1 Measuring diffuse metabolic activity on FDG-PET/CT: new
2 method for evaluating Langerhans cell histiocytosis activity in
3 pulmonary parenchyma☆
4 PetrQ1 Szturza,⁎, Zdeněk Řehákb
, Renata Koukalováb
, Zdeněk Adama
, Marta Krejčía
,
5 Luděk Poura
, Lenka Zahradováa
, Jiří Vaníčekc
, Tomáš Nebeskýd
, Roman Hájeka
, Jiří Mayera
6
a
Department of Internal Medicine–Hematooncology, Faculty of Medicine of Masaryk University and University Hospital Brno, Czech Republic
7
b
Department of Nuclear Medicine, PET Centre at the Masaryk Memorial Cancer Institute, Brno, Czech Republic
8
c
Department of Imaging Methods, Faculty of Medicine of Masaryk University and St. Anne's University Hospital Brno, Czech Republic
9
d
Radiological Clinic, Faculty of Medicine of Masaryk University and University Hospital Brno, Czech Republic
10 Received 6 June 2011; received in revised form 23 August 2011; accepted 4 October 2011
11 Abstract
12 Introduction: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cause of interstitial lung disease characterized by formation of
13 nodules in the active phase of the disease that evolve into nonactive cystic lesions later on. To evaluate PLCH activity in patients, we
14 developed a new method for measuring diffuse metabolic activity on fluorine-18-fluorodeoxyglucose positron emission tomography/
15 computed tomography (FDG-PET/CT) using a lung-to-liver activity ratio.
16 Material and Methods: We retrospectively studied a series of 4 FDG-PET and 23 FDG-PET/CT scans from 7 patients with PLCH and
17 analyzed a sample of 100 randomly chosen FDG-PET/CT studies free from any known lung or hepatic diseases. Maximum standardized
18 uptake value (SUVmax) in a spherical volume (6–8 cm in diameter) in the right lung was put into relation with SUVmax in a spherical
19 volume (9–10 cm in diameter) in the reference liver parenchyma to set up the SUVmaxPULMO/SUVmaxHEPAR index. The index values
20 were compared to the disease course in each patient.
21 Results: In patients with PLCH, a close correlation between the index value and the disease course was found in all seven subjects, where the
22 increasing index values indicated disease activity, while decreasing index values were observed after therapy administration. In the group of
23 100 healthy control subjects, we found index values lower than 0.3 in 80% and lower than 0.4 in 96% [range: 0.14–0.43; 0.24±0.07 (100)].
24 Conclusion: Measuring SUVmaxPULMO/SUVmaxHEPAR values and their time-trend monitoring represent simple, noninvasive screening
25 tools allowing an early diagnosis and treatment response follow-up assessment in patients with PLCH.
26 © 2011 Published by Elsevier Inc.
27
28 Keywords: Langerhans cell histiocytosis; Interstitial lung disease; Positron emission tomography; Pulmonary function tests; High-resolution computed
29 tomography (HRCT)
30
31 1. Introduction
32 Pulmonary Langerhans cell histiocytosis (PLCH) is a rare
33 condition, the symptoms of which are nonspecific and
34include cough, chest pains and dyspnea, and sometimes,
35even pneumothorax may be its first manifestation. In the
36early stages of the disease, small nodules evolving through
37cavitated forms into thick-walled, later thin-walled and
38eventually confluent cysts, and start to build up in pulmonary
39parenchyma. These changes predominantly affect upper lung
40zones with relative sparing of the lung bases [1]. Radiolog-
41ical appearance of advanced PLCH on conventional
42radiographs or even high-resolution computed tomography
43(HRCT) scans may be difficult to distinguish from
44emphysema, which often leads to delays in getting the
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☆
Conflict of interest: The authors declare that they have no conflict of
interest.
⁎ Corresponding author. Department of Internal Medicine-Hematooncology,
University Hospital Brno, Jihlavská 20, 625 00 Brno, Czech
Republic. Tel.: +42 0532233064; fax: +42 0532233603.
E-mail address: petr.szturz@fnbrno.cz (P. Szturz).
