and obturator distribution. The SLN %ID ranged from 0.07 to 2.40 % (mean 0.744 % ± 0.641 %); SLN ex vivo count rate ranged from 88 to 2,175 cpm (mean 896 ± 715 cpm); and the SLN standardize uptake values (SUVs) ranged from 13 to 237 (mean 79 ± 67).There was a high concordance of PET-CT imaging to SLN activity, with sensitivity of 93 %. In this feasibility study, pelvic SLNs attained SUVs within 60 min. PET/CT effectively identified SLNs with good anatomic specificity, and radioactivity by hand-held detection and scintillation counts demonstrated high concordance with preoperative imaging. Gallium-68-labaled tilmanocept was highly specific for sentinel nodes. Image-guided tumor resection and lymphadenectomy may become a promising future application in urologic oncology and warrants further investigation.
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Abbreviations
- CT:
-
Computed tomography
- DTPA:
-
Diethylenetriaminepentaacetic acid
- ePLND:
-
Extended pelvic lymph node dissection
- PLND:
-
Pelvic lymph node dissection
- PET:
-
Positron-emission tomography
- SLN:
-
Sentinel lymph node
- SUV:
-
Standardized uptake value
- %ID:
-
Percent injected dose
References
Mattei A, Fuechsel FG, Bhatta Dhar N, Warncke SH, Thalmann GN, Krause T, Studer UE (2008) The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol 53:118–125
Flocks RH, Culp D, Porto R (1959) Lymphatic spread from prostatic cancer. J Urol 81:194–196
Daneshmand S, Quek ML, Stein JP, Lieskovsky G, Cai J, Pinski J, Skinner EC, Skinner DG (2004) Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. J Urol 172:2252–2255
Cheng L, Zincke H, Blute ML, Bergstralh EJ, Scherer B, Bostwick DG (2001) Risk of prostate carcinoma death in patients with lymph node metastasis. Cancer 91:66–73
Joslyn SA, Konety BR (2006) Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 68:121–125
Bader P, Burkhard FC, Markwalder R, Studer UE (2002) Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol 168:514–518
Briganti A, Chun FK, Salonia A, Suardi N, Gallina A, Da Pozzo LF, Roscigno M, Zanni G, Valiquette L, Rigatti P, Montorsi F, Karakiewicz PI (2006) Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer. Eur Urol 50:1006–1013
Wawroschek F, Vogt H, Weckermann D, Wagner T, Harzmann R (1999) The sentinel lymph node concept in prostate cancer—first results of gamma probe-guided sentinel lymph node identification. Eur Urol 36:595–600
Wawroschek F, Vogt H, Weckermann D, Wagner T, Hamm M, Harzmann R (2001) Radioisotope guided pelvic lymph node dissection for prostate cancer. J Urol 166:1715–1719
Holl G, Dorn R, Wengenmair H, Weckermann D, Sciuk J (2009) Validation of sentinel lymph node dissection in prostate cancer: experience in more than 2,000 patients. Eur J Nucl Med Mol Imaging 36:1377–1382
Janetschek G, Jeschke S, Leeb K, Prammer P, Ziegerhofer J, Sega W (2007) Sentinel lymph node dissection for localized prostate cancer. Actas Urol Esp 31:686–692
Meinhardt W, Valdes Olmos RA, van der Poel HG, Bex A, Horenblas S (2008) Laparoscopic sentinel node dissection for prostate carcinoma: technical and anatomical observations. BJU Int 102:714–717
Winter A, Wawroschek F (2008) Lymphadenectomy in prostate cancer. Radio-guided lymph node mapping: an adequate staging method. Front Radiat Ther Oncol 41:58–67
Jeschke S, Beri A, Grull M, Ziegerhofer J, Prammer P, Leeb K, Sega W, Janetschek G (2008) Laparoscopic radioisotope-guided sentinel lymph node dissection in staging of prostate cancer. Eur Urol 53:126–133
Weckermann D, Dorn R, Holl G, Wagner T, Harzmann R (2007) Limitations of radioguided surgery in high-risk prostate cancer. Eur Urol 51:1549–1556; discussion 1556–1548
