# FCH PET/CT Imaging for Parathyroid Gland Detection: A Patient's Guide to Modern Pre-Surgical Scanning

Researchers reviewed over a decade of evidence on a modern imaging technique called FCH PET/CT, which uses a radioactive tracer to pinpoint overactive parathyroid glands before surgery. The procedure detects abnormal parathyroid glands with about 97% sensitivity overall, outperforming both ultrasound (47% positivity) and traditional MIBI scintigraphy (37% positivity) in real-world settings. For patients with primary hyperparathyroidism, this imaging method enables minimally invasive surgery, reduces the risk of failed operations, and has proven cost-effective in both the United States and Europe. The authors recommend FCH PET/CT as the first-line radionuclide imaging technique for all patients with hyperparathyroidism who are candidates for surgery.

# FCH PET/CT Imaging for Parathyroid Gland Detection: A Patient's Guide to Modern Pre-Surgical Scanning

## Table of Contents

- Key Points
- Understanding Hyperparathyroidism and the Parathyroid Glands
- The Evolution of Parathyroid Imaging
- How FCH PET/CT Works: The Science Explained
- How This Research Was Conducted
- Key Findings: How Well Does FCH PET/CT Perform?
- Detecting Multiple Gland Disease
- Imaging After Failed or Previous Surgery
- Rare Cases: Parathyroid Carcinoma
- Cost-Effectiveness: Is It Worth It?
- What This Means for Patients
- Study Limitations
- Recommendations for Patients
- Frequently Asked Questions
- Source Information

## Key Points

- FCH PET/CT detects abnormal parathyroid glands with about 97% sensitivity, outperforming ultrasound (47%) and MIBI (37%) in real-world settings.
- In a randomized trial, FCH-guided surgery achieved normal calcium at one month in 85% of patients versus 56% with MIBI guidance.
- FCH PET/CT detects multiple gland disease better than MIBI, reducing the risk of a missed gland and repeat surgery.
- For recurrent or persistent hyperparathyroidism after surgery, FCH PET/CT had 78% positivity, similar to first-time surgery, and outperformed 4D-CT.
- Cost-effectiveness models in the US and Netherlands found FCH PET/CT worthwhile despite higher imaging costs, because it prevents failed operations.

## Understanding Hyperparathyroidism and the Parathyroid Glands

Hyperparathyroidism (HPT) is a condition in which one or more of the parathyroid glands produce too much parathyroid hormone (PTH). These four small glands — two superior and two inferior — are normally located behind the thyroid gland in the neck. They regulate calcium levels in your blood. When they become overactive (hyperfunctioning), calcium levels rise, which can lead to kidney stones, bone thinning, fatigue, and other health problems.

Anatomical studies show that **81.4% of people have exactly four parathyroid glands** (two superior and two inferior). Interestingly, five or more glands are found in **4.9% of healthy individuals and 6.3% of patients with HPT**.

The location of these glands matters greatly for surgery. The superior glands, which develop from the 4th pharyngeal pouch, usually stay close to the upper pole of the thyroid. In less than 1% of cases, they migrate above the upper thyroid pole. The inferior glands, which develop from the 3rd pharyngeal pouch, travel much farther during embryonic development — potentially from the angle of the jaw all the way down to the heart sac (pericardium). In approximately 2% of cases, these inferior glands end up above the upper thyroid pole.

Because of this wide range of travel, parathyroid glands can end up in unexpected places called "ectopic" locations. According to a recent meta-analysis cited in this article:

-
**15.9%** of parathyroid glands are in ectopic locations
-
**11.6%** are ectopic but still in the neck, including:

- 3.6% in the retroesophageal/paraesophageal space (behind the esophagus)
- 2.4% inside the thyroid gland itself
- 2.1% in the carotid sheath (around the major neck artery)
- 2.0% in the thyrothymic ligament
- 0.6% in the tracheoesophageal groove (between windpipe and esophagus)
- 1.0% in other neck locations

-
**4.3%** are in the mediastinum (the area between the lungs), most commonly within the thymus gland

This is why accurate preoperative imaging is essential — it helps surgeons know exactly where to look. With modern preoperative localization studies, the rate of failed parathyroidectomy (PTX) surgery, particularly due to unsuspected multiple-gland disease or ectopic glands, has dropped dramatically.