0969-8051/$ – see front matter © 2011 Published by Elsevier Inc.
doi:10.1016/j.nucmedbio.2011.10.002
NMB-07094; No of Pages 8
45 right diagnosis and initiating proper treatment. In addition,
46 X-ray findings are sometimes inconclusive without any
47 correlation to serious clinical symptoms (Fig. 1).
48 Langerhans cell histiocytosis limited only to pulmonary
49 parenchyma is a smoke-related interstitial lung disease
50 referred to as isolated PLCH, and it has a better prognosis
51 than Langerhans cell histiocytosis with multisystemic
52 involvement including lungs. Although having different
53 prognoses and therapeutic approaches, these two entities
54 present the same clinical, radiological and histopathological
55 manifestations [2,3]. PLCH is responsible for 3%–5.5% of
56 interstitial lung diseases [4–6]. Larger epidemiologic data
57 are available from Japan [7], where the estimated crude
58 prevalences in males and females are 0.27 and 0.07 per
59 100,000 population, respectively. Most patients with PLCH
60 are young cigarette smokers between 20 and 40 years of
61 age [1].
62 Diagnostics include surgical lung biopsy and bronchoal-
63 veolar lavage with CD1a+ elements (Langerhans cells)
64 analysis [8]. Additionally, in the setting of multisystemic
65 Langerhans cell histiocytosis, characteristic HRCT scan
66 findings in the lungs may be sufficient for the diagnosis.
67 Treatment is indicated in patients with multisystem involve-
68 ment or when a progression of pulmonary lesions has been
69confirmed. The progression is characterized by increasing
70numbers of nodules, whereas formation and enlargement of
71cysts are only a natural disease development into its terminal,
72end-stage phase. HRCT scans and pulmonary function tests
73are routinely applied in the follow-up; however, determining
74the number of nodules on HRCT scans is extremely difficult
75and time consuming, and pulmonary function tests cannot
76always distinguish between end-stage cystic disease and
77active PLCH [6,9].
78To facilitate the PLCH activity assessment, we developed
79and verified a new method for measuring diffuse metabolic
80activity on fluorine-18-fluorodeoxyglucose (FDG) positron
81emission tomography/computed tomography (PET/CT) scan
82imaging using the SUVmaxPULMO/SUVmaxHEPAR
83index. In this paper, we describe this methodology and
84verify its validity on a retrospective study of a PLCH
85patient cohort.
862. Materials and methods
872.1. Patients
88During a 21-year period from November 1, 1989, to
89January 1, 2011, 23 patients were diagnosed with Langerhans
Fig. 1. Different radiological imaging modalities of the chest in a patient with multisystemic Langerhans cell histiocytosis with pulmonary involvement (female,
born 1955). The patient presenting with fevers and dyspnea was admitted to hospital with suspected pneumonia in July 2010. There were no abnormalities seen
on conventional radiography (1), in contrast to HRCT imaging (3 and 4) showing apart from hypostatic pneumonia also diffuse small cysts (4–15 mm in size) in
both lung fields resembling emphysema, which was visualized using 3D reconstruction (2). Cystic lung disease, complicated by bacterial infection, was an
accidental finding in this patient. However, retrospective analysis of the SUVmaxPULMO/SUVmaxHEPAR index in preceding four PET examinations (2004–
2010) shows a high probability of a previous history of PLCH (Table 2).
2 P. Szturz et al. / Nuclear Medicine and Biology xx (2011) xxx–xxx
90 cell histiocytosis and followed up at our department. Out of
91 them, 15 patients had either single-systemic (nine patients)
92 or multisystemic (six patients) disease without pulmonary
93 involvement. The remaining eight patients were diagnosed
94 with PLCH, of whom seven underwent FDG-PET scan
95 imaging. In total, 4 FDG-PET and 23 FDG-PET/CT studies
96 were performed between the years 2004 and 2010. The study
97 follow-up period started with the first FDG-PET examination
98 in March 2004.
99 The indications for FDG-PET or FDG-PET/CT scanning
100 included: (a) searching for multiorgan involvement of an
101 extrapulmonary (verified by bone, lymph node or skin
102 biopsies) Langerhans cell histiocytosis (four scans) as well as
103 (b) of known PLCH (two scans), (c) differential diagnosis of
104 pituitary stalk infiltration (one scan) and (d) follow-up of
105 patients (20 scans). The patients were free from any other
106 active lung or liver disease at the time of PET scanning. The
107 diagnosis of PLCH was based on pathological examinations
108 (three patients) or pathognomonic HRCT scan findings (four
109 patients). Patients who did not agree to the use of their
110 medical records for research were not included in this study.
