Sources Used in Nuclear Medicine

In nuclear medicine, a radiopharmaceutical, also called an imaging agent or a tracer and containing a particular radionuclide in a specific chemical form, is administered orally or intravenously to a patient. Diagnostic imaging is the usual purpose but, less frequently, radiation therapy is performed.23 The radiation that is measured to obtain an image of an organ originates within the body rather than in an external source of x or y rays. Radionuclides suitable for diagnostic imaging decay by the emission of y rays that are detected by an array of detectors in a "y-ray camera,'' which, in the simplest planar procedure, provides an image showing abnormalities in the region in which uptake of the radionuclide has occurred.24 Radionuclides that decay by isomeric transition and electron capture have the advantage of not exposing the patient to high-energy particulate radiation. Suitable radionuclides must also have a relatively short half-life (minutes to days) and be readily incorporated into a nontoxic radiopharmaceutical.

A radiopharmaceutical contains a radionuclide in a chemical form that has been shown to concentrate in a specific organ (target organ) or region of the body. In a few radiopharmaceuticals, the radionuclide is present in a relatively simple chemical form. With few exceptions, the target organ of a radiophar-maceutical is not determined directly by the chemistry of the radionuclide, but by the chemistry of the organic or inorganic compound (e.g., an amino acid, a chelate, etc.) containing the radionuclide. Commonly used and y-emitting radionuclides are 51Cr (27.702 d), 67Ga (3.261 d), 99mTc (6.01 h), 111In (2.8049 d) 123I (13.2 h), 125I (59.4 d), 131I (8.0207d), 133Xe (5.243 d), and 201Tl (3.039 d). A few examples of specific radiopharmaceuticals and their

23An organic compound such as CH4 in which a significant fraction of the stable 12C atoms have been replaced by stable 13C or by radioactive 14C or 11C is an isotopically labeled compound. A compound such as Na99mTcO4, sodium pertechnetate, is not labeled in the same sense because there is no stable isotope of technetium. In a more general usage, the word "labeled" indicates that the compound contains a stable nuclide or a radionuclide that makes the compound suitable for a particular use.

24The camera is a y-ray detector with a specially configured shield of absorbing material to collimate the photons entering the detector.

diagnostic applications are listed in Table 14-6. The structure of one of these, technetium-99m sestamibi, is shown in Figure 14-9. The levels of activity needed for diagnostic imaging vary from about 200 kBq to 750 MBq (5.4 ^Ci to 20mCi).

TABLE 14-6

Examples of Diagnostic Radiopharmaceuticals

Radiopharmaceutical"2

Application

Gamma-ray emitters

51 Cr-EDTA

67Ga-citrate

99mTc-arcitumomab

99mTc-DMSA

99mTc-DTPA

99mTc-MAA

99mTc-MAG3

99mTc-nofetumomab merpentan 99mTc-pyrophosphate 99mTc-labeled red blood cells 99mTc-sestamibi 99mTc-sulfur colloid 111In-capromab pendetide 111In-imicromab pentetate 111In-labeled leukocytes 111In-DTPA 123I- (Na+ salt) 125 I-labeled antigen 1311- (Na+ salt) 201TlCl 133Xe

Positron emitters (annihilation photon emitters)

11 C-labeled compounds

11C-palmitate 13N-labeled compounds

13NH3 150-labeled compounds

H2[150] 18F-labeled compounds

18F-deoxyglucose 82Rb (As Rb+)

Renal tracer Tumor imaging

Thyroid function, blood flow, brain imaging

Imaging recurrent and/or metastatic colorectal carcinomas

Renal function

Renal function

Venous blood flow

Renal function

Detection of small-cell lung carcinoma Bone imaging Spleen imaging

Mycocardial perfusion imaging, imaging of breast lesions Liver imaging

Detection of recurrent and metastatic prostate cancer

Imaging damaged myocardial tissue

Imaging infections

Flow of cerebrospinal fluid

Thyroid function

Radioimmunoassay

Thyroid function

Myocardial perfusion

Lung ventilation

Metabolic studies

Long-chain fatty acid metabolism

Metabolic studies

Myocardial perfusion

Metabolic studies

Myocardial perfusion

Variety of studies

Glucose metabolism

Myocardial perfusion aEDTA, ethylenediaminetetraacetic acid; 99mTc-arcitumomab, radiolabeled monoclonal antibody; DMSA, dimercaptosuccinic acid; DTPA, diethylenetriaminepentaacetic acid; MAA, macroaggregated albumin; MAG3, mercaptoacetylglycylglycine; nofetumomab merpentan, radiolabeled monoclonal antibody; sestamibi, 2-methoxyisobutyl isonitrile (Figure 14-9); 99mTc sulfur colloid, Tc2S7; capromab pendetide and imicromab pentetate, radiolabeled indium monoclonal antibodies.

CIC NCN

III R

CH3 I 3

FIGURE 14-9 Sestamibi with "m Tc.

