The Role of Technetium-99m in Sentinel Lymph Node Detection for Gynecological Cancers

 Introduction

Accurate cancer staging is one of the most crucial steps in developing effective treatment strategies for patients with gynecologic malignancies. The identification of sentinel lymph nodes (SLNs) — the first lymph nodes to receive drainage from a primary tumor  plays a pivotal role in determining whether cancer has begun to spread.

Among the various methods developed for SLN mapping, Technetium-99m (Tc-99m) has emerged as the gold standard radiotracer for lymphoscintigraphy, thanks to its favorable imaging characteristics, safety, and reproducibility.

What Is Technetium-99m?

Technetium-99m is a metastable isotope widely used in nuclear medicine because of its short half-life (around 6 hours) and ideal gamma emission (140 keV). When bound to nanocolloids or human serum albumin, it travels through lymphatic channels and accumulates in lymph nodes, making them visible under gamma camera or SPECT/CT imaging.

Its use in sentinel node detection has significantly improved preoperative mapping and intraoperative navigation using handheld gamma probes, allowing for precise and minimally invasive surgeries.

 Clinical Applications in Gynecologic Oncology

1. Vulvar Cancer

SLN mapping using Tc-99m combined with blue dye is now recommended as the standard of care for early-stage vulvar cancer (tumor size ≤4 cm).
The landmark GROINSS-V study demonstrated that patients with negative sentinel nodes can safely avoid complete lymphadenectomy, drastically reducing complications such as lymphedema and wound infections.

2. Cervical Cancer

In cervical cancer, SLN detection rates reach up to 96% when Tc-99m is combined with a blue dye or indocyanine green.
The SENTICOL trials confirmed that Tc-99m lymphoscintigraphy not only identifies sentinel nodes accurately but also detects atypical drainage pathways (e.g., para-aortic or sacral nodes), improving surgical precision.
SPECT/CT enhances the accuracy of mapping from 85% to nearly 99%.

3. Endometrial Cancer

SLN biopsy guided by Tc-99m reduces the need for full lymphadenectomy in low- and intermediate-risk endometrial cancers.
Detection sensitivity is about 90%, with a false-negative rate below 5%.
The one-day injection protocol provides superior visualization of para-aortic drainage, while SPECT/CT improves anatomic localization.

4. Ovarian and Vaginal Cancers

Although still under clinical evaluation, early trials such as MELISA show that Tc-99m combined with fluorescent tracers can detect sentinel nodes in up to 90% of early-stage ovarian cancers, offering a safer alternative to extensive lymph node dissection.

 Ultrastaging: Detecting Micrometastases

Traditional pathology may overlook micrometastases (tumor clusters <2 mm) or isolated tumor cells (ITCs).
With Tc-99m-guided biopsy, ultrastaging techniques — including deeper tissue sectioning and immunohistochemistry — enable earlier detection of these microscopic lesions.

This approach not only refines staging accuracy but also improves survival prediction, as micrometastases are associated with up to a 20% decrease in 8-year survival rates.

Clinical Impact

The integration of Tc-99m lymphoscintigraphy into gynecologic oncology has transformed surgical management by:

• Providing high diagnostic accuracy

• Enabling minimally invasive procedures

• Reducing postoperative complications

• Allowing for real-time intraoperative guidance

• Supporting individualized cancer staging

 Future Perspectives

Emerging technologies aim to further enhance SLN detection:

• Hybrid tracers (Tc-99m + fluorescent dyes) enable simultaneous radiologic and visual identification.

• Artificial intelligence is being developed to improve SPECT/CT image interpretation.

• Standardization of ultrastaging protocols is underway to ensure global consistency in SLN pathology evaluation.

 Conclusion

Technetium-99m remains the cornerstone radiotracer for sentinel lymph node mapping in gynecologic cancers. Its superior imaging quality, safety profile, and compatibility with advanced imaging modalities such as SPECT/CT make it indispensable in modern oncologic surgery.

As clinical trials continue to refine protocols and validate new tracers, Tc-99m-guided lymphoscintigraphy will remain at the heart of personalized, precision-based cancer care.

Reference