About Dr. Zhu Chao
Dr. Zhu Chao is Chief of Nuclear Medicine at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — one of China's foremost nuclear medicine departments and a national reference centre for molecular imaging, PET-CT diagnostics, and theranostic oncology. He is a nationally recognised leader in oncological PET-CT imaging, thyroid cancer management, and the clinical application of novel molecular probes including fibroblast activation protein inhibitor (FAPI) tracers, PSMA-targeted imaging, and peptide receptor radionuclide therapy. Dr. Zhu's practice is defined by the philosophy that nuclear medicine is no longer a supporting discipline in oncology — it is a central decision-making tool that determines treatment strategy, monitors therapeutic response, and enables theranostic approaches that combine diagnosis and targeted radionuclide therapy in a single molecular framework. His department at Ruijin Hospital operates in full compliance with European Association of Nuclear Medicine (EANM) standards, ensuring image quality, quantitative reproducibility, and diagnostic consistency that meets international benchmarks for patients from any country.
Case Overview
Ms. Catherine Moreau, a 54-year-old French architect based in Shanghai, presented two years after total thyroidectomy and central neck dissection for papillary thyroid carcinoma with a progressive rise in serum thyroglobulin (Tg 15.8 ng/mL under TSH suppression) — the biochemical signature of recurrent or metastatic thyroid cancer — in the complete absence of any abnormality on neck ultrasound, chest CT, or conventional radioiodine whole-body scan. This combination — rising Tg with negative conventional imaging and negative radioiodine scan — is one of the most diagnostically challenging scenarios in thyroid oncology, indicating probable tumour dedifferentiation with loss of iodine-concentrating ability.
Dr. Zhu Chao recommended dual-tracer molecular imaging: FDG PET-CT to detect metabolically active disease, and 68Ga-FAPI-04 PET-CT — a novel probe targeting fibroblast activation protein (FAP) overexpressed in the tumour microenvironment — to characterise the tumour biology and detect lesions invisible to FDG. FDG PET-CT identified multiple pulmonary nodules and a right seventh rib lesion with moderate metabolic activity. FAPI PET-CT revealed the same lesions with dramatically higher tracer uptake (SUVmax 12.8–18.5 versus 4.5–6.2 on FDG) and — critically — identified a 5 mm lymph node near the hepatic round ligament that was FDG-negative and invisible on all prior imaging. The dual-tracer findings established the diagnosis of radioiodine-refractory recurrent papillary thyroid carcinoma with pulmonary, osseous, and occult nodal metastases, and guided a theranostic treatment strategy: high-dose radioiodine re-differentiation attempt followed by lenvatinib plus PD-1 immunotherapy. At three months, FAPI PET-CT demonstrated a 60% reduction in pulmonary lesion SUVmax and Tg had fallen from 15.8 to 2.1 ng/mL — partial remission confirmed.
Patient Background
- Name / Nationality: Ms. Catherine Moreau (pseudonym) — French; architect based in Shanghai; two years post total thyroidectomy for papillary thyroid carcinoma
- Age / Sex: 54-year-old female
- Chief Complaint: Progressive rise in serum thyroglobulin (Tg) over six months under TSH suppression therapy; no localising symptoms; conventional imaging negative
- Surgical history: Total thyroidectomy plus central compartment lymph node dissection two years prior; post-operative radioiodine ablation completed; on levothyroxine suppression therapy since surgery
- Current medications: Levothyroxine — dose titrated to maintain TSH below 0.1 mIU/L
- Past medical history: No other significant medical history; no drug allergies
Laboratory and Conventional Imaging Assessment
Laboratory Results
- Serum thyroglobulin (Tg): 15.8 ng/mL under TSH suppression (TSH 0.05 mIU/L) — significantly elevated; any detectable Tg after total thyroidectomy indicates residual or recurrent thyroid tissue or tumour
- Anti-thyroglobulin antibody (TgAb): Negative — confirms that the Tg measurement is not falsely elevated by antibody interference; the Tg value is reliable
- TSH: 0.05 mIU/L — adequately suppressed
- Trend: Progressive rise over six months — doubling time consistent with active tumour growth rather than stable remnant tissue
Conventional Imaging — All Negative
- Neck ultrasound: Post-surgical anatomical distortion; no definite lymph node with malignant morphological features identified
- Enhanced chest CT: Multiple bilateral pulmonary micronodules less than 3 mm in diameter — below the size threshold for confident characterisation as metastatic; indeterminate
- Conventional 131I whole-body scan (WBS): Negative — no abnormal radioiodine uptake identified anywhere in the body; defines radioiodine-refractory disease
- Clinical interpretation: Rising Tg with negative WBS is the hallmark of radioiodine-refractory thyroid cancer — affecting approximately 5–15% of patients with differentiated thyroid carcinoma. Standard radioiodine therapy is ineffective; alternative staging and treatment strategies are required.
