European Journal of Nuclear Medicine and Molecular Imaging

, Volume 32, Issue 9, pp 1011–1017

67Ga-SPECT/CT with a hybrid system in the clinical management of lymphoma

Authors

    • Nuclear Medicine Section, Department of Radiological SciencesUniversity of Perugia
  • Silvio Sivolella
    • Nuclear Medicine Section, Department of Radiological SciencesUniversity of Perugia
  • Isabella Palumbo
    • Internal Medicine and Oncology, Department of Clinical and Experimental MedicineUniversity of Perugia
  • Anna Marina Liberati
    • Internal Medicine and Oncology, Department of Clinical and Experimental MedicineUniversity of Perugia
  • Renato Palumbo
    • Nuclear Medicine Section, Department of Radiological SciencesUniversity of Perugia
Original Article

DOI: 10.1007/s00259-005-1788-x

Cite this article as:
Palumbo, B., Sivolella, S., Palumbo, I. et al. Eur J Nucl Med Mol Imaging (2005) 32: 1011. doi:10.1007/s00259-005-1788-x

Abstract

Purpose

The purpose of this study was to investigate the added value of co-registered fusion imaging using a hybrid system in patients with lymphoma.

Methods

Twenty-four lymphoma patients underwent 67Ga-SPECT/CT using a hybrid tomograph consisting of a dual-head, variable-angle gamma camera and a low-dose X-ray tube. Results were compared with those of SPECT alone.

Results

Forty-five lesions were identified by SPECT alone, while 49 were detected by SPECT/CT. Forty out of the 45 lesions observed on SPECT were confirmed as lymphoma, but five were due to other causes (thoracic aorta blood pool activity, sialoadenitis in the submandibular gland, bowel activity, rib fracture and bone marrow activation due to radiotherapy). SPECT/CT identified nine more neoplastic lesions compared with SPECT alone: four areas of radiopharmaceutical accumulation were observed in para-aortic lymph nodes, three in the spleen, one in the liver and one in para-iliac lymph nodes. In five cases, SPECT/CT provided additional anatomical information over SPECT alone. In four patients, four large areas of 67Ga uptake (one mediastinal, two supraclavicular and one para-aortic) were better characterised; in one subject uptake was localised in the seventh thoracic vertebra only by SPECT/CT. Hybrid imaging provided additional data in 13 patients (54.2%), thus inducing oncologists to reconsider the therapeutic approach in eight subjects (33.2%): unnecessary treatment was avoided in four (16.6%) while therapy was altered in another four (16.6%).

Conclusion

SPECT/CT hybrid system is able to provide information not obtained by SPECT alone. It allows the anatomical localisation of lymphoma and physiological radiopharmaceutical uptake, facilitates the diagnosis of tumours located in the abdomen (subdiaphragmatic lesions) and provides information that may cause a change in therapeutic strategy.

Keywords

LymphomaGallium-67 scintigraphyHybrid imaging systemSPECT/CT

Introduction

The clinical management of Hodgkin’s disease (HD) and non-Hodgkin lymphoma (NHL) entails initial staging and monitoring of therapeutic effectiveness at follow-up. Diagnostic imaging modalities employed in these contexts provide either morphological [computed tomography (CT), magnetic resonance imaging (MRI)] or functional [single-photon emission computed tomography (SPECT), positron emission tomography (PET)] information [13].

Among the single-photon-emitting radiopharmaceuticals, 67Ga-citrate (67Ga) is considered a cornerstone [3] in the evaluation of lymphoma. It is widely known that 67Ga uptake is an indicator of viable lymphoma, while no uptake is typical of fibrotic tissue. As a consequence of this ability to differentiate between residual viable tumour lesions and fibrotic tissue after treatment, 67Ga has been widely used in investigating response to therapy [3, 4]. 67Ga scan has shown predictive value in differentiating between patients with a favourable and those with an unfavourable prognosis, the outcome being more favourable in patients with a negative scan and varying according to the number of chemotherapy cycles required before a negative scan is obtained [5, 6].

Although the superiority of PET with 18F-fluorodeoxyglucose (18F-FDG) over 67Ga scintigraphy has been documented [7, 8], it has to be remembered that PET scan is not available in most nuclear medicine centres. On the other hand, recent findings [9, 10] have shown that fusion imaging with 67Ga-SPECT and CT is of significance in improving diagnosis by allowing precise localisation of radiopharmaceutical uptake and detection of lesions not demonstrated by CT. However, despite the availability of hybrid imaging systems with an X-ray tube mounted on a dual-head gamma camera gantry that are able to co-register SPECT and CT images in a single session, few findings have been reported in the literature on the use of 67Ga-SPECT/CT in lymphoma [9]. To our knowledge only some abstracts [1113] have presented data on examination of lymphoma patients with a hybrid tomograph.