## The Evolution of Parathyroid Imaging

Doctors have long known that combining an anatomical imaging method with a functional one gives the best results for parathyroid surgery planning. The history of parathyroid imaging shows steady progress over four decades:

**The 1980s:** Thallium-201 (201Tl) scanning was used, combined with technetium-99m-pertechnetate to subtract thyroid activity. In one operated series, the success rate reached 92% among 24 patients, but two of four sub-centimeter abnormal glands were missed. Thallium had poor imaging characteristics, including suboptimal photon energy (69-81 keV) and a long physical half-life of 73 hours, exposing patients to unacceptably high whole-body radiation. **201Tl is no longer recommended for parathyroid imaging.**

**Late 1980s onward:** Technetium-99m-sestaMIBI (MIBI) scintigraphy became the standard functional imaging method. Over the years, it was refined with dual-phase studies, thyroid uptake subtraction with 99mTc-pertechnetate or preferably 123I, and eventually SPECT/CT (single photon emission computed tomography combined with X-ray CT).

**The PET era:** Positron emission tomography (PET) offers better image resolution than SPECT. In 1964, methionine labeled with 75Se was tried, then abandoned. Thirty years later, 11C-methionine was proposed for PET imaging of parathyroid glands. However, evidence showed it was less effective than a fluorinated choline analog called **18F-fluorocholine (FCH)**, introduced for this purpose in 2014. In the same year, 11C-choline was also reported as a PET tracer for parathyroid adenoma localization in 40 patients. A comparative study of 32 patients with negative first-line imaging found 11C-choline PET/CT superior to 11C-methionine. In 12 of 14 patients where FCH PET/CT had been negative or inconclusive, 11C-choline identified a suspicious lesion.

However, 11C-labeled tracers have a very short half-life of just 20 minutes. This means lower radiation exposure for patients — but it requires an on-site cyclotron and a GMP radiopharmacy facility, which is logistically difficult and available in very few PET centers. **FCH, by contrast, is widely available** with no such infrastructure requirements.

## How FCH PET/CT Works: The Science Explained

Choline is a natural compound that all cells need to build phospholipids — the essential building blocks of cell membranes. When choline enters a cell, the enzyme choline kinase converts it to phosphorylcholine, which eventually becomes phosphatidylcholine (lecithin), a key membrane component.

FCH is a fluorinated version of choline that closely follows the same metabolic pathway. Cancer cells and overactive parathyroid cells have increased choline kinase activity, which is why they take up FCH more avidly than normal tissues. This "hot spot" of radioactivity can then be seen on the PET scan.

FCH has been used in Europe for more than 20 years, primarily for detecting prostate and hepatocellular carcinoma. In 2010, it received marketing authorization in France for oncologic imaging. It was initially approved for parathyroid imaging in France in January 2024. Interestingly, over a decade ago, several European teams noticed incidental "hot spots" on FCH PET/CT scans performed for prostate cancer — these turned out to be overactive parathyroid glands. Some of those patients had undiagnosed HPT, which was then confirmed, and surgery confirmed that the FCH focus matched an abnormal parathyroid gland.

The European Association of Nuclear Medicine (EANM) now explicitly recommends FCH PET/CT for detecting abnormal parathyroid glands in its 2021 guideline on parathyroid imaging.

## How This Research Was Conducted

This article is a comprehensive review that combines published evidence with the authors' real-world experience. The team analyzed data from their own institutions — Hôpital Tenon in Paris, France, where they have used FCH PET/CT for parathyroid imaging for **12 years**, and Bratislava, Slovakia, where they have used it for **11 years**.