Dr. Zhu's diagnostic assessment: The combination of rising Tg and negative WBS tells us two things with certainty. First, there is active thyroid cancer somewhere in this patient's body. Second, the cancer has lost its ability to concentrate iodine — which means our standard treatment tool is no longer available. FDG targets glucose metabolism — upregulated in dedifferentiated thyroid cancer. FAPI targets the tumour microenvironment — present in virtually all solid tumours regardless of differentiation status. Together, they give us a complete biological portrait of the disease.
Advanced Molecular Imaging — Dual-Tracer PET-CT
18F-FDG PET-CT
FDG (fluorodeoxyglucose) accumulates in cells with high glycolytic activity — a metabolic hallmark of malignant cells. In differentiated thyroid cancer, FDG uptake is inversely correlated with iodine avidity: tumours that have lost iodine-concentrating ability typically show increased FDG uptake — the so-called flip-flop phenomenon. This makes FDG PET-CT the first-line functional imaging tool for radioiodine-refractory thyroid cancer.
- Pulmonary findings: Multiple nodular foci of increased FDG uptake in both lungs; SUVmax range 4.5–6.2; consistent with haematogenous pulmonary metastases
- Osseous findings: Focal FDG uptake in the right seventh rib; SUVmax 5.1; consistent with osteolytic bone metastasis
- Nodal findings: No FDG-avid lymph nodes identified — the 5 mm hepatic round ligament node was below the FDG detection threshold
- Interpretation: Pulmonary and osseous metastases confirmed; nodal disease not detected by FDG
68Ga-FAPI-04 PET-CT — Ruijin Hospital Signature Capability
FAPI tracers target fibroblast activation protein (FAP) — a serine protease selectively overexpressed on cancer-associated fibroblasts (CAFs) within the tumour stroma. CAFs are a major component of the tumour microenvironment in most solid tumours, and their FAP expression is largely independent of tumour differentiation status. This means FAPI tracers can detect tumours that have lost the biological markers targeted by conventional tracers.
- Pulmonary findings: All pulmonary nodules demonstrated markedly higher FAPI uptake; SUVmax range 12.8–18.5 — two to three times higher than FDG; tumour-to-background ratio excellent
- Osseous findings: Right seventh rib lesion; SUVmax 14.2; significantly higher than FDG uptake
- Critical occult finding — hepatic round ligament lymph node: A 5 mm lymph node adjacent to the hepatic round ligament — invisible on neck ultrasound, chest CT, and FDG PET-CT — demonstrated intense focal FAPI uptake (SUVmax 11.6); this micrometastatic nodal deposit would have been entirely missed by all conventional and FDG-based imaging, and its detection fundamentally altered the staging and treatment planning
- Interpretation: FAPI PET-CT upstaged the disease by identifying occult nodal metastasis not detected by any other modality; confirmed high tumour stroma burden consistent with aggressive biological behaviour
Dr. Zhu's imaging interpretation: The FAPI result is striking in two ways. First, the absolute SUVmax values — up to 18.5 — are among the highest we see in thyroid cancer. This tells us the tumour microenvironment is extremely active. Second, the 5 mm node near the hepatic round ligament. On FDG, it is invisible. On FAPI, it lights up like a beacon. That node changes the staging from M1 pulmonary and osseous to M1 pulmonary, osseous, and nodal — and it changes the treatment plan, because a node in that location must be managed systemically. Without FAPI, we would have planned treatment for two sites and missed a third.
Multidisciplinary Team Discussion and Treatment Strategy
The MDT convened by Dr. Zhu Chao included nuclear medicine, endocrinology, oncology, and radiation oncology. The dual-tracer PET-CT findings established the revised diagnosis: radioiodine-refractory recurrent papillary thyroid carcinoma with pulmonary, osseous, and occult nodal metastases — a systemic disease requiring systemic treatment. The treatment strategy was designed around the theranostic principle: use the molecular imaging findings not only to stage the disease but to select the treatment modality most likely to be effective based on the biological characteristics of each lesion.
Step 1 — Radioiodine Re-differentiation Attempt
Despite the negative WBS, the moderate FDG uptake in the pulmonary lesions suggested residual differentiation capacity might be present. A high-dose radioiodine challenge under maximal TSH stimulation was attempted.