111 2.2. FDG-PET/CT scan imaging
112 In the PLCH patient cohort, we performed FDG-PET and
113 FDG-PET/CT scanning in euglycemia after fasting for 6 h.
114 FDG-PET scan images of the body, at the extent from the
115 proximal thirds of femurs to the cranial base (with included
116the head in four scans), were obtained 60 min after
117intravenous injection of fluorodeoxyglucose (range of
118applied activity: 312–409 MBq). Until 2008, data acquisi-
119tion was performed on a PET scanner (ECAT ACCEL
120SIEMENS) in a three-dimensional (3D) mode and, later,
121from 2008, on a hybrid PET/CT scanner (True Point PET-CT
122Biograph 64 SIEMENS). Emission and transmission scans
123were reconstructed by using an iterative reconstruction
124algorithm. On acquired data, attenuation correction was
125applied. Due to repeated follow-up FDG-PET/CT scanning,
126in most studies, low-dose CT protocol reducing radiation
127load significantly was used. With the remaining studies,
128high-dose CT mode was applied. The scan field of view was
12950 or 70 cm according to a patient's body habitus. The
130acquisition parameters for CT were as follows: slice 5 mm,
131collimation 24×1.2 mm, pitch 0.8 mm. To optimize lung
132parenchyma imaging, the following reconstruction algorithm
133was used: slice 1.5–2.0 mm, kernel B 80 f (ultra sharp),
134reconstruction increment 0.4 mm, window–lung. Maximum
135standardized uptake values (SUVmax) were measured for
136semiquantitative analysis.
1372.3. SUVmaxPULMO/SUVmaxHEPAR index
138Nodules in PLCH often measure several millimeters (4–6
139mm) and are below detectable levels of used PET scanners
140(about 7 mm), which precludes direct measurement of their
141activity. Therefore, we tried to find these active lesions in a
Fig. 2. SUVmax in a spherical volume (6–8 cm in diameter) in the right lung was put into relation with SUVmax in a spherical volume (9–10 cm in diameter) in
the reference liver parenchyma to set up the SUVmaxPULMO/SUVmaxHEPAR index. Considering the topographical differences between the lungs and the
liver, we were more limited in demarcating the volume of interest in the lung parenchyma, which therefore has smaller diameter.
3P. Szturz et al. / Nuclear Medicine and Biology xx (2011) xxx–xxx
142 larger area. Considering the anatomical conditions, we chose
143 the volume of interest shaped into spheres of 6–8 cm in
144 diameter in the right lung. The metabolic activity was
145 measured in the right upper and middle lung fields. These are
146 the regions of predominant PLCH involvement. The right
147 side without heart and pericardium is more suitable for
148 demarcating the volume of interest and requires only the
149 exclusion of the hilar structures and pleura, where the
150 activity can be increased physiologically. Moreover, in the
151 lower lung fields, numerous motion artifacts are common.
152 This selection of size and location of the volume of interest
153 strives to maximize the probability of occurrence of the
154 majority of active lesions in the most anatomically suitable
155 region while preserving an easy way of determination in a
156 daily routine.
157 To decrease the variability between single examinations
158 as well as to compare examinations from different scanners,
159 lung-to-liver activity ratio was assessed. In the liver
160 parenchyma, we chose volume of interest shaped into
161 spheres of 9–10 cm in diameter following analogous
162 principles as in the lungs (Fig. 2). Consequently, SUVmax
163 in the right lung and SUVmax in the reference hepatic
164parenchyma were measured, and their relationship expressed
165as the SUVmaxPULMO/SUVmaxHEPAR index was deter-
166mined and used for PLCH activity evaluation.