With the aim of investigating the additional value of 67Ga-SPECT/CT performed with a hybrid system in comparison with SPECT alone in the clinical management of lymphoma, we studied patients with HD and NHL who had supra- and subdiaphragmatic lesions.

Materials and methods

Twenty-four patients with lymphoma (21 HD, 3 NHL; 9 males, 15 females; age range 15–54 years) were investigated by 67Ga-SPECT/CT. Diagnosis of lymphoma was performed by biopsy. Patients were treated by chemotherapy and radiotherapy. The characteristics of the subjects studied are shown in Table 1. All patients underwent CT scan and/or MRI. Patients imaged for initial staging (n=9) underwent CT before the beginning of treatment, while other subjects did so at mid-treatment or at the end of therapy. Patients were recruited to undergo SPECT/CT if they were scheduled to undergo initial staging or if they presented a residual mass on CT or MRI during or after therapy.
Table 1

Characteristics of the patients

Patient no.

Gender/age (yrs)

Histology

Clinical stage

Therapy

Aim of SPECT/CT imaging

1

M, 36

HD (NS)

IIA

ABVD, EBRT (30.6 Gy)

Treatment evaluation

2

M, 24

HD (NS)

IIA

Mega-CEOP, MAD, BEAM, ABMT

Treatment evaluation

3

F, 28

HD (NS)

IIB

ABVD

Treatment evaluation

4

F, 44

HD (NS)

IIB

 

Staging

5

M, 28

HD (NS)

IIIB

MOPP, HDS

Treatment evaluation

6

M, 33

HD (NS)

IIB

 

Staging

7

F, 54

HD (NS)

IIA

ABVD

Treatment evaluation

8

F, 30

HD (MC)

IIB

 

Staging

9

M, 23

HD (NS)

IIA

ABVD

Treatment evaluation

10

F, 30

NHL (large B cell)

IIA

Mega-CEOP, MAD, rituximab

Treatment evaluation

11

F, 36

HD (MC)

IIIB

 

Staging

12

F, 16

HD (NS)

IIB

ABVD, EBRT (30.6 Gy)

Treatment evaluation

13

M, 28

HD (NS)

IIB

BEACOPP, EBRT (30.6 Gy)

Treatment evaluation

14

F, 34

HD (NS)

IVB

 

Staging

15

F, 24

HD (NS)

IVB

 

Staging

16

F, 15

HD (MC)

IIA

ABVD, EBRT (30.6 Gy)

Treatment evaluation

17

F, 48

HD (MC)

IIB

ABVD, EBRT (30.6 Gy)

Treatment evaluation

18

F, 48

HD (MC)

IIB

ABVD, EBRT (30.6 Gy)

Treatment evaluation

19

F, 27

HD (NS)

IIB bulky

 

Staging

20

M, 27

HD (MC)

IIA

ABVD, EBRT (30.6 Gy)

Treatment evaluation

21

F, 24

HD (NS)

IIA

 

Staging

22

F, 49

NHL (large B cell)

IIA E bulky

Mega-CEOP, MAD BEAM, ABMT, EBRT (36 Gy)

Treatment evaluation

23

M, 34

HD (NS)

IIIB

 

Staging

24

M, 35

NHL (centrofollicular)

IVA

Mega-CEOP, rituximab, EBRT (30.6 Gy)

Treatment evaluation

HD Hodgkin’s disease, NHL non-Hodgkin’s lymphoma, NS nodular sclerosis, MC mixed cellularity, ABVD doxorubicin, bleomycin, vinblastine and dacarbazine, Mega-CEOP cyclophosphamide, epirubicin, vincristine and prednisone, MAD mitoxantrone, dexamethasone and cytarabine (Ara-C), BEAM carmustine, etoposide, cytarabine and melphalan, MOPP mechlorethamine, vincristine, procarbazine and prednisone, HDS high dose sequential, BEACOPP bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone, ABMT autologous bone marrow transplantation, EBRT external beam radiotherapy

