Whole-body dynamic FDG-PET/CT Parametric Imaging in Alveolar Echinococcosis

doi:10.21203/rs.3.rs-6907316/v1

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Whole-body dynamic FDG-PET/CT Parametric Imaging in Alveolar Echinococcosis

https://doi.org/10.21203/rs.3.rs-6907316/v1

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Journal Publication

published 06 Oct, 2025

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Objective

To determine the role of whole-body dynamic (WBD) / Patlak parametric ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with alveolar echinococcosis (AE). This technique allows separating metabolized from unmetabolized FDG in the blood pool and tissue, potentially providing complementary qualitative information and superior quantification to standard static PET/CT images.

Methods

We prospectively analysed 20 PET/CT datasets performed for staging or therapy monitoring in patients with confirmed AE. Dynamic and standard static PET/CT datasets were acquired in all patients, and quantitative imaging parameters were measured in the lesion with the highest uptake (i.e., maximum standardized uptake value (SUVmax) and Patlak parameters) and compared to normal liver tissue (SUVratio and Patlak ratio).

Results

Mean SUVmax in AE manifestations was 5.7 ± 3.1 (3.2–13.9), compared to 3.2 ± 0.4 (2.5–4.2) in non-infected liver tissue, respective values for Patlak were 13.0 ± 8.6 (2.7–35.5) and 4.9 ± 2.8 (0.6–12.1). SUVratio (1.8 ± 1.1; 1.0-5.2) was significantly lower (P < 0.001) than Patlak ratio (3.2 ± 3.2; 1.1–15.6). Both ratios correlated significantly with E. granulosus hydatid fluid (EgHF) antibodies (SUVratio r = 0.73, P < 0.001; Patlak ratio r = 0.85, P < 0.001).

Conclusions

WBD PET/CT yields higher lesion-to-background contrast and may therefore have the potential to increase sensitivity in the assessment of hepatic AE.

PET/CT

FDG

dynamic PET

Patlak analysis

parametric imaging

alveolar echinococcosis

Alveolar echinococcosis (AE) is a rare zoonotic parasitosis [1] that typically manifests as a slow-growing tumor-like liver lesion. Advances in treatment have significantly improved patient prognosis. Complete surgical resection offers a potential cure [2, 3], while in advanced or inoperable cases, benzimidazole therapy has been shown to effectively control the disease and substantially enhance patient outcomes [4–9]. However, certain aspects of AE management remain without expert consensus or strong evidence, including: i) the optimal imaging modality for disease staging, ii) the management of patients experiencing significant morbidity due to benzimidazole therapy side effects, iii) the discontinuation of “lifelong” benzimidazole therapy, as evidence suggests that treatment may have parasitocidal effects, allowing for safe termination in select cases [10, 11].

A main challenge in AE management includes the inability to directly assess parasite vitality. Instead it is indirectly derived from parameters quantifying the host’s immune response, including anti-Em18 serology and perilesional metabolic activity on FDG-PET/CT imaging [10, 11]. These parameters, however, suffer from certain limitations. Anti-Em18 serology in the real-world setting and perilesional metabolic activity determined by FDG-PET/CT suffer from low sensitivity, the latter demonstrated by variable measurement outcomes over time and more frequent detection of residual activity in delayed imaging [12, 13]. Treated AE lesions typically show only faint FDG uptake, which is further obscured by the relatively high liver background, making their assessment challenging with standard static PET/CT.

A recently introduced PET/CT imaging technique, known as whole-body dynamic (WBD) PET/CT (or Patlak parametric imaging), enables differentiation between metabolized FDG and unmetabolized FDG in the blood pool and tissue [14, 15]. This technique may enhance lesion-to-background contrast, potentially improving the sensitivity and accuracy of PET/CT for staging and therapy monitoring in hepatic AE [16].

Thus, our study aimed to evaluate the role of WBD / Patlak parametric PET/CT in patients with AE.

Study design and data collection

This prospective study analysed 20 PET/CT scans from patients with confirmed AE, who were referred for staging or therapy monitoring between 2022 and 2024 at the ***anonymized for review***. Relevant clinical data, including patient demographics, laboratory results, and clinical and treatment information, were collected at the time of PET/CT.