167In our analysis of a sample of 100 randomly chosen
168FDG-PET/CT studies free from any known lung or
169hepatic diseases, either oncological or nononcological, we
170found index values lower than 0.3 in 80% and lower than
1710.4 in 96% [range: 0.14–0.43; 0.24±0.07 (100)]. No index
172values higher than 0.5 were identified in the healthy
173population. The range of applied activity was 302–425
174MBq [354.51±32.12 (100)], and that of blood glucose levels
175was 3.1–8.1 mmol/L [5.00±1.09 (100)]. Further SUV data
176are summarized in Fig. 3.
1773. Results
178Six males, all with a history of smoking, and one female,
17931 to 48 years of age at the time of first FDG-PET scanning
180[39.7±6.5 (7)], were included in this study. The mean follow-
181up period was 17 months [range: 9–79 months; 30.4±29.0
182(7)]. Six patients had a multisystemic Langerhans cell
183histiocytosis with pulmonary involvement and received at
184least one line of therapy. One patient had isolated PLCH, and
185this patient has not been treated yet. In patients with
186multisystemic disease, the following organs were affected:
187lungs (100%), skin (65%), bones (50%), brain (30%), ear
188(30%) and lymph nodes (15%). Respiratory symptoms
189(dyspnea, cough) were present in five patients (71%), of
190whom one patient suffered from recurrent pneumothorax.
191Demographic and clinical data are shown in Tables 1 and 2.
192All patients underwent FDG-PET scan imaging (4 PET
193scans and 23 PET/CT scans). The acquired data, summarized
194in Table 3, were correlated to the clinical course of the
195disease, HRCT findings, pulmonary function tests and
196pathological examinations. In total, 18 HRCT studies
197[2.6±1.3 (7)] and 13 pulmonary function tests [1.9±1.5 (7)]
198were performed in seven patients. We have found a close
199correlation between the SUVmaxPULMO/SUVmaxHEPAR
200index values and the above-mentioned disease activity
201parameters (Table 2). Consequently, we worked with two
202variables, the index value and the metabolic tumor activity,
203and found a relationship with positive slope, i.e., increasing
204index value corresponds with increasing metabolic tumor
Fig. 3. Box plot of SUV data of control group: median SUVmaxPULMO=
0.70 [range: 0.380–1.600; 0.74±0.26 (100)], median SUVmaxHEPAR=
3.00 [range: 2.40–4.00; 3.11±0.35 (100)], median SUVmaxPULMO/
SUVmaxHEPAR=0.22 [range: 0.14–0.43; 0.24±0.07 (100)].
Table 1t1:1
Main demographic and clinical characteristics of seven patients with PLCHt1:2
t1:3 Date of birth, sex Smoking habitus Disease
onset (years)
Extrapulmonary involvement Diagnosis of pulmonary
involvement (years)
t1:4 1972, M Smoker 21 Bones 34
t1:5 1974, M Smoker 33 Skin, brain (pituitary stalk), ear 34
t1:6 1969, M Ex-smoker 39 Skin 40
t1:7 1963, M Active and passive smoker 43 Ear 45
t1:8 1973, M Smoker 34 Skin, bones, lymph nodes 35
t1:9 1963, M Smoker 45 Isolated PLCH 45
t1:10 1955, F Nonsmoker 22 Skin, bones, brain, ear 54
4 P. Szturz et al. / Nuclear Medicine and Biology xx (2011) xxx–xxx
205 activity and vice versa. The increasing trends of index
206 values were seen in five patients, where they indicated
207 PLCH activity (i.e., pulmonary symptoms, formation of
208 nodules on HRCT or abnormal pulmonary function tests),
209 whereas decreasing trends of index values were observed in
210 six patients after therapy administration, signaling reduced
211 metabolic tumor activity. Furthermore, in four patients,
212 SUVmaxPULMO/SUVmaxHEPAR index values higher
213 than 0.5 proved to be diagnostic for pulmonary involve-
214 ment, demonstrating its role as a strong positive predictive
215 marker. Fig. 4 shows the disease course with corresponding
216 index values in one patient (male, born 1973).
217 Quantitative analysis of HRCT findings in patients with
218 PLCH, consisting of assessment of the exact count of
219nodules and cystic formations, is almost impossible to be
220obtained. Therefore, the PET-CT findings were correlated to
221a semiquantitative radiological evaluation of HRCT scans,
222and neither sensitivity, specificity, accuracy nor predictive
223values can be exactly calculated in our study.