The review covers multiple study types, including randomized controlled trials, retrospective analyses, and prospective cohort studies. Key studies analyzed include:

- The APACH2 randomized trial comparing FCH PET/CT head-to-head with MIBI SPECT/CT
- A partial retrospective analysis of 323 FCH PET/CT scans for primary HPT (pHPT) and 78 for renal HPT (rHPT) from Hôpital Tenon
- A retrospective study by Broos et al. of 271 patients undergoing first-line FCH PET/CT
- A prospective study by Cuderman et al. of 103 patients who underwent both FCH PET/CT and MIBI scintigraphy
- Cost-effectiveness modeling studies from both US and Dutch healthcare systems

## Key Findings: How Well Does FCH PET/CT Perform?

The headline finding is striking: FCH PET/CT has a **sensitivity of 97% (range 96%-98%)** for detecting abnormal parathyroid glands in primary HPT. This consistently outperforms other radiopharmaceuticals, ultrasound, and 4D-CT.

**Positivity rates in the Hôpital Tenon series:**

- FCH PET/CT as first-line imaging: **67% positivity** (CI: 56-76) in 96 examinations
- FCH PET/CT performed later in the work-up: **75% positivity** (CI: 70-80) in 305 examinations
- MIBI scintigraphy: **37% positivity** (CI: 30-44)
- Ultrasound: **47% positivity** (CI: 42-52)

The lower rates for MIBI and ultrasound were influenced by selection bias — patients were typically referred for FCH PET/CT specifically because MIBI and ultrasound had been inconclusive or discordant. Even so, FCH performed better.

**Broos et al. — first-line FCH PET/CT in 271 patients with pHPT:**

- Positivity rate: **75%**

- Correct detection rate: **96% patient-based** and **90% lesion-based**

**Another recent study of 271 patients with overt pHPT reported:**

- Sensitivity: **99%**

- Specificity: **91%**

- Positive predictive value (PPV): **100%**

- Negative predictive value (NPV): **80%**

- Accuracy: **99%**

**The APACH2 randomized trial:** In this trial, 57 patients with pHPT who needed functional imaging before their first parathyroidectomy were randomized: 29 to FCH PET/CT and 28 to MIBI SPECT/CT.

- Positivity rate: **83% (24/29) for FCH** vs **64% (18/28) for MIBI**

- Sensitivity: **82% (CI: 62-93) for FCH** vs **63% (CI: 42-80) for MIBI**

- Normal calcium levels one month after imaging-guided minimally invasive surgery: **85% (23/27) in the FCH group** vs **56% (14/25) in the MIBI group**

This last point is critically important for patients — it means that when FCH PET/CT guided the surgery, the operation was more likely to successfully cure the disease, with normal calcium levels achieved in a substantially higher proportion of patients one month after surgery.

## Detecting Multiple Gland Disease (MGD)

Multiple gland disease (MGD) — the presence of more than one overactive parathyroid gland — occurs in **15% to 20% of primary HPT patients**. This is a high-risk situation because if surgery removes only the one visible abnormal gland (minimally invasive parathyroidectomy), the remaining abnormal glands can cause disease recurrence.

In the Hôpital Tenon analysis, **29 of 167 pHPT patients (17%) had histologically proven MGD**. Of these 29 patients, 21 (72%) underwent FCH PET/CT because MIBI and ultrasound had been inconclusive or discordant. Given this strong selection bias, the patient-based sensitivity for MGD was **38% for FCH vs 0% for MIBI** — MIBI failed to detect any case of MGD in this group. In fact, 38% of MGD cases appeared as a single abnormal focus on MIBI SPECT, with discordant ultrasound results. In those patients, a MIBI-based strategy would not have prompted FCH PET/CT to detect the additional abnormal glands.

Other studies confirm FCH's superiority in MGD:

- One short series found that four MGDs among 17 pHPT patients appeared as a single focus on scintigraphy in three cases, whereas FCH correctly localized six abnormal glands in three patients, leading to successful surgery.
- Another study reported that **9 of 15 MGDs were recognized on FCH PET/CT vs only 4 on MIBI scintigraphy**.
- The prospective study by Cuderman et al. included 103 patients with pHPT who underwent both FCH PET/CT and MIBI scintigraphy with a comprehensive protocol. Histology revealed **14 patients (14%) with MGD**, consisting of 4 dual adenomas and 31 hyperplastic glands. In this subgroup, FCH PET/CT had a sensitivity of **88% and specificity of 100%**, whereas MIBI scintigraphy had a sensitivity of only **44%**. FCH PET/CT revealed MGD in **6 of 14 patients (43%)** who had been falsely classified as having a single abnormal gland on MIBI.

