# Pediatric Oncologic Nuclear Medicine

## Introduction

Nuclear medicine plays an essential role in the diagnosis, staging, treatment monitoring, and surveillance of pediatric malignancies. Key modalities include F-18 FDG PET/CT, I-123 MIBG scintigraphy, and Tc-99m MDP bone scanning. Unique considerations in pediatric oncologic imaging include radiation dose optimization, physiologic variants in growing children, and disease-specific imaging algorithms.

## F-18 FDG PET/CT in Pediatric Oncology

### General Principles

F-18 fluorodeoxyglucose (FDG) is the most widely used PET tracer in pediatric oncology. The administered activity is 3.7 to 5.2 MBq/kg with a minimum of 26 MBq per consensus guidelines. Patients must fast for 4 to 6 hours, and blood glucose should be below 200 mg/dL. A low-dose CT protocol is used for attenuation correction and anatomic localization.

### Pediatric-Specific Physiologic Variants

Several physiologic patterns of FDG uptake are unique to or more prominent in pediatric patients. Thymic uptake is normal and prominent in young children and may increase after chemotherapy, a phenomenon known as thymic rebound. Brown fat activation is common in children, especially in the neck and supraclavicular regions, and can mimic lymphadenopathy. Growth plate uptake represents normal physiologic FDG activity at open physes and should not be mistaken for metastatic disease. Tonsillar and adenoidal uptake reflects benign reactive lymphoid tissue. Diffuse bone marrow uptake occurs after chemotherapy or with G-CSF administration.

### Lymphoma

Hodgkin lymphoma is FDG-avid in virtually all cases, and PET/CT is the standard modality for staging and response assessment. The Deauville criteria, a 5-point scale, are used for both interim and end-of-therapy response evaluation. Most subtypes of non-Hodgkin lymphoma are FDG-avid, with Burkitt lymphoma being highly metabolically active. PET-adapted therapy protocols allow reduction of treatment intensity for early responders, sparing patients from unnecessary toxicity.

### Sarcomas

Ewing sarcoma is uniformly FDG-avid, and PET/CT is superior to conventional imaging for detecting metastatic disease. Osteosarcoma demonstrates high FDG uptake, and a reduction in SUV after chemotherapy correlates with histologic necrosis, serving as a prognostic indicator. Rhabdomyosarcoma has variable FDG avidity depending on the histologic subtype. PET/CT is useful for detecting osseous and soft tissue metastases that are missed by conventional imaging.

## I-123 MIBG Scintigraphy

### Neuroblastoma

I-123 metaiodobenzylguanidine (MIBG) is the primary imaging agent for neuroblastoma. Approximately 90% of neuroblastomas are MIBG-avid. The Curie scoring system and SIOPEN scoring system are used to quantify disease burden semi-quantitatively. Mandatory thyroid blockade with potassium iodide or Lugol solution is required prior to administration.

### Protocol

The administered activity is 5.2 MBq/kg with a minimum of 37 MBq. Imaging is performed at 24 hours post-injection, with optional 4-hour early images. Whole-body planar imaging is combined with spot views and SPECT/CT of areas of interest. Medications that must be withheld include sympathomimetics, tricyclic antidepressants, and labetalol.

### Response Assessment

MIBG response criteria are incorporated into the International Neuroblastoma Response Criteria (INRC). Semi-quantitative scoring correlates with prognosis and guides decisions about therapy escalation. Approximately 10% of neuroblastomas are MIBG-non-avid, representing a source of false negatives. FDG PET/CT should be considered as an alternative imaging modality in these cases. Post-therapy I-131 MIBG imaging is used for treatment monitoring in therapeutic applications.

### I-131 MIBG Therapy

High-dose I-131 MIBG therapy is used for relapsed or refractory neuroblastoma. It requires radiation isolation, and stem cell support may be needed for myeloablative doses. Azedra (iobenguane I-131) is FDA-approved for pheochromocytoma and paraganglioma in patients aged 12 and older.

## Bone Scintigraphy in Pediatric Oncology

### Tc-99m MDP Bone Scan

Tc-99m MDP bone scanning is useful for osteosarcoma, Ewing sarcoma, and other primary bone tumors. It detects skeletal metastases with high sensitivity. Growth plate activity is normal and should not be confused with pathology. Bone scanning is complementary to MIBG in neuroblastoma, detecting cortical bone metastases that may be less conspicuous on MIBG.

### Limitations

Bone scanning has lower specificity than PET/CT for osseous metastases. It cannot distinguish treatment response as effectively as FDG PET. It is being increasingly supplanted by PET/CT in many pediatric oncology protocols.

| Pediatric Malignancy | Primary Nuclear Medicine Modality | Key Imaging Agent | Response Criteria |
|---|---|---|---|
| Hodgkin lymphoma | FDG PET/CT | F-18 FDG | Deauville 5-point scale |
| Non-Hodgkin lymphoma | FDG PET/CT | F-18 FDG | Deauville 5-point scale |
| Neuroblastoma | MIBG scintigraphy | I-123 MIBG | Curie/SIOPEN scoring |
| Ewing sarcoma | FDG PET/CT | F-18 FDG | SUV reduction post-chemo |
| Osteosarcoma | FDG PET/CT + bone scan | F-18 FDG / Tc-99m MDP | SUV correlates with necrosis |
| Rhabdomyosarcoma | FDG PET/CT | F-18 FDG | Variable avidity by subtype |
| Wilms tumor | Limited role | — | Conventional imaging preferred |

## Other Radiopharmaceuticals in Pediatric Oncology

Ga-68 DOTATATE PET/CT has an emerging role in pediatric neuroendocrine tumors and neuroblastoma. F-18 DOPA PET serves as an alternative for MIBG-non-avid neuroblastoma. Tc-99m sestamibi has limited use in pediatric brain tumors. In-111 pentetreotide has been largely replaced by Ga-68 DOTATATE for somatostatin receptor imaging.

## Radiation Safety Considerations

Image Gently principles with weight-based dosing should always be applied. Low-dose CT protocols are used for hybrid imaging. Repeat studies should be minimized through careful protocol selection. Cumulative radiation exposure from serial imaging over the treatment course should be considered. Cumulative effective dose should be documented in the medical record when possible.

## Clinical Pearls

Thymic rebound, brown fat activation, and growth plate uptake are common physiologic variants on pediatric FDG PET/CT that should not be mistaken for disease.

I-123 MIBG is the primary staging and response assessment tool for neuroblastoma, with mandatory thyroid blockade before administration.

The Deauville 5-point scale is the standard for interim and end-of-therapy response assessment in pediatric Hodgkin lymphoma.

Approximately 10% of neuroblastomas are MIBG-non-avid. FDG PET/CT or Ga-68 DOTATATE PET/CT should be considered as alternatives in these cases.

## References

1. Sharp SE, et al. "Pediatric FDG PET/CT: Physiologic Uptake, Normal Variants, and Benign Conditions." *Radiographics*. 2017;37(5):1529-1546.
2. Parisi MT, et al. "I-123 MIBG Scintigraphy in Neuroblastoma: An Update on Recommended Procedures and Interpretation." *Pediatr Radiol*. 2016;46(9):1237-1250.
3. Cheson BD, et al. "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification." *J Clin Oncol*. 2014;32(27):3059-3068.
4. Gelfand MJ, et al. "Pediatric Radiopharmaceutical Administered Doses: 2010 North American Consensus Guidelines." *J Nucl Med*. 2011;52(2):318-322.