skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Design of site specific radiopharmaceuticals for tumor imaging. (Parts I and II)

Abstract

Part I. Synthetic methods were developed for the preparation of several iodinated benzoic acid hydrazides as labeling moieties for indirect tagging of carbonyl-containing bio-molecules and potential tumor-imaging agents. Biodistribution studies conducted in mice on the derivatives having the I-125 label ortho to a phenolic OH demonstrated a rapid in vivo deiodination. Part II. The reported high melanin binding affinity of quinoline and other heterocyclic antimalarial drugs led to the development of many analogues of such molecules as potential melanoma-imaging agents. Once such analogue iodochloroquine does exhibit high melanin binding, but has found limited clinical use due to appreciable accumulation in non-target tissues such as the adrenal cortex and inner ear. This project developed a new series of candidate melanoma imaging agents which would be easier to radio-label, could yield higher specific activity product, and which might demonstrate more favorable pharmacokinetic and dosimetric characteristics compared to iodochloroquine.

Authors:
Publication Date:
Research Org.:
Lehigh Univ., Bethlehem, PA (USA)
OSTI Identifier:
5817010
Resource Type:
Thesis/Dissertation
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 62 RADIOLOGY AND NUCLEAR MEDICINE; IODINE ISOTOPES; TISSUE DISTRIBUTION; RADIOPHARMACEUTICALS; CHEMICAL PREPARATION; BRAIN; MICE; NEOPLASMS; RADIOISOTOPE SCANNING; ANIMALS; BODY; CENTRAL NERVOUS SYSTEM; COUNTING TECHNIQUES; DISEASES; DISTRIBUTION; DRUGS; ISOTOPES; LABELLED COMPOUNDS; MAMMALS; NERVOUS SYSTEM; ORGANS; RODENTS; SYNTHESIS; VERTEBRATES; 400702* - Radiochemistry & Nuclear Chemistry- Properties of Radioactive Materials; 550601 - Medicine- Unsealed Radionuclides in Diagnostics

Citation Formats

Van Dort, M.E.. Design of site specific radiopharmaceuticals for tumor imaging. (Parts I and II). United States: N. p., 1983. Web.
Van Dort, M.E.. Design of site specific radiopharmaceuticals for tumor imaging. (Parts I and II). United States.
Van Dort, M.E.. 1983. "Design of site specific radiopharmaceuticals for tumor imaging. (Parts I and II)". United States. doi:.
@article{osti_5817010,
title = {Design of site specific radiopharmaceuticals for tumor imaging. (Parts I and II)},
author = {Van Dort, M.E.},
abstractNote = {Part I. Synthetic methods were developed for the preparation of several iodinated benzoic acid hydrazides as labeling moieties for indirect tagging of carbonyl-containing bio-molecules and potential tumor-imaging agents. Biodistribution studies conducted in mice on the derivatives having the I-125 label ortho to a phenolic OH demonstrated a rapid in vivo deiodination. Part II. The reported high melanin binding affinity of quinoline and other heterocyclic antimalarial drugs led to the development of many analogues of such molecules as potential melanoma-imaging agents. Once such analogue iodochloroquine does exhibit high melanin binding, but has found limited clinical use due to appreciable accumulation in non-target tissues such as the adrenal cortex and inner ear. This project developed a new series of candidate melanoma imaging agents which would be easier to radio-label, could yield higher specific activity product, and which might demonstrate more favorable pharmacokinetic and dosimetric characteristics compared to iodochloroquine.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = 1983,
month = 1
}

Thesis/Dissertation:
Other availability
Please see Document Availability for additional information on obtaining the full-text document. Library patrons may search WorldCat to identify libraries that hold this thesis or dissertation.