The study protocol was approved by the local ethics committee (BASEC-Nr. 2022 − 01493) and all patients provided written informed consent. All procedures were conducted in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Imaging data acquisition

Patients fasted for at least four hours, and body weight, height, and blood glucose level were measured prior to the examination. FDG dosage was body-weight adjusted and injected on the scanner bed (6-ring Discovery MI Gen2, GE Healthcare). Dynamic and standard static PET/CT data sets were acquired in all patients. Dynamic imaging started either directly after injection, with a single bed covering the heart being acquired for 10 minutes (12x5seconds, 4x10seconds, 8x25seconds, 5x60seconds), followed by 11 whole-body dynamic frames over 46minutes (5 beds, 50 seconds/bed), or following an initial uptake time of 26 minutes followed by 7 frames over 29 minutes. Following the end of the dynamic acquisition, a static acquisition at 60 minutes post-injection (1.5 minutes/bed) was then performed. Reconstructed images, along with an aortic input function (IF), were used to generate MR_FDG images (DynamicIQ; GEHealthCare), based on traditional Patlak analysis (11 frames, full IF) and relative Patlak analysis (7 frames, partial IF). The input function was corrected for blood to plasma partition and fitted with a bi-exponential model while preserving the area under the curve for the first 10 min where continuous sampling was available in standard Patlak analysis. Standard static PET/CT imaging was performed at 60 minutes post-injection, without changing the position of the patient in the arms-down position. A non-enhanced CT scan was used for attenuation correction.

Data analysis and definitions

Quantitative imaging parameters were measured in the lesions exhibiting the highest FDG uptake (i.e., maximum standardized uptake value (SUVmax) as well as MR_FDG), and compared to normal/non-infected liver tissue (SUVratio and Patlak ratio). In line with a commonly used approach for assessing hepatic background - such as in lymphoma evaluation - we utilized SUVmax as the reference parameter [17]. Measurements were performed by two experienced, doubly board certified nuclear medicine physicians and radiologists using a dedicated workstation (Advantage Workstation, Version 4.7; GE HealthCare Biosciences, Pittsburgh, PA). In case of discrepancy, the data was reanalysed by both readers, and a consensus was reached.

Additionally, the readers quantified the number of detectable hepatic and extrahepatic lesions, as well as the size of the largest liver lesion. Disease extent was staged according to the. PNM classification (P = parasitic mass in the liver; N = involvement of neighboring organs; M = metastasis) as defined by the WHO Informal Working Group on Echinococcosis [2, 18–20]. The presence of calcifications within AE manifestations was categaorized as none, mild, intermediate or extensive.

Finally, serum samples, taken at the time of the PET/CT, were analyzed at the Institute of Parasitology, University of Zurich, using Em-18 antigens. Enzyme-linked immunosorbent assays (ELISA) for E. granulosus hydatid fluid (EgHF) were carried out as previously described by Kronenberg et. al [21].

Statistical analyses

Statistical analyses were conducted using commercially available software (IBM SPSS Statistics, Version 30). Quantitative variables were reported as mean ± standard deviation (range), while categorical variables were reported as frequencies and percentages. Differences in SUVratio and MR_FDG ratio in AE manifestations were tested for significance using Mann-Whitney-U-test. Pearson correlation coefficients were calculated to compare absolute values of SUVratio and MR_FDG ratio with EgHF antibodies. A p-value of ≤ 0.05 was considered to indicate statistical significance.

Patient population

PET/CT was performed in 20 patients with serology-confirmed alveolar echinococcosis for staging and assessment of metabolic activity at baseline (n = 7) or restaging or as part of a structured treatment discontinuation (n = 13). The mean age of the patients was 52 ± 17 years (range: 22–80), with a mean weight of 70 ± 12 kg (range: 52–95) and a mean height of 172 ± 7 cm (range: 160–188). Sixty percent (n = 12) of the patients were female. None of the patients had elevated blood glucose levels prior to the PET/CT examination (mean4.9 mmol/L (range: 4.7–6.7). A mean dose of 174 ± 61 MBq FDG (range: 103–302) was administered. The demographics of the patient population are given in Table 1.