SPECT/CT was performed by means of a hybrid system (Millennium VG-Hawkeye; General Electric Medical System, Milwaukee, WI) comprising a dual-head variable gamma camera equipped with a CT scanner. This device consists of two rectangular detectors with a field of view of 40×54 cm positioned at 180°, with 3/8 in. (9.5 mm) thick Na (I) crystals. The X-ray tube and linear detector array are located on the slip gantry of the gamma camera; to acquire data they continuously rotate together with the detector heads around the patient in a fixed geometry. The CT scanner is a low-end third-generation system with a low-power X-ray tube with 384 detectors (each 1.87×28 mm) fixed on the opposite side of the gamma camera gantry. The X-ray tube works in the continuous output mode during acquisition of each transaxial slice; the output is selectable to a maximum of 140 kVp at 2.5 mA. The X-ray tube is collimated to obtain a photon fan beam expanding to fill the linear array field of view in the transverse direction, with a beam width of 10 mm at the centre of the scan field in the axial direction. To acquire images, the patient is positioned for X-ray transmission scanning and 40 transverse slices are obtained as the patient is indexed through the imaging field of the imaging system by means of the computer-controlled imaging table. For CT scanning the system rotates at 2.6 rpm, a single slice being imaged in 13.8 s with 0.6 rotations. The acquisition time for 40 slices is about 10 min. Automatic repositioning of the patient is performed at the end of transmission scanning to allow for the 40-cm axial field of view to match the 40-cm axial field of view of the gamma camera. SPECT scan acquisition time is about 30 min.

SPECT images were acquired with a medium-energy high-resolution collimator 48 h after intravenous administration of 185–296 MBq. Four patients with subdiaphragmatic involvement at 48 h SPECT/CT imaging underwent SPECT again at 72 h to confirm the exclusion of bowel activity. Each patient underwent a single SPECT/CT session carried out in the region where CT scan evidenced suspected disease (thorax in 18 subjects, abdomen in six). The matrix size was 128×128 over 360°, with a 3° step, a duration of 45 s per frame and a zoom factor of 1.28. Images were reconstructed from raw data to transaxial slices by filtered back-projection with a Butterworth filter (cut-off 0.28; order 10). Coronal and sagittal slices were thereafter generated. For CT data, a “half-scan” acquisition over 220° in 14 s for each transaxial slice was carried out; multiple slices were acquired by moving the table by a slice step before the acquisition of the next slice. CT data were reconstructed by means of the nuclear medicine workstation (eNTEGRA, General Electric Medical System, Milwaukee, WI), using filtered back-projection (256×256 matrix) to provide cross-sectional attenuation images in which each pixel corresponds to the attenuation of the imaged tissue. The matching radiographic and nuclear medicine data were fused by eNTEGRA software, thus generating images showing the SPECT image overlying the CT scan.

67Ga-SPECT images were blindly evaluated by experienced nuclear medicine physicians (B.P., S.S., R.P.). Scintigraphic images were considered negative when no radiopharmaceutical uptake was demonstrated outside the areas of physiological uptake and positive when abnormal uptake was observed, i.e. outside the physiological activity distribution. SPECT/CT images were interpreted consensually by two nuclear medicine physicians (B.P., S.S) and a colleague who is a specialist in radiology and nuclear medicine (R.P.).

SPECT/CT findings were confirmed by CT scan data and/or MRI and clinical follow-up (for at least 6 months) and compared with SPECT images alone obtained from the same patients.

Results

Among the 24 patients examined, 45 lesions were identified by SPECT alone while 49 were detected by SPECT/CT. Forty out of the 45 lesions observed at scintigraphic imaging were confirmed to be neoplastic disease, while five had another origin. SPECT/CT allowed the identification of a further nine neoplastic lesions as compared with SPECT alone: four areas of radiopharmaceutical accumulation were observed in para-aortic lymph nodes, three in the spleen, one in the liver and one in para-iliac lymph nodes, as reported in Table 2. Figure 1 shows SPECT/CT of an HD patient (no. 11) undergoing staging evaluation. The five false positive lesions revealed by SPECT were correctly diagnosed by SPECT/CT, as disclosed in Table 3. False positive uptake was due to various causes: blood pool activity in the thoracic aorta, sialoadenitis in the submandibular gland, bowel activity, recent rib fracture and bone marrow activation (tracer uptake in the 12th thoracic vertebra) due to radiotherapy. False positive uptake of benign origin was confirmed by other diagnostic procedures, i.e. ultrasonography for sialoadenitis and radiographic examination for rib fracture. Figure 2 shows the SPECT/CT results of an NHL patient (no. 24) at treatment evaluation (at 1 year of follow-up). 67Ga uptake in the 12th thoracic vertebra is observed and could be attributed to the effects of radiation therapy. To confirm this condition, the patient also underwent MRI, bone scintigraphy and colloid scan. MRI disclosed bone marrow activation in the 12th thoracic vertebra, bone scintigraphy showed no radiopharmaceutical uptake and colloid scan revealed mild tracer uptake in the vertebra in question. Therefore the hypothesis of bone marrow activation due to radiotherapy was considered valid, although the patient had finished radiotherapy 4 months before SPECT/CT imaging.
Table 2

Additional value of SPECT/CT imaging compared with SPECT in cases that yielded false negative results at SPECT

Patient (no.)