FCH is also particularly good at detecting hyperplastic parathyroid glands (enlarged but not adenomatous glands), which are notoriously difficult to find with MIBI and ultrasound. In a series localizing **155 hyperplastic parathyroid glands**, the sensitivity of FCH PET/CT was **72%, versus 39% for ultrasound and 25% for MIBI**.

For patients with renal (secondary) HPT, FCH is even more valuable. In the Hôpital Tenon series, MGD was expected and detected by FCH PET/CT in **88% of patients with renal HPT**. This matters because renal HPT patients almost always have multiple overactive glands.

Another study of 64 patients with positive MIBI scans found that subsequent FCH PET/CT identified **nine additional abnormal glands not detected by MIBI in eight patients (12.5%)**, including 4 patients with MGD. Additionally, a negative FCH PET/CT allowed reassessment of **eight false-positive MIBI results in seven patients (11%)**. Only one abnormal gland was missed by FCH and correctly identified by MIBI.

Given these findings, the authors state that first-line FCH PET/CT is especially indicated when there is a high likelihood of hyperplastic glands, including persistent or recurrent primary HPT related to MGD, renal HPT, and hereditary HPT, particularly multiple endocrine neoplasia type 1 (MEN1).

## Imaging After Failed or Previous Surgery

When HPT persists or recurs after parathyroidectomy, finding the remaining abnormal gland(s) is crucial before recommending reoperation, because repeat surgery carries a high risk of complications. The Hôpital Tenon data showed that FCH PET/CT performed nearly identically in this challenging setting:

- Patient-based positivity: **78% (42/54)** in patients with suspected persistence/recurrence vs **84% (291/347)** in patients without prior surgery — not a statistically significant difference
- Gland-based sensitivity: **89% (24/27)** vs **91% (169/186)** — again, no significant difference

FCH PET/CT also outperformed 4D-CT in this setting. In a study by Latgé et al., **37 patients with persistent or recurrent pHPT** underwent both FCH PET/CT and 4D-contrast-enhanced CT (4D-CeCT):

- FCH PET/CT: **88% positivity rate and 95% sensitivity**

- 4D-CeCT: **63% positivity rate and 70% sensitivity**

- Dynamic 4D-CeCT identified no additional glands missed by PET/CT
- Combining the two techniques did not improve detection or sensitivity

The authors therefore conclude that **recurrent or persistent HPT after parathyroidectomy is a clear indication for FCH PET/CT**.

## Rare Cases: Parathyroid Carcinoma

In rare cases, persistent pHPT after surgery is caused by parathyroid carcinoma — a rare malignant endocrine tumor. According to the "3+3 rule" and a recent review, malignant pHPT should be suspected when:

- Serum PTH levels are **3 to 10 times above the upper limit of normal**

- Calcium levels are markedly elevated (**greater than 3 mmol/L**)
- Lesion size is **greater than 3 cm**, possibly palpable in the neck
- Ultrasound shows inhomogeneous, hypoechoic, and lobulated masses
- Severe bone disease (osteitis fibrosa cystica) or kidney disease (renal stones and nephrocalcinosis) is present

Parathyroid carcinoma tends to recur and metastasize, so routine postoperative follow-up is essential. FCH PET/CT was first reported in 2015 in a patient with recurrent parathyroid carcinoma, where it detected disease better than FDG PET/CT and various scintigraphic methods. Subsequent case reports confirmed that both FCH and FDG PET/CT can detect recurrent parathyroid carcinoma lesions, as well as synchronous recurrence of another malignancy. The authors note that FCH PET/CT guides surgeons to perform selective metastasectomy in these cases.

## Cost-Effectiveness: Is FCH PET/CT Worth It?

Although FCH is more expensive per dose than MIBI, recent studies show the procedure is still cost-effective because of its superior diagnostic performance.