Table 1

Patient demographics of all patients.
ID	Age	Gender	Weight in kg	Height in cm	PNM	Days between initial diagnosis and PET/CT	Number of lesions	Size of biggest lesion (mm)	Calcifications	Em-18 in AU	EgHF in AU	SUVmax	Patlak	SUV ratio	Patlak ratio
01	36	female	61	167	P1N0M0	61	5	42	mild	0	27	3.2	5.3	1.0	1.1
02	80	male	89	177	P4N1M1	21	1	125	intermediate	42	31	9.4	18.5	2.9	4.0
03	56	female	58	169	P2N0M0	121	2	32	mild	0	0	3.4	11.4	1.1	1.7
04	43	female	58	165	P4N0M0	1181	7	37	extensive	0	3	3.2	12.8	1.0	1.1
05	71	male	76	172	P4N0M0	3963	1	95	extensive	1	16	5.2	11.7	1.5	2.7
06	55	female	65	170	P4N1M0	5034	3	92	extensive	42	59	11.2	43.3	2.7	4.3
07	77	female	54	167	P4N1M0	2087	> 20	56	extensive	1	41	3.5	22.3	1.1	2.3
08	75	female	60	160	P4N0M0	3240	2	102	extensive	0	12	5.3	18.8	1.5	1.5
09	60	male	90	188	P4N1M0	4004	2	61	intermediate	18	27	7.3	28.8	2.5	4.2
10	26	female	52	164	P2N0M0	10	1	58	intermediate	5	28	4.1	15.7	1.3	2.6
11	40	female	78	176	P4N1M0	2318	1	105	intermediate	0	25	4.2	5.9	1.3	1.9
12	35	male	70	186	P2N0M0	851	1	95	extensive	0	20	3.5	8.3	1.1	2.1
13	39	female	75	166	P4N0M0	3110	1	53	extensive	1	8	3.9	5.2	1.0	2.0
14	22	female	65	168	P2N1M0	255	1	129	extensive	n.a.	n.a.	9.1	2.7	2.5	4.6
15	58	male	86	182	P2N1M0	2318	2	58	intermediate	4	11	3.9	6.1	1.3	2.0
16	65	male	69	173	P2N1M0	41	2	85	mild	108	19	8.6	18.0	3.4	5.2
17	71	male	62	178	P2N0M0	1443	2	57	intermediate	0	10	4.0	6.2	1.3	1.6
18	49	male	70	168	P3N0M0	29	1	95	intermediate	0	106	13.9	22.2	5.2	15.6
19	54	female	95	175	P1N0M0	55	1	67	extensive	2	46	4.2	11.2	1.2	2.8
20	35	female	59	174	P4N0M0	1911	2	16	mild	0	1	3.2	4.8	1.1	1.6

Abbreviations: AU: antibody units; CT, computed tomography; EgHF: E. granulosus hydatid fluid; Em-18: levels of Em-18 antibodies; FDG: ¹⁸F-fluorodeoxyglucose; ID: Patient identification; n.a.: not applicable; PNM (PNM stage: P = parasitic mass in the liver, N = involvement of neighboring organs, M = metastasis); SUVmax: maximum standardized uptake value.

At the time of the PET/CT examination, 16 patients (80%) were undergoing benzimidazole therapy. In three of the patients not on benzimidazole therapy, treatment was initiated after the PET/CT, while in one patient treatment was stopped just prior to the PET/CT and has not been reinitiated since.

PET/CT

PET/CT was successfully performed with diagnostic image quality after intravenous injection of FDG in all patients (Figs. 1 and 2). The mean SUVmax in AE manifestations with the highest FDG-uptake was 5.7 ± 3.1 (range: 3.2–13.9), compared to 3.2 ± 0.4 (range: 2.5–4.2) in non-infected liver tissue. Respective values for Patlak were 13.0 ± 8.6 (range: 2.7–35.5) and 4.9 ± 2.8 (range: 0.6–12.1) for MR_FDG. The SUVratio (1.8 ± 1.1; range 1.0-5.2) was significantly lower (P < 0.001) than the MR_FDG ratio (3.2 ± 3.2; range 1.1–15.6). All individual values are presented in Table 1.

Relation of quantitative PET/CT measurements and antibodies

The mean serum EgHF antibody units (AU) were 28.8 ± 24.3 (range 0.0-106), while the respective values for EgP were 29.8 ± 27.6 (range 0.0-103), and for Em-18 11.8 ± 26.1 (0.0-108.X); individual values are displayed in Table 1.

Ratios of metabolic activity of the AE manifestation measured in PET/CT were significantly correlated with serum EgHF AU levels (SUVratio r = 0.73, P < 0.001; Patlak ratio r = 0.85, P < 0.001). However, no correlation of any PET ratio parameter and Em-18 was found (P = n.s.).