2244. Discussion
225The clinical course of PLCH is very divergent and
226impossible to be predicted for an individual patient [2,3].
227About 50% of patients with isolated PLCH have a favorable
228prognosis with total disease remission, i.e., reduction of
229pulmonary nodules either spontaneously or after corticoid
Table 2t2:1
Correlation between the SUVmaxPULMO/SUVmaxHEPAR index and disease course in seven patients with PLCHt2:2
t2:3 Date of
birth, sex
Date of
PET-CTa
SUVmax
PULMO/SUVmax
HEPAR
Disease course and symptoms of
pulmonary involvement
Interpretation of SUVmaxPULMO/SUVmaxHEPAR
index in relation to disease course
t2:4 1972, M Mar 04 0.44 After 5 cycles of cladribine therapy, remission
of bone lesions
High index value due to active smoking
t2:5 Jan 05 0.45 Lasting remission of bone lesions
t2:6 Feb 07 0.51 Dyspnea, cough Progression of PLCH
t2:7 Jun 08 0.47 Smoking cessation leading to relief of symptoms Gradual remission of PLCH in accordance with
relief of symptoms after cessation of smoking
t2:8 Jan 09 0.29
t2:9 Feb 10 0.27
t2:10 1974, M Mar 09 0.21 Screening admission PET/CT
t2:11 Feb 10 0.27 Progression of pituitary stalk infiltration on
brain MRI; therapy initiation
Increased index value suggests progression in lungs
t2:12 Jun 10 0.22 Regression of pituitary stalk infiltration
after 3 cycles with cladribine
Therapy effective also in PLCH as suggested by
decreasing index value
t2:13 1969, M May 09 0.57 Disease activity (recurrent pneumothorax, 3 times);
therapy initiation
High index value confirms PLCH
t2:14 Mar 10 0.22 After 6 cycles of cladribine therapy, partial
remission of skin lesions
Therapy effective in PLCH as suggested by
decreasing index value
t2:15 1963, M Mar 09 0.57 Screening admission PET/CT High index value confirms PLCH
t2:16 Aug 09 0.53 After 4 cycles of cladribine therapy Gradual remission of PLCH after successful
cladribine therapy
t2:17 Mar 10 0.38 Follow-up PET/CT
t2:18 1973, M Jan 09 0.54 Screening admission PET/CT; dyspnea, cough High index value confirms PLCH
t2:19 Jun 09 0.31 After 4 cycles with cladribine therapy Therapy effective also in PLCH
t2:20 Nov 09 0.36 1st relapse (confirmed by lymph node and
skin biopsies); cough
Increased index value suggests relapse in lungs
t2:21 Jan 10 0.27 After 2 cycles of salvage chemotherapy CHOEP;
relief of symptoms
Remission of PLCH after chemotherapy
t2:22 Jul 10 0.28 4 months after autologous transplantation Lasting remission of PLCH after
autologous transplantation
t2:23 Oct 10 0.48 2nd relapse (confirmed by lymph node biopsy) Increased index value suggests 2nd relapse in lungs
t2:24 1963, M Jul 08 0.21 Screening admission PET/CT; intermittent cough
t2:25 Feb 10 0.24 Stable disease not requiring therapy;
lasting intermittent cough
Slightly increased index value in patient with stable
clinical manifestation, but still continuing his
smoking habitus
t2:26 1955, F Mar 04 0.42 Screening admission PET/CT; slight effort dyspnea High index value suggests pulmonary involvement
t2:27 Jan 09 0.31 After several cycles with vinblastine,
prednisone and etoposide
Therapy effective also in PLCH
t2:28 Mar 10 0.14 Progression in brain; therapy initiation Further remission of PLCH
t2:29 May 10 0.17 After 2 cycles with cladribine Lasting remission of PLCH
t2:30 Oct 10 0.38 Further progression in brain, chemoresistant disease Increased index suggests progression of PLCH
CHOEP, cyclophosphamide+doxorubicin+vincristine+etoposide+prednisone.t2:31
a
Between 2004 and 2007, only PET scans were made.t2:32
5P. Szturz et al. / Nuclear Medicine and Biology xx (2011) xxx–xxx
230 therapy. Cessation of smoking proved to be essential in
231 therapy management, leading to remission in many cases
232 described [6,10,11]. Nevertheless, cystic lung damage is
233 irreversible. Moreover, PLCH implies a higher risk of lung
234 cancer, especially in smokers, and a higher risk of other
235 malignancies as well [12].