No. of lesions

SPECT findings

SPECT/CT findings

11

2

Inhomogeneous splenic uptake

Focal uptake in the spleen (posterior horn)

Bowel activity

Para-aortic lymph node lesion

14

4

Inhomogeneous splenic uptake

Focal uptake in the spleen (posterior horn)

Inhomogeneous liver uptake

Focal lesion in the IVth hepatic segment

Bowel activity

Para-aortic lymph node lesion

Bowel activity

Para-iliac lymph node lesion

15

2

Inhomogeneous splenic uptake

Focal uptake in the spleen (anterior horn)

Bowel activity

Para-aortic lymph node lesion

20

1

Bowel activity

Para-aortic lymph node lesion

Fig. 1

67Ga SPECT/CT in a patient (no. 11) with HD (staging). Abnormal 67Ga uptake is shown in supraclavicular, axillary, paratracheal, parahilar and para-aortic lymph nodes and in the spleen, at lesion sites corresponding to those observed on CT. The para-aortic lymph node uptake combined with CT scan results allowed the diagnosis of subdiaphragmatic involvement, bowel activity having been excluded

Table 3

Additional value of SPECT/CT compared with SPECT in cases that showed false positive 67Ga uptake on SPECT

Patient (no.)

No. of lesions

SPECT findings

SPECT/CT findings

2

1

Left laterocervical lymph node uptake

Sialoadenitis

17

2

Paratracheal lymph node uptake

Rib fracture

Hepatic hilum lymph node uptake

Bowel activity

23

1

Mediastinal (paravertebral) lesion

Blood pool activity

24

1

Mediastinal (inferoposterior) lesion

Bone marrow activation

Fig. 2

67Ga SPECT/CT in a patient (no. 24) with NHL (treatment evaluation). Abnormal 67Ga uptake is shown in the 12th thoracic vertebra, at the lesion site evidenced by CT; this indicated bone marrow activation after radiotherapy

In five cases, SPECT/CT provided additional information concerning the anatomical characterisation of some lesions already identified by SPECT. In four patients, four large areas of 67Ga uptake (one mediastinal, two supraclavicular, one para-aortic) were better characterised by SPECT/CT, particularly with respect to proximity to and involvement of adjacent structures. In one subject, tracer uptake in the seventh thoracic vertebra was precisely localised as a bone lesion, while scintigraphic imaging alone was not able to correctly identify the lesion site.

Furthermore, SPECT/CT provided additional clinical data in 54.2% of the patients examined (13/24). In particular, SPECT/CT findings caused oncology physicians to reconsider the therapeutic approach in 33.2% of the subjects (8/24), based on altered staging as compared with previous CT or MRI results: upstaging occurred in 16.6% (4/24, three during treatment, one at staging) while downstaging occurred in another 16.6% (4/24, three at staging and one during treatment). Considering only the 15 treated patients, treatment strategy was modified in 26.6% (4/15) . Furthermore, among the nine patients undergoing staging evaluation, SPECT/CT results led physicians to classify four, i.e. 44.4%, at a different stage.

