Nuclear Medicine in Paediatric Oncology

1. The clinical problem

Childhood cancer is rare, biologically distinct from adult cancer and mostly curable. Survival now depends less on finding one more lesion than on giving each child just enough treatment: enough to cure, and no more, because survivors carry decades of risk from radiotherapy, anthracyclines and alkylating agents. Imaging therefore has three jobs: stage accurately enough to assign a risk group, show early whether treatment is working so that it can be reduced or intensified, and do so with the lowest radiation burden that answers the question.

Staging systems in force

INRGSS after Monclair 2009; LCH categories after Haupt 2013.

INRGSS in one paragraph

The INRG staging system is applied before any treatment. Locoregional tumours are L1 if none of the 20 image-defined risk factors (IDRFs) is present and L2 if one or more is present; IDRFs are features on CT or MRI, such as vessel encasement or extension into the spinal canal, that make upfront resection hazardous. Distant metastases define M, except MS: metastases confined to skin, liver and/or bone marrow in children younger than 18 months. In the INRG validation cohort, 5-year event-free survival was 90% for L1 and 78% for L2. MIBG and FDG decide between locoregional and metastatic disease; IDRFs themselves are radiological (CT or MRI) findings.

Where nuclear medicine changes management

• In paediatric HL, the ERA PET after two cycles decides whether a child receives radiotherapy.
• In neuroblastoma, MIBG (or FDG) establishes stage M and the post-induction score predicts outcome and triggers alternative strategies.
• In rhabdomyosarcoma and Ewing sarcoma, FDG PET/CT upstages occult nodal and bone disease that changes radiotherapy fields and risk group.
• In LCH, FDG shows extent (single- versus multisystem) and early response, which decides whether systemic therapy continues.

2. Tracers and why they work

Avidity by tumour

• Hodgkin lymphoma: the inflammatory background around Hodgkin and Reed–Sternberg cells is intensely avid; FDG is the reference functional test.
• Neuroblastoma: about 90% of tumours express NET, so MIBG is both the imaging test and the theranostic partner of ¹³¹I-MIBG. FDG shows more of the disease in stage 1–2 tumours and in the chest, abdomen and pelvis, whereas MIBG detects more skeletal and marrow disease in stage 4 (Sharp 2009: 44 of 85 stage 4 scans showed more sites on MIBG, 11 on FDG).
• Sarcomas: Ewing sarcoma and rhabdomyosarcoma are usually avid; FDG is less sensitive than CT for small lung nodules.
• LCH: active lesions are avid, and uptake falls before radiographs change, which is why FDG detects early response.
• Wilms tumour and hepatoblastoma: FDG is not part of standard staging. Wilms tumour appears among the less common indications with some evidence in the SNMMI/EANM guideline; in AFP-secreting hepatoblastoma, serum alpha-fetoprotein detected every relapse before imaging and was more specific than CT or PET/CT, so PET is reserved for localising a confirmed biochemical relapse.
• Germ cell tumours: FDG may help staging and recurrence (SNMMI/EANM lists them among less common indications); tumour markers and cross-sectional imaging lead.
• CNS tumours: amino-acid PET plays a more pertinent role than FDG because normal brain takes up little amino acid; interpret only with co-registered MRI (joint EANM/SIOPE/RAPNO/SNMMI guideline 2022).

3. Indications by clinical scenario

Paediatric guidelines are consensus documents without graded recommendations; the paediatric FDG guideline states that its recommendations represent expert opinion.

4. Evidence at a glance

5. Patient preparation and acquisition

What follows is what differs in children; otherwise standard FDG tumour practice applies (SNMMI/EANM paediatric FDG guideline 2021).

