Lymph glands, lymphatics and tumours

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Chapter 11 Lymph glands, lymphatics and tumours

Positron Emission Tomography Imaging

Positron emission tomography (PET) imaging is a technique used to detect and accurately stage malignant disease, to differentiate benign and malignant tissue, and to assess response to treatment. Until recently, PET imaging availability was restricted due to high capital cost and logistics of radiopharmaceutical supply. It uses short-lived cyclotron-produced radionuclides such as 18Fluorine, 11Carbon, 13Nitrogen and 15Oxygen with half-lives of 110, 20, 10 and 2 min respectively. 18Fluorine is the only one of these that has a half-life long enough to allow it to be produced off-site. This does permit 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG), the single most important PET radiopharmaceutical, to be used by sites without their own cyclotron.

The widespread acceptance of PET as a major advance is due to two major factors:

1. There is increased recognition in the literature of the role of the main PET tracer 18F-FDG, a glucose analogue that is taken up in tissue in proportion to cellular glucose metabolism. This is particularly useful for tumour imaging, since most tumours have increased glucose metabolism and will concentrate FDG. Malignant cells are characterized by increased glucose transporter molecules at the cell surface. FDG is phosphorylated by the enzyme hexokinase to a polar intermediate which does not cross cell membranes well and is, therefore, trapped in the cell. Hexokinase levels and activity are increased in malignant cells. The reverse reaction (glucose-6-phosphatase) is slow and the enzyme is commonly deficient in cancer cells.
2. Integrated PET CT scanners are now available. These units have separate PET and CT scanners installed in the same gantry. The patient undergoes a conventional CT scan (usually performed with low exposure factors to reduce radiation dose) immediately followed by a PET scan without moving on the same table-top. This allows fusion of the anatomical information from CT with the functional data from the PET scan, and hence accurate anatomical localization of metabolically active disease. The density data from the CT scan is also used to correct the PET data for differential attenuation of the emitted photons within the patient.

Normal physiological uptake is seen in organs that are hypermetabolic and big glucose users especially the brain and the heart, or active or recently active skeletal muscle. Variable uptake is seen in the gut and there is normal excreted urinary activity in the urinary tract. One confounding factor for interpretation may be normal physiological uptake in brown fat – particularly in the neck and paraspinal regions. Differentiation of this normal activity from pathology is greatly aided by the co-registration afforded by combined PET CT scanners.

However, FDG is not specific for cancer cells as any hypermetabolic cell such as those in sites of inflammation or infection will show increased uptake of FDG, so interpretation with reference to full clinical details and other imaging is important to avoid false-positive scans.

As the only PET tracer likely to be widely available in the near future, this section is restricted to FDG imaging. Discussion is also limited to the role of PET in oncological patients.

2-[18F]FLUORO-2-DEOXY-D-GLUCOSE (18F-FDG) PET SCANNING

Indications (oncology)

General

1. Distinguishing benign from malignant disease, e.g. lung nodules, brain lesions, etc.
2. Establishing the grade of malignancy, e.g. brain tumours, soft-tissue masses
3. Establishing the stage of disease, e.g. lung cancer, lymphoma, etc.
4. Establishing whether there is recurrent or residual disease, e.g. lymphoma, teratoma, seminoma, etc.
5. Establishing the site of disease in the face of rising tumour markers, e.g. colorectal, germ cell tumours, etc.
6. Establishing the response to therapy – pre, during and post therapy imaging
7. Identifying occult malignancy, e.g. paraneoplastic syndrome or the unknown primary in the setting of proven metastatic disease.

Specific

The following tumour specific indications are supported by grade A or grade B evidence (A: randomized controlled clinical trials, meta-analyses and systematic reviews; B: robust experimental or observational studies; C: other evidence where the advice relies on expert opinion and has the endorsement of respected authorities):

1. Lung cancer:

a Characterization of solitary pulmonary nodule where biopsy is not possible
b Staging of non-small cell lung cancer prior to surgery or radical radiotherapy.

2. Lymphoma:

a Assessment of residual masses post chemotherapy for disease activity

3. Colorectal cancer:

a Differentiation of local recurrence from post surgical or post radiotherapy fibrosis
b Exclusion of distant metastases prior to resection

4. Oesophageal cancer:

a Primary staging

5. Melanoma:

a Detection of distant metastases (sentinel node mapping preferred for regional nodal disease)

6. Thyroid cancer:

a Raised thyroglobulin; negative I-131 scan

7. Seminoma/teratoma:

a Assessing recurrent disease from seminoma or teratoma
b Residual masses post treatment

8. Soft-tissue sarcoma:

a Staging and grading

9. Other indications; there are other scenarios where PET may well be useful, but either the numbers are smaller or the evidence is more limited or less robust.