**Yap et al. — US healthcare system model:** This decision-tree analysis modeled patients undergoing parathyroidectomy for pHPT using one of four preoperative localization approaches: FCH PET/CT, 4D-CT, ultrasound, or MIBI SPECT.

- FCH PET/CT gained the most quality-adjusted life-years (QALYs): **23.9**

- It was also the costliest imaging procedure at **$2,096**

- However, the total treatment cost was **$11,245, or $470 per quality-adjusted life-year gained**

- MIBI SPECT and ultrasound were "dominated strategies" — meaning they were both less effective and more costly overall

**Van Mossel et al. — Dutch healthcare system:** This study compared two strategies: a "one-stop shop" approach with FCH PET/CT for all patients vs using FCH PET/CT only after negative or inconclusive MIBI SPECT/CT. Simulated long-term health effects and costs were **similar for both strategies**.

The authors also note that the argument about limited PET scanner availability is becoming less valid with the rapid global expansion of PET technology.

## What This Means for Patients

For patients with confirmed hyperparathyroidism who are scheduled for surgery, this research has several meaningful implications.

**Better surgical outcomes:** The APACH2 trial's finding — 85% of FCH-guided patients achieved normal calcium at one month vs 56% of MIBI-guided patients — translates directly into fewer failed operations and fewer repeat surgeries.

**More minimally invasive surgery:** Accurate localization allows more patients to undergo minimally invasive parathyroidectomy (MIPTX), which shortens operative time, reduces incision length, and lowers surgical risks compared with traditional bilateral neck exploration.

**Fewer missed glands:** FCH PET/CT detects multiple gland disease far better than MIBI. This reduces the chance that a patient will need a second operation for an abnormal gland that was missed the first time.

**Lower cumulative radiation:** Compared with undergoing both MIBI SPECT/CT and then FCH PET/CT sequentially, a single FCH PET/CT means shorter patient mobilization and lower overall radiation exposure.

**Caution on blood test levels:** The article notes that while higher serum PTH levels tend to produce clearer FCH PET results, researchers could not determine reliable cutoff values for PTH or calcium that would predict a positive or negative FCH scan. Interestingly, in 2011 studies, **5.5-7% of pHPT patients undergoing surgery had normal basal PTH levels**. For patients with suggestive symptoms but normal PTH and calcium, a calcium load test can help confirm the diagnosis, and FCH PET/CT remains a useful tool in this "mild" HPT setting.

## What This Study Couldn't Prove

As with any review, there are limitations to acknowledge.

Much of the evidence comes from retrospective, real-world series with inherent selection bias — patients were often referred for FCH PET/CT precisely because MIBI and ultrasound had failed. This bias likely understates FCH's true performance relative to older methods in unselected patients.

The evidence for FCH PET/CT in **renal HPT** is based on fewer series than for primary HPT, so the strength of the recommendation is somewhat lower in that setting.

The authors could not identify clinical or biochemical parameters (like specific PTH or calcium cutoff values) that would reliably predict who benefits most from FCH PET/CT.

Finally, while the review draws on over a decade of real-world experience, most comparative data against MIBI come from a single randomized controlled trial (APACH2) with a relatively small sample size of 57 patients.

## Recommendations for Patients

Based on this comprehensive review, here is the practical guidance that emerges:

1.
**If you have biochemically confirmed HPT and surgery is planned, ask your care team about FCH PET/CT as a first-line imaging option** — not just as a backup when ultrasound or MIBI fails. The evidence supports first-line use in all types of HPT, including primary, renal, persistent, and recurrent disease.
1.
**If you have had a previous failed parathyroidectomy**, FCH PET/CT is particularly valuable for locating the remaining abnormal gland(s) before reoperation, given the high complication risk of repeat surgery.
1.
**If you have renal (secondary) HPT or a hereditary condition like MEN1**, FCH PET/CT is strongly recommended because of its superior ability to detect multiple hyperplastic glands, which are common in these conditions.
1.
**If you were told your MIBI scan was negative or inconclusive**, this does not mean imaging cannot help you. FCH PET/CT successfully localizes abnormal glands in many patients with negative MIBI results.
1.
**Discuss the "one-stop shop" approach with your surgeon** — going straight to FCH PET/CT may avoid multiple rounds of imaging and reduce total radiation exposure, with similar or better cost-effectiveness compared with sequential imaging strategies.
1.
**If parathyroid carcinoma is suspected** (based on very high PTH, calcium >3 mmol/L, or a neck mass larger than 3 cm), FCH PET/CT can help guide surgical planning and detect recurrent or metastatic disease.