• Explain and prepare the family: verbal and written information; measure height and weight on the day; place the cannula in advance with anaesthetic cream; use distraction.
• Fasting: 4–6 h before FDG, continued during uptake; plain water is encouraged unless the child is nil by mouth for anaesthesia. Glucose-containing fluids and parenteral nutrition are replaced by saline. Glucose should be below 11.1 mmol/L (200 mg/dL), ideally below 7.8 mmol/L.
• Sedation and anaesthesia: avoid where possible. When general anaesthesia is needed, the child is nil by mouth for 6–8 h and anaesthesia is given just before acquisition, not during uptake. Feed-and-wrap (feeding, then swaddling so the infant sleeps) suits studies that need no fast; it cannot be used unchanged for FDG, which needs the 4–6 h fast, so plan infant FDG scans with the anaesthetic team.
• Brown fat: commoner in children. Keep the uptake room at least 24 °C with a warm blanket and avoid cold for 1–2 days. Premedication options: oral propranolol 1 mg/kg (usually 20–40 mg, maximum 40 mg) 60–90 min before injection in children over 10 years; intravenous fentanyl under sedation monitoring; or oral diazepam for anxious children.
• Quiet uptake: no talking, playing, chewing or crying if avoidable; a pacifier is allowed but causes oral muscle uptake, so note it.
• Bladder: void just before acquisition; change the nappy; catheterisation is not routine, but catheter or furosemide 0.5–1 mg/kg (maximum 40 mg) helps with pelvic tumours.
• Timing after treatment: at least 10 days after chemotherapy and 2–3 months after radiotherapy are suggested; allow 3 weeks after long-acting G-CSF.
• Coverage: vertex to toes for baseline lymphoma, sarcoma, neuroblastoma and LCH; skull base to mid-thigh can suffice for lymphoma follow-up without bone or limb disease.
• Uptake time: 60 min, and the same at every follow-up scan so that SUVs and qPET remain comparable.

Administered activity

The 2024 North American update advises the low end for smaller patients and lower activities on digital or long axial field-of-view systems.

Radiation dose and ALARA

• PET component: effective dose per MBq rises as children get smaller: 0.095 mSv/MBq at 1 year, 0.050 at 5 years and 0.025 at 15 years (SNMMI/EANM 2021); adult 0.019. Weight-based dosing therefore gives roughly similar totals across ages: about 3.9 mSv at 1 year, 4.3 at 5, 5.1 at 10 and 5.9 mSv at 15 years for mid-range activities.
• CT component: 1 to more than 10 mSv depending on purpose. Decide per region whether the CT is for attenuation correction only, attenuation plus localisation, or diagnosis; use weight- or size-based paediatric protocols with dose modulation, never age alone. Suggested CTDIvol for chest-abdomen-pelvis attenuation correction ranges from 0.6–0.8 mGy under 1 year to 1.6–2.6 mGy over 15 years (32 cm phantom).
• Follow-up scans: low-dose CT, adding a limited diagnostic CT only where needed.
• PET/MRI: in 18 children with solid tumours, whole-body PET/MRI detected 61 foci against 62 on PET/CT, with a 73% reduction in radiation dose.

6. Interpretation

Hodgkin lymphoma: Deauville and qPET

• Deauville score: the most intense residual site compared with mediastinal blood pool (score 2 if not above it) and liver (score 3 if above blood pool but not above liver; 4 if moderately above liver; 5 if markedly above liver or new lesions). Score 1 is no uptake above background.
• qPET: the peak SUV of the hottest residual lesion divided by the mean liver SUV, measured on the same scan. The published correspondences are qPET below 1.3 for Deauville 3 or less, 1.3–2 for Deauville 4 and above 2 for Deauville 5; above 3 identifies the small high-risk group (5-year EFS 47.6% in C1).
• Which threshold? EuroNet-PHL-C1 was designed in 2005 and counted residual uptake above blood pool (approximately Deauville 3 or more) as positive. EuroNet-PHL-C2 counts Deauville 1–3 with qPET below 1.3 as an adequate response. Other paediatric groups use different time points and thresholds, so name the protocol and threshold in the report.
• Liver as reference in children: keep uptake time and reconstruction identical to baseline, because qPET is a ratio that drifts with uptake time and noise.

Neuroblastoma: MIBG scores

• SIOPEN score: 12 skeletal segments, each scored 0–6 by extent (1–3 = number of discrete lesions; 4 = more than three lesions or diffuse involvement of less than 50%; 5 = diffuse 50–95%; 6 = whole segment); maximum 72. Intensity is not scored.
• Curie score: 9 skeletal segments plus soft tissue, each scored 0–3 (1 = one lesion; 2 = more than one; 3 = more than 50% of the segment); maximum 30.
• Relative score: the revised INRC use the post-treatment skeletal score divided by the baseline score; use the same method at every time point. The site's quick page on neuroblastoma shows a scored example.
• Pitfalls: physiological uptake in salivary glands, heart, liver, bowel and bladder, and faint normal adrenal uptake; MIBG-non-avid disease (read the FDG scan); treatment-related marrow change on FDG, which is less specific than MIBG for bone disease.

