The strength of Nuclear Medicine lies in the ability to differentiate the disease states based on physiological and biochemical changes reflected in blood flow, receptor density and metabolic rate. The potential use of Nuclear Medicine Methodology to diagnose diseases on functional basis instead of anatomy has been discussed since the inception of Nuclear Medicine. In the last two to three years, we have seen more convincing evidence that Nuclear Medicine is now best equipped to pioneer a new trend in Medicine termed "Molecular Medicine" through diagnosis of diseases at the molecular level. One example cited by Wagner (JNM 1994;35:13N-26N)is In-111 labeled octreotide which binds to somatostatin receptor, thereby differentiating endocrine tumors based on the expression of somatostatin receptor.
Recent advances of biotechnology such as hybridoma technology and genetic engineering have made it possible to produce various peptides and monoclonal antibodies which bind to specific receptors and tumor antigens. With a combination of different models of imaging such as metabolic, receptor and antigen imaging using newly developed radiobiologics, we are now at a treshhold of detecting diseases at the molecular level. At the Society of Nuclear Medicine held in Orlando this summer, several examples were shown:F-18 FDG differentiated benign pulmonary nodules from malignant lung cancer. A combination of radiolabeled octreotide and vasoactive intestinal peptide(VIP) helped differentiate pancreatic tumors based on expressions of receptors specific for these peptides;adenocarcinoma of pancreas is known to express VIP receptors whereas it does not express somatostatin receptors.
The trend in radiopharmaceutical development surveyed through the presentations at the Society indicated that a quarter of the presentations were in Oncology, with similar numbers in Cardiology and
Neurogy. Other interesting trend is the use of radiopharmaceuticals for therapy such as bone pain palliation and radioimmunotherapy. There was a sudden surge in the number of presentations in Oncology this year, 42% increase from last year. This elevated.,., activity in Oncology was due to the active research - o metabolic and receptor imaging using non-anti-4 body related agents such as FDG and peptides, su gesting that Oncology field is leading the trend fogs r 4 "Molecular Medicine". The trend in radiopha rmaceutical development was also reflected in the frequency of radionuclides used for the studies. Tc99m was used in the highest number with 367 pa pefollowed by F-18(166), 1-123(81), C-11(73), In-111 (68), 0-15(54), 1-131(46) and 1-125(32). Tc-99m is still the most popular radionuclide used in Nuclear Medicine and there is urgent need to develop Tc-99m labeling methods for radio-biologics such as Tc-99m - labeled peptides an single chain proteins containing an antigen-binding site. The active use of FDG and octreotide in Oncology boosted the number of F-18 and In-111 papers this year. J,
The major aim of my presentation today is to discuss about the important criteria for matching radionuclides and biologics when radiopharmaceuticals are developed. the important physical and chemical parameters are size, polarity, charge, stability, physical half life and biological half life."-.I
would like to present the radiolabeling of monoclonal antibodies as an example and show the sequential
steps required for the development of these
radiolabeled biologics.
The potential for hybridoma technology to produce
monoclonal antibodies directed against various anti
genic epitopes of target antigens has made
radiolabeled antibodies one of the most actively pur
sued agents in scintigarphic detection of lesions in
Oncological, Cardiological and Hematological Nuclear
the reduced Tc-99m and stannous ion (reducing agent) in a soluble form but transfer Tc-99m to MAG3 when the mercapto group of MAG3 is generated. Using a benzoyl group as a mercapto protect
ing ing group and glucarate as a transchelating agent,]´ we have successfully labeled a Bz-MAG3 conjugated single chain protein.
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