Takashima H, Egawa M, Imao T, Fukuda M, Yokoyama K, Namiki M (2004) Validity of sentinel lymph node concept for patients with prostate cancer. J Urol 171:2268–2271
Wawroschek F, Wengenmair H, Senekowitsch-Schmidtke R, Hamm M, Henke J, Schonberger T, Hauser A, Erhardt W, Harzmann R (2003) Prostate lymphoscintigraphy for sentinel lymph node identification in canines: reproducibility, uptake, and biokinetics depending on different injection startegies. Urol Res 31:152–158
Vera DR, Wallace AM, Hoh CK, Mattrey RF (2001) A synthetic macromolecule for sentinel node detection: [99mTc]DTPA-mannosyl-dextran. J Nucl Med 42:951–959
Hoh CK, Wallace AM, Vera DR (2003) Preclinical studies of [99mTc]DPTA-mannosyl-dextran. Nucl Med Biol 30:457–464
Albertini J, Lyman GH, Cox C, Yeatman T, Balducci L, Ku N, Shivers S, Berman C, Wells K, Rapaport D, Shons A, Horton J, Greenberg H, Nicosia S, Clark R, Cantor A, Reintgen DS (1996) Lymphatic mapping and sentinel node biopsy and lymphatic mapping of patients with breast cancer. JAMA 276:1818–1822
Wallace AM, Hoh CK, Vera DR, Darrah D, Schulteis G (2003) Lymphoseek: a molecular radiopharmceutical for sentinel node detection. Ann Surg Oncol 10:531–538
Wallace AM, Hoh CK, Ellner SJ, Darrah DD, Schulteis G, Vera DR (2007) Lymphoseek: a molecular imaging agent for melanoma sentinel lymph node mapping. Ann Surg Oncol 14:913–921
Wallace AM, Hoh CK, Limmer KK, Darrah DD, Schulteis G, Vera DR (2009) Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol. Nucl Med Biol 36:687–692
Silberstein JL, Derweesh IH, Kane CJ (2009) Lymph node dissection during robot-assisted radical prostatectomy: where do we stand? Prostate Cancer Prostatic Dis 12:227–232
Warncke SH, Mattei A, Fuechsel FG, Z’Brun S, Krause T, Studer UE (2007) Detection rate and operating time required for γ-probe-guided sentinel lymph node resection after injection of technetium-99m nanocolloid into the prostate with and without preoperative imaging. Eur Urol 52:126–133
van der Poel HG, Buckle T, Brouwer OR, Olmos RAV, van Leeuwen FWB (2011) Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodel tracer. Eur Urol 60:826–833
Salem CE, Wallace AM, Hoh CK, Vera DR (2006) A preclinical study of prostate sentinel node mapping with Lymphoseek. J Urol 175:744–748
Rossi EC, Ivanova A, Boggess JF (2011) Robotically assisted fluorescence-guided lymph node mapping with ICG for gynecologic malignancies: a feasibility study. Gynecol Oncol 124:78–82
Ting R, Aguilera TA, Crisp JL, Hall DJ, Eckelman WC, Vera DR, Tsien RY (2010) Fast 18F labeling of a near-infrared fluorophore enables positron emission tomography and optical imaging of sentinel lymph nodes. Bioconjug Chem 21:1811–1817
Emerson DA, Limmer KK, Hall DJ, Han S-Y, Eckelman WC, Kane CJ, Wallace AM, Vera DR (in press) A receptor-targeted fluorescent radiopharmaceutical for multi-reporter sentinel lymph node imaging. Radiology.
Acknowledgments
We thank Navidea Biopharmaceuticals for the tilmanocept. We thank Dr. Jonathon Sorger of Intuitive Surgical, Inc. for his review of the manuscript. This study was funded by National Cancer Institute grants P50 CA128346 and P30 CA023100.
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Stroup, S.P., Kane, C.J., Farchshchi-Heydari, S. et al. Preoperative sentinel lymph node mapping of the prostate using PET/CT fusion imaging and Ga-68-labeled tilmanocept in an animal model. Clin Exp Metastasis 29, 673–680 (2012). https://doi.org/10.1007/s10585-012-9498-9
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DOI: https://doi.org/10.1007/s10585-012-9498-9