Two special diagnostic procedures are known as PET and SPECT. In positron emission tomography (PET), the radiopharmaceutical contains a positron emitter. The method is based on the fact that when a positron is annihilated, two photons (0.511 MeVeach) are emitted at 180° to each other (see Section 13.7.1.3). The point of annihilation in three-dimensional space can be determined accurately by counting the photons that arrive in coincidence in a pair of detectors that are positioned at 180° relative to each other. The pair of detectors can be rotated around the patient in a circular or oval path, as for CAT and MRI scanning, or the patient may be surrounded by an array of pairs of detectors. Computer-assisted reconstruction generates the images. PET is also useful for studying metabolic kinetics and blood flow in the brain. Examples of positron emitters incorporated in radiopharmaceuticals are 11C (20.3 m), 13N (9.97m), 150 (122.2 s), 18F (1.8295 h), 62Cu (9.74 m), and 82Rb (1.26 m). These radionuclides are produced with a dedicated particle accelerator, that is, apparatus located at or near the medical facility at which the positron emitters are used. Examples of production reactions are 12C(d, n) N, 14N(d,n)150, and 180(p, n)18F. Table 14-6 gives only a few of the many compounds that are labeled with positron emitters.

One positron-emitting imaging agent, 2-[18F]fluorodeoxyglucose (18FDG or FDG), which has been used over the years for evaluation of glucose metabolism and myocardial viability, also has chemical properties that make it suitable for identifying cancerous tissue and detecting false indications of cancer obtained in standard tests. It, unlike a radiopharmaceutical designed to bind to cells of a particular organ, is nonspecific. That is, it will find any cancerous tissue and detect metastases. The rapidly growing cells in such tissue have a higher need for glucose than normal cells and accept FDG as glucose only to find that it is an unusable permanent resident. FDG is more effective for fast rather than slowly growing cancer cells.

In single-photon emission tomography (SPECT), the camera or array of cameras rotates around the patient's body and provides data for reconstructing images of planes. This procedure provides images with greater contrast than those obtained with the planar procedure for the same radionuclide.

Certain short-lived radionuclides used to prepare radiopharmaceuticals can be obtained from "generators" that are commercially available. These generators contain a relatively large amount of the longer-lived parent of the radionuclide of interest. The shorter-lived daughter grows [equation (13-23)] and is removed chemically as needed. An example is the separation by simple chromatographic elution of 99mTc as the pertechnetate ion, 99mTcO—, from the 99Mo (2.7476 d) parent.25 Other generator-produced radionuclides include 62Cu from 62Zn (9.22 h) and 82Rb from 82Sr (25.36 d).

Technetium-99m has been called the workhorse of nuclear medicine for several reasons: (1) there seem to be an endless number of 99mTc compounds that can be used to target virtually any organ of the body, (2) its half-life is quite suitable, (3) its 7-ray energy (142.7 keV) is ideal for measurement, and (4) it is readily available from a generator. The versatility of Tc arises from its electron configuration (4d55s2 for the outer electrons in the ground state) and, therefore, oxidation states from —1 to + 7. Although 99mTcO—, the chemically stable form in which 99mTc is stored in aqueous solution, mimics I" and is itself used as a radiopharmaceutical, Tc(VII) is usually reduced to Tc(VI), Tc(IV), or Tc(III) before being combined with a ligand to form a radiopharmaceutical. In terms of the environment, it is of interest to note that 99mTc decays into 99Tc, a fission product and a pure 0 emitter with a half-life of 2.13 x 105 y.

Iodine-131 (8.0207d), which concentrates in the thyroid, is used not only diagnostically but also therapeutically to treat patients with hyperthyroidism and other thyroid diseases, including cancer, and after thyroidectomy. The quantities of 131I (as iodide) used for hyperthyroidism are about 222-333 MBq (6-9 mCi). Another radionuclide used for therapy is 32P (14.28 d) (as orthophosphate). It is used in the treatment of polycythemia vera, a condition in which the patient's blood has an abnormally high concentration of red cells. The quantity administered [up to about 185 MBq (5 mCi)] is limited by the extent of allowable irradiation of the bone marrow.

Additional examples of radionuclides that are used for radiotherapy (including radioimmunotherapy with labeled antigens to treat lymphoma and

25Molybdenum-99 can be made by neutron irradiation of molybdenum [i.e., 98Mo(n, 7)99Mo], or it can be separated from the other fission products produced by neutron irradiation of a sample of 235U.

leukemia) are 89Sr (50.52 d), 90Y (2.67 d), 125I (59.4 d), 153Sm (1.928 d), 186Re (3.718 d), 188Re (16.94 h), 198Au (2.6952 d), and 211At (7.21 h). Yttrium-90 can be obtained as needed from a generator containing its parent, 90Sr (28.78 y). The latter can be removed from fission product waste accumulated from reprocessed, neutron-irradiated 235U or 239Pu.

A radionuclide that is believed to show promise for destroying cancer by a-particle immunotherapy is bismuth-213 (45.6m, 97.8%, a 2.2%). The 213Bi is attached to an antibody that in effect transports the radionuclide to the cancer cells. This therapy has been effective in destroying the cancer cells that remain after chemotherapy treatment of acute myeloid leukemia.

The availability of 213Bi is rather interesting. It is a member of the 233U (1.592 x 105 y) decay series, which terminates in stable 209Bi rather than a lead isotope. It is the granddaughter of actinium-225 (10.0 d, a), which can be separated from 233U and can then be used as a 213Bi generator. Uranium-233, which has potential use in nuclear weapons or in fuel for nuclear reactors, has been made in kilogram amounts by neutron irradiation of 232Th and is in storage awaiting disposal.

It should be apparent that investigators with a good knowledge of the fundamentals and an interest in discovering new uses of radioisotopes for medical diagnosis and therapy, are limited only by ingenuity.

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