Discussion

This is the first clinical paper on the use of 67Ga-SPECT/CT with a hybrid system to study lymphoma patients. Nine more lesions below the diaphragm were detected by SPECT/CT as compared with SPECT alone. This is of particular interest because one limitation of 67Ga scintigraphy is its restricted ability to identify subdiaphragmatic disease: bowel activity due to radiopharmaceutical excretion can cause errors in interpretation, and delayed images are often required [3]. In our study, hybrid imaging allowed the exclusion of false negative conditions such as bowel activity. Bone marrow activation was observed in one of our patients, although he had finished radiotherapy 4 months before undergoing fusion imaging. According to the EANM guidelines, 67Ga scan should be performed at least 3–4 weeks after the last course of radiation therapy [14]. In the aforementioned patient, SPECT/CT was able to discern the precise localisation of tracer uptake (12th thoracic vertebra), allowing us to interpret this finding as an effect of radiotherapy on bone marrow. This interpretation was supported by other diagnostic tools (MRI, bone scan, colloid scintigraphy) excluding bone lesions such as tumour or arthropathy and documenting only bone marrow hyperactivity. Furthermore it has to be remembered that lesion sites already identified by scintigraphy alone were better defined by co-registered hybrid imaging and that the false positive lesions revealed by SPECT were correctly diagnosed by SPECT/CT, as disclosed in Table 3. It must be mentioned that although SPECT/CT is not able to define the benign or malignant nature of a lesion, it allows precise identification of the anatomical site of dubious radiopharmaceutical uptake that can subsequently be investigated by other diagnostic examinations (as occurred in the patient with sialoadenitis that was diagnosed by ultrasonography and the patient with rib fracture evaluated by radiography). These data are of clinical interest because 67Ga performance is improved by use of SPECT/CT fusion imaging, suggesting that this modality could represent an alternative to PET—considered the imaging option of choice in lymphoma assessment—if PET is not available.

Another important point to note is the opportunity of changing the treatment programme on the basis of SPECT/CT results. In our study, the therapeutic strategy was altered in 33.2% of the patients examined. Potentially toxic further treatment was avoided in 16.6% who were downstaged, while more aggressive therapy was adopted in 16.6% who were upstaged. Among the 15 treated patients, treatment was modified in 26.6% owing to altered staging. Although the number of the patients examined was not very large, these data are of significant clinical interest and should be supported by further studies.

Chajari et al. [9] investigated 38 patients with lymphoma (HD and NHL) by superimposition of 67Ga-SPECT and CT, obtaining a total of 52 fused examinations. They found an improvement in diagnosis in 12 studies (23%), which led to alteration of treatment in only four patients. They concluded that, although the most appropriate indication for fusion imaging (initial staging, treatment evaluation or suspected recurrence) is not clear, SPECT/CT should be systematically performed to evaluate therapy in lymphoma patients with bulky lesions because the accuracy of both examinations can be improved. In our group of patients, therapeutic decisions were amended in a higher percentage of patients than in the aforementioned study. We share their opinion, however, that further studies are necessary to strengthen the results.

A further relevant consideration has to be examined. The study of Chajari et al.[9] was carried out by superimposition of SPECT and CT registered at different times. This procedure requires that both examinations are performed on the same day, that the subject is imaged in the same position and that external markers are carefully matched [9, 10]. Integrated SPECT/CT devices have the advantage of faster co-registered acquisition and absence of differences due to patient positioning; the only problem is breathing motion, which is also present when hybrid imaging is performed [9]. However, breathing motion is of minor importance in imaging of the abdomen and pelvis, which represent the elective indications. The increasing significance of SPECT/CT hybrid systems in the clinical evaluation of different diseases has been documented in recent years by international literature. Schillaci and co-workers first employed this hybrid device to better define the anatomical site of various kinds of disease and particularly tumours [15, 16]. As regards neoplastic disorders, the authors underlined the role of hybrid systems in investigating neuroendocrine tumours, showing that SPECT/CT fused images were capable of providing additional data that improved the accuracy of SPECT interpretation and led to changes in therapy [16]. Another interesting paper from this group [17] reported on the clinical role of hybrid SPECT/CT in investigating hepatic haemangiomas. SPECT/CT with 99mTc-labelled red blood cells was shown to be useful in correctly characterising liver lesions located near the heart or major intrahepatic vessels, allowing accurate anatomical assessment of increased blood pool activity sites in 33.3% of the patients. Tharp and collaborators [18] studied the diagnostic impact of 131I-SPECT/CT compared with conventional scintigraphic evaluation in the follow-up of patients with thyroid carcinoma. They observed that integrated SPECT/CT was able to correctly characterise equivocal tracer uptake on planar imaging and could also localise neck, chest and bone neoplastic lesions. Furthermore they observed that the hybrid system was valuable in optimising localisation of 131I uptake to lymph node metastases versus remnant thyroid tissue, to lung versus mediastinum and to the skeleton.

Conclusion

In conclusion, SPECT/CT with 67Ga plays a relevant role in the diagnostic imaging of supra- and subdiaphragmatic lymphoma because it is able to provide additional information of clinical value. It may be considered a valid alternative to PET if this diagnostic modality is not available.

Copyright information

© Springer-Verlag 2005