236 The greatest challenge is the evaluation of PLCH disease
237 activity and, consequently, therapy effectiveness. In recent
238 years, based on a contrasting rate of glucose utilization
239 between rapidly proliferating tumor cells and surrounding
240 normal tissue, much attention has been devoted to the benefit
241 of FDG-PET and FDG-PET/CT scan imaging for determin-
242 ing the extent of Langerhans cell histiocytosis and therapy
243 response evaluation.
244 Derenzini et al. [13] used FDG-PET for evaluating the
245 effectiveness of MACOP-BQ2 chemotherapy in four patients.
246 The FDG-PET scan was able to detect additional lesions
247 missed by other modalities in two patients. A negative
248 interim FDG-PET predicted a long-lasting remission in three
249 of four patients. Phillips et al. [14] published the same
250 experience as they compared the benefit of FDG-PET/CT to
251 bone scans, CT, magnetic resonance imaging (MRI) and
252 conventional radiography for determining the extent of
253 Langerhans cell histiocytosis and evaluation of therapy
254 response in 44 patients (41 children and 3 adults). They
255concluded that whole-body FDG-PET scans can detect
256disease activity and early response to therapy with greater
257accuracy than other imaging modalities in patients with
258Langerhans cell histiocytosis affecting bones and soft
259tissues. Furthermore, FDG-PET is also beneficial for an
260early diagnosis of neurodegenerative Langerhans cell
261histiocytosis [15].
262However, a MEDLINE literature search revealed only
263one paper evaluating FDG-PET scan imaging in PLCH, the
264work from authors Krajicek et al. [16], who described their
265cohort study with 11 patients. PET-scan-positive patients
266had predominantly nodular lung disease with more than 100
267nodules usually under 8 mm in size, whereas PET-scan-
268negative patients had predominantly cystic lung disease with
269nodules numbering less than 25 in a field of examination.
270In our study, all pathology in the lung parenchyma was
271below detectable levels of the PET scanner (less than 7 mm),
272and we did not find large active lesions. Notwithstanding the
273observations of Krajicek et al., we describe a new
274methodology for diffuse metabolic activity evaluation of
275the lung parenchyma and present the possibility to objectify
276the results by comparing them with the simultaneously
277measured activity of the reference liver parenchyma. The
278evaluation of pulmonary activity based on the index, the ratio
279of the measured SUVmax value in a spherical volume of the
Table 3t3:1
An overview of PET-CT data in 7 patients with PLCHt3:2
t3:3 Date of
birth, Sex
Date of
PET-CTa
Applied
activity (MBq)
Blood glucose
levels (mmol/L)
SUVmax
PULMO
SUVmax
HEPAR
SUVmax
PULMO / SUVmax
HEPAR
t3:4 1972, M Mar-04 327 4.4 0.80 1.83 0.44
t3:5 Jan-05 321 5.8 0.81 1.79 0.45
t3:6 Feb-07 335 4.1 1.02 2.01 0.51
t3:7 Jun-08 337 4.8 1.06 2.24 0.47
t3:8 Jan-09 315 5.2 0.92 3.22 0.29
t3:9 Feb-10 352 4.7 0.89 3.25 0.27
t3:10 1974, M Mar-09 414 4.6 0.93 4.39 0.21
t3:11 Feb-10 431 4.8 0.89 3.25 0.27
t3:12 Jun-10 466 5.4 0.78 3.53 0.22
t3:13 1969, M May-09 377 4.7 1.88 3.30 0.57
t3:14 Mar-10 393 5.2 0.78 3.53 0.22
t3:15 1963, M Mar-09 372 4.7 1.78 3.11 0.57
t3:16 Aug-09 421 4.9 1.79 3.36 0.53
t3:17 Mar-10 401 4.7 1.03 2.71 0.38
t3:18 1973, M Jan-09 330 6.3 1.34 2.49 0.54
t3:19 Jun-09 336 5.6 0.68 2.23 0.31
t3:20 Nov-09 330 5.3 1.18 3.24 0.36
t3:21 Jan-10 338 5.7 0.88 3,30 0.27
t3:22 Jul-10 317 5.5 0.75 2.72 0.28
t3:23 Oct-10 292 6.4 1.40 2.98 0.48
t3:24 1963, M Jul-08 338 4.7 0.69 3.30 0.21