Save / Share:
  • Procedures were developed to label analogues of the nonsteroidal estrogen hexestrol with /sup 75/Se. Labeling was accomplished by substitution of divalent selenium for methylene. 1-Iodo-2,3-diphenylpentane and 1-iodo-2,3-bis(4-methoxyphenyl)pentane were synthesized and converted to their corresponding diselenides using NaH/sup 75/Se as nucleophile. The NaH/sup 75/Se was generated from (/sup 75/Se)selenious acid using NaBH/sub 4/ at pH 6.0. 1-(/sup 125/I)iodo-2,3-bis(4-methoxyphenyl)pentane was obtained from 2,3-bis(4-methoxyphenyl)pentane was obtained from 2,3-bis(4-methoxyphenyl)pentylmethanesulfonate using Na/sup 125/I in refluxing acetone. The cyclopropyl compound 1,1-dichloro-2,3-diphenylcyclotpropane was labeled with /sup 125/I at the 4-position on the aromatic ring. Labelling was accomplished by reacting 2,1-stilbeneazopyrrolidine synthesized from 4-nitrostilbene with Na/sup 125/I. Biodistributionmore » studies in mature and immature female Sprague Dawley rats showed that the 1-methyl-(/sup 75/Se)seleno-2,3-bis(4-methoxyphenyl)pentane obtained slightly higher uterine-to-blood ratios and uterine tissue concentrations than did the other compounds.« less
  • Radioiodinated analogs of the naturally-occurring alkyl lysophospholipid (ALP) were designed and synthesized for evaluation as potential tumor-specific imaging agents. The five iodinated ALP analogs synthesized were rac-1-O-(12-(m-iodophenyl)dodecyl)glycero-3-phosphocholine, ET-12IP-OH; rac-1-O-(12-(m-iodophenyl)dodecyl)-2-O-methylglycero-3-phosphocholine, ET-12IP-OMe; rac-1-O-(12-(m-iodophenyl)dodecyl)propane-1,3-diol-3-phosphocholine, ET-12IP-H; rac-1-O-hexadecyl-2-O-(m-iodobenzoyl)-glycero-3-phosphocholine, ET-16-IBz and rac-1-O-hexadecyl-2-O-(m-iodobenzyl)-glycero-3-phosphocholine, ET-16-IBn. Four analogs, ET-12IP-OMe, ET-12IP-H, ET-16-IBz and ET-16-IBn were radiolabeled with iodine-125 in moderate yields via an isotope exchange procedure. ({sup 125}I)ET-12IP-OMe, ({sup 125}I)ET-12IP-H and ({sup 125}I)ET-16-IBz were evaluated in tissue distribution (TD) studies involving both normal and tumor-bearing rats. The tumor chosen for this study was the Walker 256 sarcoma which was implanted in the thigh. Based upon the TD results and themore » tumor to nontumor ratios, ({sup 125}I)-ET-12IP-OMe was selected for scintigraphic studies with rats bearing the Walker 256 sarcoma. Twenty-four hours following administration of the radiolabeled ALP analog, external imaging with a gamma-camera clearly delineated the tumor.« less
  • The need of a dopamine-receptor based radiopharmaceutical for brain imaging is apparent. If such an agent is made available to physicians, it could provide means for detecting brain tumors, and diagnose such mental disorders as parkinsonism, schizophrenia and psychosis. Currently, such agents are yet to be discovered. Procedures were developed to synthesize and label four ergoline derivatives which could potentially exhibit affinity to dopamine receptors. Labelling with /sup 125/I was accomplished in some cases by displacing a suitably positioned leaving group with /sup 125/I-anion, while in other cases iodine exchange procedures were utilized. Formulations of the labeled derivatives were achievedmore » via the formation of their water soluble tartarate salts. Biodistribution studies in mature Sprague-Dawley rats showed that of the four radioactive compounds injected, the highest uptake in the brain and adrenals was achieved with 8 ..beta..-(I-125)-iodomethyl-6-propylergoline. In addition, high target/nontarget ratios were obtained with the above mentioned compound. On the other hand, the least brain and adrenal uptake as well as the lowest target/nontarget ratios were exhibited by 8 ..beta..-(I-125)-(p-iodobenzenesulfonyl)-lysergol presumably due to its in-vivo instability. A comparative biodistribution study for ergoline derivatives and N-isopropyl-(I-123)-p-iodoamphetamine was conducted. The biodistribution studies showed that the brain to blood ratio for the ergoline derivative 8 ..beta..-(I-125)-iodomethyl-6-propylergoline to be very close to that for /sup 125/I-IMP at 1 minute after dose administration. However after 15 minutes the brain/blood ratio of compound XLVI was half the value of /sup 123/I-IMP. Different mechanisms of brain influx and efflux are known to occur with the amphetamine and ergoline derivatives.« less
  • A new method of radiolabeling proteins has been explored that involves the coupling of a metal chelating agent, diethylenetriaminepentaacetic acid (DTPA), to proteins in aqueous solution through the use of the DTPA bisanhydride. Each derivatized protein was then radiolabeled with an appropriate carrier-free metallic radionuclide. The proteins examined in this investigation were human serum albumin, human and canine fibrinogen, bovine and human nonspecific gamma globulin, and antibodies to carcinoembryonic antigen (CEA). The two different anti-CEA antibodies chosen for this study were affinity-purified baboon anti-human CEA and monoclonal murine anti-human CEA. The radionuclides were gallium-67, indium-111, and yttrium-90. With /sup 111/In,more » the method was shown to successfully radiolabel each of the model proteins without significantly altering their in vitro or in vivo behavior.« less