We analysed the role of whole-body dynamic / Patlak parametric PET/CT imaging in patients with AE. Our study results are as follows: (i) WBD PET/CT images provide higher lesion-to-background contrast compared to standard static PET/CT images. (ii) The lesion-to-background contrast for both imaging techniques correlates significantly with serum EgHF antibodies.

Although PET/CT has been demonstrated as a reliable modality for staging, restaging, and therapeutic decision-making in patients with AE [22], serological markers (such as EM-18) are currently preferred over PET/CT in clinical practice. These markers typically offer comparable clinical information at lower cost and without radiation exposure. PET/CT is currently mainly utilized for two specific indications: (i) patients with active disease but negative EM-18 serology, and (ii) patients for in whom long-term benzimidazole treatment is being considered for discontinuation.

EM-18 antibody is a highly specific marker for active infection and serves as the most important marker for diagnosis and therapy monitoring in AE [23, 24]. In a small subset of patients, EM-18 serology may occasionally be negative despite the presence of active AE. In these cases, PET/CT is routinely employed for staging and therapy monitoring. Our results demonstrate that both imaging techniques demonstrate excellent correlation with EgHF antibodies, and that WBD PET/CT images provide higher lesion-to-background contrast compared to standard PET/CT images. Based on these findings, we hypothesize that the sensitivity and accuracy for staging and therapy monitoring may be further improved with this the new technique. However, this hypothesis was beyond the scope of our current study and warrants further investigations.

In patients with inoperable AE, long-term benzimidazole treatment may be considered for discontinuation, as aborted forms of AE have been observed after years of therapy, suggesting that benzimidazole may be parasitocidal and not just parasitostatic in some cases [6]. Initial attempts to discontinue benzimidazole therapy based on negative PET/CT follow-up scans,regardless of serology markers, were associated with a high rate of recurrence [12]. We may hypothesize that the potentially higher sensitivity of WBD PET/CT could reduce the recurrence rate in a similar study setting. In current clinical practice, the decision to discontinue benzimidazole therapy is usually based on a combination of negative PET/CT results and undetectable levels of Em-18 antibodies, a strategy that has been shown to be sucessful without recurrences in smaller study polpulations [25]. However, it is important to note that the introduction of WBD PET/CT may potentially jeopardize the success of benzimidazole therapy discontinuation. An increase in sensitivity with WBD PET/CT imaging may, in fact, represent a post-hoc fallacy, leading to an unnecessary prolongation of benzimidazole therapy in some patients.

We performed both full dynamic acquisition with injection on the table followed by analysis with standard Patlak as well as truncated dynamic acquisitions resulting in a partial input function followed by analysis with relative Patlak. A full dynamic acquisition for 60min even though could provide superior quantification to standard SUV values, is a time consuming alternative to standard static imaging or serological markers. Relative Patlak can provide indistinguishable lesion-to-background contrast compared to standard Patlak as the scaling in the MR_FDG resulting from the truncated input function, cancels out in the ratio. Hence relative Patlak analysis from a short dynamic acquisition, could potentially substitute static acquisition metrics in the future, as the duration of such truncated dynamic scans could become similar to current static acquisitions when acquired on longer axial FOV scanner of increased sensitivity.

Limitations of the study

Our present prospective study involved a relatively small number of patients, given the rarity of the disease. Additionally, the study population was heterogeneous, including patients referred for initial staging and for following-up of AE, as well as a high number of patients with negative Em-18 marker, which limited the ability to draw conclusive statistical conclusions. However, despite these limitations, we were able to statistically confirm the hypothesis that WBD PET/CT demonstrated higher lesion-to-background contrast in patients with AE.

WBD PET/CT provides significantly higher lesion-to-background contrast compared to standard static PET/CT and may therefore enhance sensitivity and accuracy in the assessment and reassessment of hepatic AE.

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Journal Publication

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You are reading this latest preprint version

Whole-body dynamic FDG-PET/CT Parametric Imaging in Alveolar Echinococcosis

Status:

Journal Publication

Version 1

Abstract

Objective

Methods

Results

Conclusions

Figures

Introduction

Methods

Study design and data collection

Imaging data acquisition

Data analysis and definitions

Statistical analyses

Results

Patient population

PET/CT

Relation of quantitative PET/CT measurements and antibodies

Discussion

Limitations of the study

Conclusion

References

Status:

Journal Publication

Version 1