t3:25 Feb-10 354 5.1 0.95 3.96 0.24
t3:26 1955, F Mar-04 344 4.4 1.02 2.45 0.42
t3:27 Jan-09 337 5.8 1.00 3.19 0.31
t3:28 Mar-10 357 6.7 0.48 3.49 0.14
t3:29 May-10 351 5.4 0.53 3.15 0.17
t3:30 Oct-10 386 7.0 1.45 3.8 0.38
a
Between 2004-2007 only PET scans were made.t3:31
6 P. Szturz et al. / Nuclear Medicine and Biology xx (2011) xxx–xxx
280 right lung to the measured SUVmax value in a spherical
281 volume of the liver — the SUVmaxPULMO/SUVmaxHE-
282 PAR index — which we propose and which we have
283 verified, has not been published so far. We are aware of the
284 fact that the method we used is not common and, with such
285 small lesions, it is negatively biased by the partial-volume
286 effect characterized by increasing underestimation of SUV
287 with decreasing lesion sizes [17]. The index may be
288 influenced by concomitant factors affecting either lungs or
289 liver (e.g., other interstitial lung diseases, benign tumors,
290 active infections or noninfectious inflammations, cholesta-
291 sis, cirrhosis). Moreover, hyperinsulinemia [18], higher
292glucose level [19] and advanced age [20] were found to be
293related to increased FDG uptake by liver.
294Currently, except for HRCT of the lungs and pulmonary
295function tests, there is no other modality that informs more
296accurately on PLCH activity. Traditional FDG-PET scan
297imaging is not possible due to the small size of nodules
298which cannot be reliably resolved by the PET scanner.
299Therefore, we consider the measuring and long-term
300monitoring of the index SUVmaxPULMO/SUVmaxHEPAR
301to be very useful additional tools for PLCH activity
302evaluation. Based on our analysis of a sample of 100
303randomly chosen PET/CT scans, as mentioned above, and on
Fig. 4. Series of FDG-PET/CT images of a patient with multisystemic Langerhans cell histiocytosis with pulmonary involvement (male, born 1973). High index
value on admission PET/CT together with pathognomonic HRCT finding (multiple small nodules with sporadic cysts) and clinical symptoms (dyspnea, cough)
was diagnostic for PLCH. Interim PET/CT after two cycles with cladribine shows a therapy response which correlated with regression of lymphadenopathy
and relief of the symptoms, including perianal pruritus and B-symptoms (night sweats, fever and weight loss). However, an aggressive form of Langerhans
cell histiocytosis with recurrent relapses was the case. The index value corresponded closely with the disease course. We consider myocardial FDG uptake to
be physiological.
7P. Szturz et al. / Nuclear Medicine and Biology xx (2011) xxx–xxx
304 this retrospective study, we found that SUVmaxPULMO/
305 SUVmaxHEPAR index values higher than 0.5 bear high
306 probability of pulmonary involvement in patients with
307 Langerhans cell histiocytosis.
308 In conclusion, measuring the SUVmaxPULMO/SUV-
309 maxHEPAR index and its time-trend monitoring represent
310 simple noninvasive screening tools for PLCH, allowing us to
311 optimize the therapeutic management in the patients. An
312 early diagnosis of pulmonary involvement with a prompt
313 initiation of therapy may prevent progressive cystic damage
314 to the lungs. The index measurement also enables an
315 effective monitoring of therapy response and follow-up of
316 patients with PLCH.
317 Acknowledgment
318 This work was supported in part by the IGA
319 of The Ministry of Health (NT11154, NS10387,
320 FUNDIN MZ0MOU2005); The Ministry of Education,
321 Youth and Sports (LC06027, MSM0021622434); and
322 MUNI/A/1012/2009.
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