Computed tomography injection of technetium 99m macroaggregated albumin—an underutilized lung nodule localization strategy in pediatric patients

Accurate localization and biopsy of pulmonary nodules in pediatric patients is a crucial step in the workup, staging, and treatment of malignancy. Lung is the most common solid organ for tumor metastasis in the pediatric population. Accurate identification of nodules which may be too small to visualize by a thoracoscopic approach, too deep in the parenchyma, or simply too small or too soft to palpate present a challenge. Many localization techniques are employed to facilitate a minimally invasive approach or open thoracotomy approach to surgical biopsy or provide complete surgical resection with preservation of native, unaffected lung tissue. We aim to briefly review the commonly used localization strategies and would suggest consideration for wider adoption of computed tomography (CT) guided radionucleotide technetium 99m macroaggregated albumin injection to localize possible lung metastases in pediatric age patients.

Over the years, different lung localization strategies have been employed to identify potential metastases in pediatric oncology patients. These include using preoperative intravenous infusion of indocyanine green (ICG) to identify tumors that metabolize ICG allowing use of intraoperative near infrared fluorescence to localize them in the operating room. Other approaches depend upon direct injection of ICG or methylene blue or placement of wires (similar to breast cancer localization) into lesions of interest.

Recent studies have looked at the efficacy of whether intravenous infusion of ICG within 24–48 hours preoperatively with the use of near infrared fluorescent enabled thoracoscopy to identify uptake of ICG by the nodule of interest. This method is advantageous as it avoids an invasive preoperative procedure and the associated complications, and decreased anesthesia time for a separate invasive procedure. Finally, this can be considered as an option for infusion to be administered on an outpatient basis. Interestingly, this technique also demonstrated impressive sensitivity to detect nodules not detected on the imaging as 13 of 79 examined nodules were identified by fluorescence alone with ICG (1). However, there were major drawbacks to the use of ICG as it did not have ubiquitous uptake in many metastatic tumors. Tumors that did not uptake ICG include inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, and papillary thyroid carcinoma. In this study, the protocol was notably discontinued prematurely due to sensitivity of 75% which was below the target of 90%. A meta-analysis did identify overall intravenous route of ICG to have a success rate of 88% (2).

An alternative technique not described in the pediatric literature involves injection of ICG directly into lung nodules using CT guidance. Again, with near infrared thoracoscopy, the targeted nodules fluoresce and visually are identified for targeted biopsy (3). This technique is advantageous with the increased utilization of robot assisted thoracoscopy enabled with near infrared capabilities of this modality. The authors identify the fluorescent color change is helpful to distinguish from surrounding anthracosis or vessels. One of the primary drawbacks of this technique involves exposure to complications of invasive intrapulmonary procedures. The authors did not test this technique with lesions greater than 2 cm below the parenchymal surface. Timing is critical as the fluorescent dye tends to diffuse in a matter of minutes from point of injection, a major drawback of dye injection localization strategies. One means of reducing time from injection to biopsy would involve utilization of a hybrid operating room for CT-guided procedures followed by immediate biopsy. Considering the diagnostic yield of ICG, a meta-analysis identified success rate for CT-guided localization to be 94.8% (2).

Another well-reported dye infusion procedure involves CT-guided methylene blue injection into tumor with subsequent identification of the blue-tattooing in the lung parenchyma on standard thoracoscopy. The cost of the agent is affordable, and availability is wide, which is advantageous. In a collaborative study of 15 North American pediatric institutions, isolated methylene blue dye localization is the second most reported localization technique utilized in 25% of studied cases and in combination with wire localization in 28% (4). Again, the common difficulty with this technique is the rapid diffusion of the injected dye and this is problematic when attempting to locate small lesions with high accuracy. One adaptation employed involves mixing the dye with autologous blood to slow the diffusion process. This is a historically successful method, with reported diagnostic yield to be 99.5% (5). There is also a rare complication of anaphylaxis associated with methylene blue.

