Radioguided Surgery (eBook)

*Anatomy and physiology of lymphatic circulation as it relates to metastatic spread of solid cancers *The role of lymph node staging for clinical decision making in patients with solid cancers *Techniques to identify sentinel lymph nodes in patients with: Breast cancer, Melanoma, Penile carcinoma, Head and neck cancer, Ovarian cancer, Vulvar cancer, Endometrial cancer, Cancers of the gastrointestinal tract and pancreas, Neuroendocrine tumors, Prostate cancer, Non-small cell lung cancer *Histopathology of sentinel lymph nodes: Imprint cytology in sentinel lymph node biopsy, Conventional histology and immunohistochemistry, Molecular biology techniques for sentinel lymph nodes *Non-sentinel-node applications of radioguided surgery: Breast cancer, Parathyroid tumors, Neuroendocrine tumors, Solitary lesions in the lung, Thyroid cancer, Present role of radioimmunoguided surgery *The perspective of the nuclear medicine physician, the surgeon, and the pathologist *Radiopharmaceuticals for radioguided surgery *Instrumentation: Physical performance parameters of intraoperative probes, and other technical issues of radioguided surgery, Imaging probes and positron-sensitive probes *Radiation protection issues in radioguided surgery *Training and credentialing for radioguided surgery

"21 Where It All Began: The Heritage of Radioimmunoguided Surgery (p. 221)

Fausto Badellino, Mario Roselli, Marzio Perri, Fiorella Guadagni, and Giuliano Mariani

Nowadays some monoclonal antibodies are available that, as magic bullets, are able to reach malignant cells growing in the body and, if carrying appropriate antineoplastic agents, can provide their destruction while sparing normal healthy tissues.
—Renato Dulbecco, Nobel Laureate for Physiology and Medicine, 1975

In the mid-1970s, crucial advances in immunology led to widespread fascination with the development of radiolabeled antibodies for immunoscintigraphy of primary or secondary tumors.

The availability of these radiolabeled tumor-seeking agents constituted the ? rst step toward radioimmunoguided surgery, as pioneered by Martin et al. (1,2) in patients with colorectal cancer. This chapter provides an overview of the evolution of the radioimmunoguided surgery system, explains its main technical aspects, and outlines its clinical applications. Intraoperative detection of cancer by means of tumorspeci ? c radiolabeled antibodies evolved from seminal experiments in the early 1970s, which demonstrated the ability of radiolabeled immunoglobulin G against carcinoembryonic antigen (CEA) to localize human GW-39 tumors implanted in hamsters (3,4).

After Kohler and Milstein described a method of preparing large numbers of speci? c monoclonal antibodies (MABs) in 1975 (5), the technique was optimized and, in the beginning of the 1980s, the B72.3 MAB was generated by using membrane- enriched extracts of human metastatic mammary carcinoma lesions (6). The reactivity of this MAB with formalin-? xed, paraf? n-embedded tissue sections of human colon adenocarcinomas and adenomas was especially promising (7).

The tumor-associated glycoprotein recognized by the B72.3 MAB (TAG-72) is a member of the mucin family. Shortly thereafter, some research groups began exploring the diagnostic potential of radioimmunodetection, a new technique that combined the administration of radiolabeled antibodies with external imaging to identify clinically occult tumors (8,9). Other groups examined the potential of intraoperative radioactivity counting to detect the uptake of radiolabeled MABs by malignant cells.

These latter experiences led to the development of a dedicated handheld gamma-detecting probe for intraoperative use, which improved the sensitivity of external radioimmunodetection (10,11). The ? rst prototypes were tested in 1983–1984 by Martin’s group (1,12) at the Comprehensive Cancer Center of the Ohio State University in Columbus. In a pilot clinical study with radiolabeled MAB B72.3 in patients with recurrent colorectal cancer, intraoperative use of the gamma probe localized the tumor-bound antibody in 82% of the patients and detected a clinically occult tumor in 8 of 31 patients (13).

In the following years, the same investigators employed MAB B72.3 in 66 patients with different malignant tumors (2). The gamma probe identi? ed positive counts in 5 of 6 patients with primary colon cancer (83.3%), in 31 of 39 patients with recurrent colon cancer (79.5%), in 4 of 5 patients with gastric cancer (80%), in 3 of 8 patients with breast cancer (37.5%), and in 4 of 8 patients with ovarian cancer (50%). Overall, radioimmunoguided surgery identi? ed tumor lesions in 47 patients (71.2%), was equivocal-positive in 6 patients (9.1%), and failed to detect an occult tumor in 13 (19.7%).

By placing the gamma probe directly over the areas of interest, radioimmunoguided surgery had the advantage of minimizing the in? uence of the inverse-square law on the counting rate for any given radioactive source. Radioimmunoguided surgery allowed accurate clinical assessment of the surgical area before and after treatment, and identi? ed residual disease in a signi? cant number of cases. In the early 1990s, the development of second-generation MABs speci? cally for colon cancer led to further improvements in radioimmunoguided surgery for patients with this malignancy. These MABs were characterized by in-vitro immunological assays (14), and 6 of them (CC11, CC30, CC46, CC49, CC83, and CC92) were chosen for in-vivo tumor targeting in a murine model of"