Sarcomas and LCH

• Rhabdomyosarcoma: report regional nodes by basin (the European guideline asks for loco-regional nodal assessment on MRI and PET), and distant bone, marrow and nodal disease. Small lung nodules are judged on chest CT, not PET.
• Ewing sarcoma and osteosarcoma: whole-body coverage is recommended; bone and marrow metastases outside the MRI field of the primary are the key additional findings, and the baseline SUV is the reference for response.
• LCH: lytic lesions with soft-tissue components are avid; also look at lymph nodes, thymus, liver, spleen, pituitary region and lungs. Lesions in the orbit, temporal bone, mastoid, sphenoid, zygoma, ethmoid, maxilla or skull base with intracranial extension are CNS-risk lesions and change management.

Normal variants and pitfalls in children

After Vali 2021, Franke 2023 and Otani 2021.

Wording the conclusion

• State the time point (staging, ERA after 2 cycles, late response), the protocol, the Deauville score and qPET of the hottest site, and whether the result meets the protocol's definition of adequate response.
• For neuroblastoma, give the scoring method, the absolute skeletal score and the relative score against baseline, and state MIBG avidity of the primary.
• Name physiological findings that could be misread (thymus, brown fat, physes) so the clinical team does not act on them.

7. Response assessment and follow-up

• Hodgkin lymphoma: the ERA after 2 cycles of OEPA decides radiotherapy. In C2 patients with an inadequate response, residual avid sites are reassessed at late response assessment and radiotherapy is restricted to sites that remain positive. Routine surveillance PET is not part of paediatric HL follow-up; beware of thymic rebound, which in C1 occurred in 133 of 291 patients as a growing thymic mass after chemotherapy.
• Neuroblastoma: revised INRC integrate the primary (RECIST longest diameter plus MIBG or FDG), soft-tissue and bone metastases, and marrow; MIBG or FDG replaces bone scintigraphy. Post-induction SIOPEN > 3 or Curie > 2 carries a poor prognosis; residual MIBG avidity after induction in MYCN-amplified tumours (Curie > 0) gave 3-year EFS of 11.8% against 49.6% without.
• Ewing sarcoma and osteosarcoma: SUV below 2.5 after neoadjuvant chemotherapy predicted better progression-free survival, but histological necrosis in the resected specimen remains the reference response measure.
• Rhabdomyosarcoma: response is measured on MRI of the primary; PET adds information on nodes and metastases, but the evidence for response decisions is limited.
• LCH: Histiocyte Society guidance reassesses after the first 6 weeks and recommends not changing the method of bone evaluation between assessments; if FDG is used at baseline, use it again to judge response. FDG detects falling activity before radiographs change.
• Late effects: the whole strategy of PET-adapted therapy is to reduce radiotherapy and alkylator exposure. Keep follow-up imaging to the minimum that changes management, prefer MRI or ultrasound where they answer the question, and communicate dose and benefit honestly with families (Image Gently principles).

8. Theranostics and emerging tracers

MIBG remains the scoring standard because SIOPEN and Curie scores were validated on it. A PET-based NET tracer will replace it only when scoring and response thresholds have been revalidated on PET.

9. Structured report example

10. Take-home points

1. Justify every scan and dose by weight: 2.96–5.2 MBq/kg FDG (North America 2024) or the EANM card; tailor the CT to the question.
2. In paediatric HL, the ERA PET decides radiotherapy; report the Deauville score, qPET and the protocol threshold.
3. Isolated smooth thymic regrowth after therapy is almost always rebound; relapse brings other growing masses.
4. Use ¹²³I-MIBG with SIOPEN or Curie scoring for neuroblastoma; switch to FDG for the roughly 10% of tumours that are MIBG-non-avid.
5. Post-induction SIOPEN > 3 or Curie > 2 predicts poor outcome.
6. FDG PET/CT stages rhabdomyosarcoma and Ewing sarcoma; lung nodules belong to CT.
7. In LCH, FDG is the most sensitive functional test, but keep the same bone method throughout follow-up.

Test yourself

5 quick questions. Pick an answer to see the explanation.

References

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