TSH stimulation protocol: Levothyroxine discontinued for four weeks; recombinant human TSH (rhTSH, Thyrogen) injected on days 1 and 2 to achieve TSH above 30 mIU/L. rhTSH stimulation avoids the hypothyroid symptoms associated with levothyroxine withdrawal.
High-dose radioiodine therapy: 131I 200 mCi administered orally under radiation safety isolation.
Post-therapy SPECT/CT (one week): Low-level iodine uptake demonstrated in two of the pulmonary nodules — confirming partial re-differentiation. The right seventh rib lesion showed no iodine uptake — confirming complete radioiodine resistance at this site.
Dr. Zhu's assessment: The post-therapy scan gives us the answer we needed. Some of the lung lesions can still take up iodine — a little, but enough to confirm partial re-differentiation. The rib lesion takes up nothing. This is the heterogeneity that makes radioiodine-refractory thyroid cancer so difficult: different lesions in the same patient have different biological behaviours. We need a systemic agent that works regardless of iodine avidity.
Step 2 — Systemic Targeted Therapy: Lenvatinib Plus PD-1 Immunotherapy
Given the partial radioiodine response in pulmonary lesions and complete radioiodine resistance in the osseous lesion, the MDT recommended systemic targeted therapy. Lenvatinib — a multi-kinase inhibitor targeting VEGFR1-3, FGFR1-4, PDGFRalpha, RET, and KIT — is the first-line systemic agent for radioiodine-refractory differentiated thyroid cancer per NCCN and ESMO guidelines, with progression-free survival benefit demonstrated in the SELECT trial. PD-1 checkpoint inhibitor immunotherapy was added based on the high FAPI uptake indicating an active tumour microenvironment and emerging evidence for synergy between anti-angiogenic TKIs and PD-1 blockade.
Three-Month Response Assessment
68Ga-FAPI PET-CT Restaging
- Pulmonary lesions: SUVmax reduced from 12.8–18.5 to approximately 6.0 — approximately 60% reduction; lesion volumes reduced on CT component
- Osseous lesion (right seventh rib): Marked reduction in FAPI uptake; CT showing sclerotic change consistent with treatment response
- Hepatic round ligament node: FAPI uptake reduced to near-background levels — near-complete metabolic response in the previously occult micrometastatic node
- Overall response: Partial remission (PR) per PERCIST criteria
Biochemical Response
- Serum Tg: Reduced from 15.8 to 2.1 ng/mL — 87% reduction; biochemical partial response confirmed
- TSH: Maintained below 0.1 mIU/L on resumed levothyroxine suppression
Dr. Zhu noted that the FAPI PET-CT metabolic response was detectable at three months, approximately four to six weeks before the anatomical CT demonstrated measurable size reduction in the pulmonary nodules — demonstrating the early response detection advantage of functional PET imaging over anatomy-based CT.
Expert Commentary — Dr. Zhu Chao
1. The Rising Tg, Negative Imaging Dilemma: Molecular Imaging as the Solution
Rising thyroglobulin with negative conventional imaging is not a diagnostic failure — it is a diagnostic indication. It tells us that the disease is present but below the detection threshold of anatomy-based imaging, and that we need to switch to biology-based imaging to find it. The flip-flop phenomenon in thyroid cancer — where loss of iodine avidity is accompanied by gain of FDG avidity — means that FDG PET-CT is the correct next step when WBS is negative and Tg is rising. But FDG has its own limitations: it requires a minimum lesion size and metabolic rate to generate a detectable signal. FAPI addresses these limitations by targeting the tumour microenvironment rather than the tumour cells themselves. The CAFs that express FAP are present in virtually all solid tumours, are metabolically active regardless of tumour differentiation status, and generate a high-contrast signal even in small lesions. The 5 mm node in this case — invisible to FDG, visible to FAPI — is the clearest possible demonstration of why dual-tracer imaging is superior to single-tracer imaging in radioiodine-refractory thyroid cancer.
2. Theranostics: Diagnosis and Treatment from the Same Molecular Target
The theranostic principle — using the same molecular target for both imaging and therapy — is the most important conceptual advance in nuclear medicine in the past two decades. The PSMA theranostic pair (68Ga-PSMA for imaging, 177Lu-PSMA-617 for therapy) has transformed the management of metastatic prostate cancer. The DOTATATE theranostic pair has done the same for neuroendocrine tumours. FAPI is the next frontier: 68Ga-FAPI-04 for imaging, 177Lu-FAPI for therapy — targeting the tumour microenvironment rather than the tumour cells, applicable across a much broader range of tumour types. In this case, the high FAPI uptake (SUVmax up to 18.5) identifies this patient as a potential candidate for FAPI-targeted radionuclide therapy if the lenvatinib-based regimen eventually fails. The imaging result is not just a staging tool — it is a treatment eligibility assessment for a future therapeutic option. That is theranostics: every imaging study is simultaneously a potential treatment selection study.
