Biomolecular Magnification Imaging of Musculoskeletal Diseases

Abstract

The human musculoskeletal system has four functions: (1) body structuring with weight bearing and protection against extraneous forces, (2) locomotion, (3) calcium storage and liberation, and (4) hematopoiesis. Of these, the structure or anatomy and the molecular profile or metabolism of bone calcium can be imaged using ^99mTc methyl diphosphonate (MDP) or hydroxydiphosphonate (HDP), calcium salt analogues, and hematopoiesis can be graphically assessed using ⁵²Fe, ⁵⁹Fe, ^99mTc nanocolloid, and ^99mTc-labeled anti-NCA95 antibody. Bones are hardened with calcium salts and, under the influence of calcitonin, bone calcium is mobilized into general circulation to maintain homeostasis. Being closely integrated with other tissues in general calcium metabolism, bone serves as the largest reservoir of calcium in the human body (97%) (Williams et al. 1989). The mobilization of calcium from bone results in decalcification that occurs in various conditions such as immobilization, inflammation, arthritis, osteoporosis, renal osteodystrophy, and reflex sympathetic dystrophy. Actually, live bones are ceaselessly engaged with the deposition and removal of calcium salts in the form of bone production and résorption mediated through the activities of osteoblasts and osteoclasts. Altered calcium metabolism, either local or systemic, can be assessed using radiography, CT, MRI, scintigraphy, and neutron activation analysis. However, bone scintigraphy can uniquely image both anatomy and molecular or metabolic profile at the same time (Holms 1978; Smith 1986; Bahk 2000; Etchebehere et al. 2001). In addition, denatured muscle can also be imaged by ^99mTc-MDP or -HDP scan. Bone marrow is the largest hematopoietic organ in the human producing erythropoietic precursor cells, granulocytes, and reticuloendothelial cells. Each of these cells can be separately imaged using appropriate radiopharmaceuticals. Bone marrow scan will be discussed in detail under a separate section. From the view point of molecular nuclear medicine and for the sake of a categorical description, it seems warranted to classify skeletal disorders into two major groups. The first group consists of disorders that are associated with genetic imbalance or heredity and the second group consists of disorders that are mere histopathological entities in nature with no known association with genome problems. Disorders in the first group, clinically by far less common in occurrence than the second group, result from autosomal or sex chromosomal imbalance or mutations. Well known autosomal and chromosomal disorders include Turner syndrome, Klinefelter syndrome, and trisomy defects. Mucopolysaccharidoses and osteochondrodysplasias are other major groups of genetic disorders. The former disorders, caused by genetically determined deficiencies of lysosomal enzymes that degrade mucopo-lysaccharides (McAlister and Herman 1995), include Hurler’s disease, Hunter’s syndrome, and Morquio’s disease and the latter Marfan’s syndrome, osteopetrosis, osteogenesis imperfecta (Goldman 1995), multiple cartilaginous exostoses, and others. Certain skeletal disorders are known to be the result of the action of several different genes and hence referred to as polygenic disorders. Rheumatoid arthritis, ankylosing spondylitis, and Reiter’s syndrome belong to this category. These disorders can be assessed by antigen test, the HLA-B27 antigen in particular (Morris et al. 1974; Kahn 1988), and constitute excellent indications for bone scintigraphy (Kim et al. 1999; Bahk 2000).