Radiopharmaceuticals

The advantageous properties of 99mTc were reported by Richards (1960) and Harper et al. (1965), but it was not until the introduction of triphosphate complex by Subramanian and McAfee (1971) that 99mTc became the most promising bone scan agent. Thus, this initial work on 99mTc-labeled phosphate compounds opened a path to the development of a series of novel bone scan agents. Within a short period of time, 99mTc-labeled polyphosphate, pyrophosphate, and diphosphonate were developed in series for general use. Chemically, phosphate compounds contain a plural number of phosphate residues (P-O-P), the simplest form being pyrophosphate with two residues. Phos-phonate has P-C-P bonds instead of P-O-P bonds and diphosphonates are most widely used. Now these are available as 99mTc-labeled hydroxydiphosphonate (HDP) and 99mTc-la-beled MDP. The phosphonate compounds have a strong avidity for hydroxyapatite crystal, especially at the sites where new bone is actively formed as in the physeal plates of growing long bones.

Following intravenous injection, 99mTc-phosphate and 99mTc-diphosphonate are rapidly distributed in the extracellular fluid space of the body, and about half of the injected tracer is fixed by bone and the remainder excreted in the urine by glomerular filtration (Alazraki 1988). According to Davis and Jones (1976), the amount of radiotracer accumulated in bone

Pinhole Collimator Bone Scan
Fig. 1.4 Schematic diagram showing inversion and magnification of pinhole image. D Diameter of detector or crystal, t thickness of detector, a collimator length or detector-to-aperture distance, d aperture-to-object distance, a acceptance angle

(REC), and granulopoietic cells. Phagocytosis is the mechanism by which 99mTc-colloids visualize REC. Unfortunately, red marrow uptake of currently available 99mTc-colloids is not large enough to produce marrow image of sufficient quality. In addition, disparity may occur between the locations of REC and hematopoietic cells in different hematological disorders. Theoretically, 52Fe and 59Fe can be used for the imaging of erythropoietic bone marrow, but their unsuitable physical characteristics prevent practical use. 111In-chloride has been tested as an iron substitute, but has been found not to be satisfactory (Lilien et al. 1973). 111In-chloride is an expensive agent.

1.6 Fundamentals of Pinhole Scintigraphy

1 h after injection is 58% with MDP, 48% with HEDP, and 47% with pyrophosphate. The latest form of the diphosphonate series is disodium-monohydroxy-methylene diphosphonate (oxidronate sodium, CH4Na2O7P2) marketed as TechneScan HDP. Its blood and nonosseous clearance is much faster than that of 99mTc-la-beled MDP, and the blood level is about 10% of the injected dose at 30 min with a rapid fall thereafter, reaching 5%, 3%, 1.5%, and 1% at 1 h, 2 h, 3 h, and 4 h, respectively, after injection (Mallinckrodt 1996). An advantage of this preparation is that an optimum blood level is reached as early as at 1-2 h after injection; as a result the scan time is conveniently reduced without increasing the tracer dose.

1.5 Bone Marrow Scan Radiopharmaceuticals

99mTc-nanocolloid and 99mTc-anti-NCA95 antibody are two representative agents for bone marrow scanning. These agents image erythro-poietic precursor cells, reticuloendothelial cells

This section considers the spatial resolution and sensitivity of the pinhole collimator as related to aperture size and aperture-to-target distance. In addition, the parameters that affect image quality are briefly discussed. For those interested in a mathematical presentation of this subject, a separate chapter is appended.

A scintigraphic image is the cumulative result of a number of physical parameters including (a) radionuclide, (b) amount of radioactivity, (c) collimator design, (d) detector efficiency, and (e) image display and recording devices. Other factors such as patient movement during scanning and various artifacts can also affect the spatial resolution, object contrast, and sensitivity, which all seriously affect lesion detectability (Appendix and Chap. 5).

The tracer must be localized to bone and deliver a low radiation dose while permitting a high count density in the target. In this respect, 99mTc with a half-life of 6.02 h and a monoenergetic gamma ray of 140 keV labeled to phosphates is ideally suited for bone scanning. As a rule, 740-925 MBq (20-25 mCi), or a slightly higher dose in the elderly who have

Picture Soft Tissure Colon
Fig. 1.5A, B Local recurrence of colon carcinoma. A Lateral planar bone scintigraph shows no abnormal tracer uptake (?). B Lateral pinhole scintigraph demonstrates minimal uptake in the presacral soft tissue, denoting recurrence (arrow)

reduced bone metabolic function, of 99mTc-MDP or 99mTc-HDP is injected with satisfactory results and an acceptably low radiation dose. Basically, a gamma camera system consists of a scintillation detector with collimator, electronic devices, and image display and recording devices. Of these, the collimator is probably the most important variable that affects image resolution. The primary objective of a collimator is to direct the gamma rays emitted from a selected source to scintillation detector in a specifically desired manner. Four different types of collimators are used: pinhole collimator, and parallel-hole, converging and diverging multi-hole collimators.

The pinhole collimator is a cone-shaped heavy-metal shield that tapers into a small aperture perforated at the tip at a distance a from the detector face, which may be either circular or rectangular in shape (Fig. 1.4). The geometry of the pinhole is such that it optically creates an inverted image of the object on the crystal detector from the photons traveling through the small aperture. The design is based on aperture diameter, acceptance angle a, collimator length a, and collimator material.

The aperture diameter of a pinhole collima-tor is the most important and direct determinant of the system's resolution and sensitivity. Evidently, the collimator with a smaller aperture diameter can produce a scan image with a higher resolution, but at the expense of sensitivity, and vice versa. Therefore, optimization of the two contradicting parameters is necessary. In practice, a collimator with an aperture diameter of 3 or 4 mm is optimal. The magnification, resolution, and sensitivity of a pinhole collimator acutely change with the aperture-to-target distance. Thus, image magnification with a true gain in both resolution and sensitivity can be achieved by placing the collima-tor tip close to the target.

Fundamentally, the suitability of pinhole scintigraphy largely depends on the size or area of the target to be imaged. Relatively small structures or organs such as the appendiceal bones and joints and thyroid gland are perfectly suited. In the same context a small portion of large anatomical structures such as the skull, spine, chest, long bone, and pelvis can also be imaged satisfactorily with rich diagnostic information.

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