Wire localization is another method successfully used in localizing pulmonary lesions. This is adapted from breast lesion localization in which a wire is percutaneously placed by CT guidance into the lesion of interest to be followed at time of surgical biopsy or resection. With respect to pediatric patients, used in isolation this technique was reported to be used in 14% of patients and combined with methylene blue comprised 28% of patients undergoing lung resection in the collaborative study of pediatric cancer patients (4). The surgeon will follow the course of the wire into the parenchyma and is helpful to identify lesions located deeper. This has also been successfully used even in isolation, with diagnostic yield greater than 93% (6). One of the complications unique to wire localization is wire dislodgement or migration which can occur around 2.5% of the time (7,8).

Coil localization is another effective strategy which uses similar procedure for wire placement under CT guidance for implantation of a micro coil into lung parenchyma with good success reported for localization of small pulmonary nodules achieving 93–98% (9). Also, like wire localization, micro coils are not immune to dislodgement or migration, with a devastating complication of embolization to cause acute coronary syndrome (10). Coils require the use of intraoperative fluoroscopy exposing the patient to additional radiation.

CT guided radio tracer injection with technetium-99m macroaggregated albumin in lung lesions is an excellent technique not commonly utilized in the pediatric population. This technique requires preoperative CT-guided injection of the tracer into the lung lesion the morning of the operation. Post-injection scintigraphy is then obtained to ensure intraparenchymal injection. If desired a single photon emission computed tomography (SPECT) scan can be obtained for further anatomic delineation though is not necessary. Technetium 99m is stable for 6 hours and is a commonly used radionucleotide isotope applied in many other nuclear scintigraphy procedures and is widely available. Technetium 99m combined with the large molecule of macroaggregated albumin is used for lung perfusion scintigraphy. The large protein prevents rapid diffusion of radiotracer into the parenchyma or lymphatics, obviating the issues faced by direct injection with dye marking agents.

Following injection, the patient is then taken to the operating room and thoracoscopy or thoracotomy is performed. Prior to making incision, the gamma probe can be placed on the skin to identify the area of the lesion to allow for optimal incision planning intraoperatively, the gamma probe (for example Daniel Lung Probe, Dilon Diagnostics, Newport News, VA, USA) is introduced into the chest via thoracotomy or 12 mm thoracoscopy incision and used by the operative surgeon which allows rapid direct localization of lung lesions based on the gamma counts. The gamma probe localizes lesions to within 2–3 mm of the injection site. Gamma counting can also be used when the specimen is removed to ensure the labeled lesion is included in the specimen. Masses that do not take up ICG, that are soft and cannot be palpated and are deep to the pleura can also be identified and resected by this technique. Radiotracer localization is also advantageous compared to wires or coils in that the tracer does not become dislodged, displaced or embolize. The success of this technique in pediatric patients is 96% with non-palpable lesions as small as 2 mm identified and resected (11). However, this technique exposes the patient to a small amount of additional radiation for the CT localization procedure and the post-injection scintigraphy (9). Additionally, hospitals who use this technique require support of nuclear medicine services and must have access to a gamma probe which can be used thoracoscopically.

There are many factors to consider when selecting the optimal localization strategy. The CT-guided procedures all carry a similar risk profile which may not carry as much weight in the decision. Indeed, these all require collaboration between interventional radiologists and surgeons and their respective experience of these specialists will play a significant role in decision. Comprehensive randomized controlled trials are lacking comparing all the above-described techniques.

Conclusions

Though all the localization techniques have reportedly been employed for successful nodule localization, we would strongly suggest wider utilization of CT guided technetium 99m macroaggregated albumin radio tracer injection to localize lung metastases in pediatric patients. It has the benefit of precise localization and substantial time from injection to time of diffusion without risk of dislodgement or displacement. The gamma probe is simple to use and has excellent diagnostic yield. There is also important versatility to be pointed out as this technique has also been successfully applied for the localization of lymph nodes in dense lymphatic beds for precise lymph node localization using the same technique for injection as with lung nodule localization (12).

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article has undergone external peer review.

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Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-24-2/coif). The authors have no conflicts of interest to declare.

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