3. Quantitative PET: SUVmax as a Biomarker, Not Just a Number
The shift from qualitative PET interpretation to quantitative PET analysis (SUVmax, SUVmean, metabolic tumour volume, total lesion glycolysis) represents a fundamental maturation of nuclear medicine as a clinical discipline. SUVmax is not just a measure of tracer uptake — it is a surrogate biomarker for tumour biological activity. A high baseline SUVmax predicts aggressive behaviour, rapid progression, and poor prognosis. A large percentage reduction in SUVmax after treatment predicts durable response and improved survival. In this case, the baseline FAPI SUVmax of 12.8–18.5 predicted the aggressive behaviour that conventional imaging had failed to reveal. The three-month reduction to approximately 6.0 — a 60% decline — is a strong predictor of continued response. At Ruijin Hospital, we report SUVmax, SUVmean, metabolic tumour volume, and total lesion activity for every oncological PET study — because the number matters as much as the image, and the change in the number over time matters more than either.
4. EANM Standards and International Reproducibility
For international patients who will have PET-CT imaging in Shanghai and follow-up imaging in their home country, the reproducibility of quantitative PET measurements across institutions is not a technical detail — it is a clinical necessity. EANM standardisation — covering patient preparation (fasting duration, blood glucose control, quiet rest period, hydration), scanner calibration, image reconstruction parameters, and reporting conventions — ensures that a SUVmax measured at Ruijin Hospital means the same thing as a SUVmax measured at any EANM-compliant centre in Europe or North America. International patients deserve imaging results that their physicians anywhere in the world can interpret, compare, and act upon with confidence.
How CMCS Shanghai Coordinated This Case
CMCS Shanghai supported Ms. Moreau from initial Tg alert through three-month response assessment, including: urgent coordination of comprehensive thyroid function panel, TgAb, and Tg quantification with bilingual results interpretation; specialist referral to Dr. Zhu Chao at Ruijin Hospital's Department of Nuclear Medicine with priority consultation scheduling; coordination of FDG PET-CT and 68Ga-FAPI-04 PET-CT dual-tracer imaging with patient preparation instructions in English and French (fasting protocol, glucose monitoring, levothyroxine timing); bilingual interpretation of all PET-CT reports including SUVmax values, lesion characterisation, and staging implications; real-time communication of the occult hepatic round ligament node finding to the patient and her endocrinologist in France; MDT discussion coordination involving nuclear medicine, endocrinology, oncology, and radiation oncology with bilingual summary for the patient; rhTSH stimulation protocol coordination including levothyroxine withdrawal scheduling, rhTSH injection appointments, and radiation safety isolation arrangements for the 200 mCi radioiodine treatment; post-therapy SPECT/CT coordination one week after radioiodine administration with results communicated to the patient's thyroid oncologist in Paris; lenvatinib access coordination including drug procurement, dose initiation, and tolerability monitoring protocol; PD-1 immunotherapy infusion scheduling and immune-related adverse event monitoring; three-month FAPI PET-CT restaging coordination with quantitative SUVmax comparison report and Tg trend analysis communicated to the patient and her overseas physicians; and establishment of a long-term surveillance protocol with six-monthly FAPI PET-CT and Tg monitoring, with direct liaison between Dr. Zhu's team and the patient's endocrinologist and oncologist in France.
For international patients with thyroid cancer, neuroendocrine tumours, or any malignancy requiring advanced molecular imaging, PET-CT staging, or theranostic evaluation in Shanghai, Dr. Zhu Chao's team at Ruijin Hospital represents nuclear medicine expertise at the international frontier — combining dual-tracer PET-CT with novel FAPI probes, quantitative SUV analysis to EANM standards, and theranostic treatment planning to find what conventional imaging misses and guide treatment decisions that conventional oncology cannot make alone. CMCS ensures that expertise is accessible: in the patient's language, with overseas physicians receiving quantitative imaging reports they can directly compare with follow-up studies anywhere in the world.
This case report is de-identified and published for educational purposes. All clinical details have been anonymized in accordance with patient privacy standards. CMCS Shanghai is a medical concierge service and does not provide direct medical care.
0 comments