Contraindications

1. Recent chemotherapy – minimum interval of 2–3 weeks recommended
2. Recent radiotherapy – minimum interval of 8–12 weeks recommended
3. Poorly controlled diabetes, i.e. serum glucose >8.5 mmol l−1 at time of scanning.

Patient preparation

1. Fasting for 4–6 h, with plenty of non-sugary fluids
2. Monitor blood glucose before injection to ensure it is not elevated. Elevated blood glucose levels result in diversion of glucose to muscle. Consider rescheduling patient if blood glucose elevated. Administration of insulin is counter-productive as this diverts glucose uptake to muscle
3. A mild sedative such as diazepam may be given to reduce physiological muscle and brown fat uptake
4. Oral contrast may be administered to aid interpretation of the CT. Attenuation correction artifact on the PET images secondary to the high-density contrast has been shown not to be clinically significant.

Technique

1. Up to the UK limit of 400 MBq 18FDG intravenously (i.v.) (10 mSv effective dose (ED)) is administered.
2. To reduce muscle uptake of FDG, patients should remain in a relaxed environment such as lying in a darkened room (without talking if head and neck area are being imaged) between injection and scan.
3. Image at 1 h post injection. Later imaging has been reported to enhance tumour conspicuity due to a higher tumour to background ratio.
4. Imaging is preferred with the arms above the head to reduce beam hardening artifact on the CT.
5. CT:

a Low dose
b No i.v. contrast medium
c Positive or negative oral contrast agents according to local protocol are increasingly being used.

6. PET:

a From the base of skull to upper thighs (occasionally extended if melanoma or limb or head and neck tumours)
b 3–4 min for each of 5–6 bed positions for the PET

7. In some instances a diagnostic standard dose CT with i.v. contrast may be acquired as well, but in routine practice a diagnostic scan will usually be already available.

Other applications

Coronary artery disease (Chapter 8)

Assessment of myocardial viability.

Neurology (Chapter 13)

1. Location of epileptic foci
2. Assessment of dementia.

Further reading

British Nuclear Medicine Society Web Site guidelines –. www.bnms.org.uk, 2008.

.

Cook G.J., Wegner E.A., Fogelman I. Pitfalls and artifacts in 18FDG PET and PET/CT oncologic imaging. Semin. Nucl. Med.. 2004;34(2):122-133.

Kapoor V., McCook B.M., Torok F.S. An introduction to PET CT imaging. RadioGraphics. 2004;24(2):523-543.

Rohren E.M., Turkington T.G., Coleman R.E. Clinical applications of PET in oncology. Radiology. 2004;231(2):305-332.

von Schulthess G.K., Steinert H.C., Hany T.F. Integrated PET/CT: current applications and future directions. Radiology. 2006;238(2):405-422.

Gallium Radionuclide Tumour Imaging

This is rarely used, having almost entirely been superseded by cross-sectional techniques and PET scanning.1 The main disadvantages are the high radiation dose, the extended nature of the investigation, its non-specific nature, and difficulties in interpretation in the abdomen due to normal bowel activity.

Indications

1. Hodgkin’s and non-Hodgkin’s lymphoma: assessment of residual masses after therapy and early diagnosis of recurrence1
2. Gallium imaging has been used with variable success in a variety of other tumours, e.g. hepatoma, bronchial carcinoma, multiple myeloma and sarcoma
3. It has also been used in benign conditions such as sarcoidosis and for localization of infection or in suspected orthopaedic infection

Contraindications

None.

Radiopharmaceutical

67Ga-Gallium citrate, 150 MBq maximum (17 mSv ED).

Normal accumulation is seen in the liver, bone marrow and nasal sinuses, and variably in the spleen, salivary and lacrimal glands. There is significant excretion via the gut and some via the kidneys. 67Ga has a half-life of 78 h and principal γ-emissions at 93, 185 and 300 keV, so image quality is fairly poor.

Equipment

1. Gamma camera, preferably with whole-body and single-photon emission computed tomography (SPECT) facilities
2. Medium- or high-energy collimator.

Patient preparation

If the abdomen is being investigated, laxatives may be given (if not contraindicated) for 2 days after injection of 67Ga-citrate to clear bowel activity. Additionally, an enema or suppository may be given on the day of imaging.

Technique

1. 67Ga-citrate is administered i.v.
2. Delayed images are acquired as below with energy windows about the lower two or all three of the main photopeaks.

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