Every patient's situation is unique, and imaging decisions should always be made together with your endocrinologist and surgeon. But the evidence in this review strongly supports the growing role of FCH PET/CT as the first-line nuclear medicine imaging technique for all types of hyperparathyroidism when surgery is being considered.

## Frequently Asked Questions

### What is FCH PET/CT and how does it work?

FCH PET/CT is a modern imaging scan that uses a radioactive form of choline to locate overactive parathyroid glands before surgery. Overactive parathyroid cells take up this tracer more avidly than normal tissue, creating a 'hot spot' that appears on the scan. This helps surgeons know exactly where to look, improving surgical planning.

### How accurate is FCH PET/CT compared with ultrasound or MIBI scans?

FCH PET/CT detects abnormal parathyroid glands with about 97% sensitivity overall. In real-world data, ultrasound was positive in 47% of cases and MIBI scintigraphy in 37%. FCH PET/CT consistently outperformed these older methods, meaning it is more likely to find the problem gland before surgery.

### Will FCH PET/CT reduce my chance of needing a second surgery?

Yes. In a randomized trial, 85% of patients whose surgery was guided by FCH PET/CT had normal calcium one month later, compared with 56% guided by MIBI. FCH PET/CT also detects multiple abnormal glands far better than MIBI, reducing the chance that a missed gland causes a second operation.

### Is FCH PET/CT safe in terms of radiation exposure?

FCH PET/CT involves radiation, but a single scan means lower cumulative radiation than having both MIBI and FCH scans sequentially. The FCH tracer has been used in Europe for over 20 years. Your care team will consider the benefits of accurate localization against the small radiation risk.

### Who should get an FCH PET/CT scan?

The evidence supports FCH PET/CT as a first-line imaging option for all types of hyperparathyroidism when surgery is planned. It is especially recommended for renal (secondary) hyperparathyroidism, hereditary conditions like MEN1, and patients with persistent or recurrent disease after prior surgery.

### Does FCH PET/CT still work after a failed parathyroidectomy?

Yes. In patients with suspected persistence or recurrence, FCH PET/CT was positive in 78% of cases, nearly the same as in patients without prior surgery (84%). It also outperformed 4D-CT in this setting, making it a valuable tool before repeat surgery, which carries higher risk.

### Is FCH PET/CT worth the extra cost compared with other scans?

Although FCH PET/CT costs more per dose than MIBI, studies in the US and Dutch healthcare systems found it cost-effective. In a US model, FCH PET/CT gained the most quality-adjusted life-years and MIBI was less effective and more costly overall. Better accuracy can prevent failed surgeries and repeat procedures.

## Source Information

**Original article title:** 18F-Fluorocholine-Positron Emission

**Authors:** Lucia Noskovicova, Sona Balogova, Cyrielle Aveline, Marc Tassart, Jules Zhang-Yin, Khaldoun Kerrou, Ivan Jaksic, Françoise Montravers, Jean-Noël Talbot

**Journal:** Seminars in Nuclear Medicine (2024, in press). DOI: 10.1053/j.semnuclmed.2024.08.002

**Affiliations:** Departments of Nuclear Medicine at Comenius University Bratislava / St. Elisabeth Oncology Institute and Bory Hospital, Slovakia; Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, France; Clinique Sud Luxembourg, Belgium; and Institut National des Sciences et Techniques Nucléaires (INSTN), Saclay, France.

**Note:** This patient-friendly article is based on peer-reviewed research. It has been written in plain language while preserving the key data and findings from the original publication. It is intended for educational purposes and is not a substitute for individualized medical advice from your healthcare team.


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