/sup 99m/Tc-labeled nucleotides as tumor-seeking radiodiagnostic agents

Journal Article · Wed Feb 01 04:00:00 EST 1984 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.81.3.918· OSTI ID:5835557

Elmaleh, D R; Zamecnik, P C; Castronovo, Jr, F P; Strauss, H W; Rapaport, E

Several lines of human tumor cells in monolayer and soft agar cultures allow permeation of low levels of adenine nucleotides through their plasma membranes, while, in general, untransformed cells do not incorporate adenine nucleotides into their cellular pools without prior degradation of the nucleotides to adenosine. This study determined the uptake of /sup 99m/Tc-radiolabeled chelated forms of adenine nucleotides, /sup 99m/Tc-Ap/sub 4/A (diadenosine 5',5''',P/sub 1/,P/sub 4/-tetraphosphate) and /sup 99m/Tc-ATP chelates as radiodiagnostic agents suitable for the in vivo detection of tumors by radionuclide imaging. Biodistribution studies revealed that Ap/sub 4/A accumulated preferentially in RT-24 tumors implanted in rats and that V2 carcinoma implanted in rabbits could be readily visualized by in vivo imaging. The biodistribution at various time points showed increased tumor-to-muscle ratios after /sup 99m/Tc-Ap/sub 4/A or /sup 99m/Tc-ATP injections when compared with a nonspecific marker of the extracellular fluid space, /sup 99m/Tc-labeled diethylenetriaminepentaacetic acid and with an agent known to localize in some tumors, /sup 67/Ga-labeled citrate. Studies of ectoenzymatic activities of virus-transformed animal cells and their untransformed counterparts in monolayer cultures showed marked decreases in the ectoenzymatic activities that degrade Ap/sub 4/A in the transformed cells. Incorporation of en bloc (/sup 3/H, /sup 32/P)Ap/sub 4/A into cellular acid-soluble nucleotide pools of certain transformed cells was observed. Normal untransformed cells incorporated the radioactive label only by prior degradation to (/sup 3/H)adenosine and /sup 32/P/sub i/. 19 references, 2 figures, 3 tables.

• Research Organization: Massachusetts General Hospital, Boston
• OSTI ID: 5835557
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 81:3; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL LOCALIZATION
BIOLOGICAL MARKERS
CARBOXYLIC ACID SALTS
CITRATES
COMPARATIVE EVALUATIONS
DATA
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DISEASES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
EXPERIMENTAL DATA
GALLIUM 67
GALLIUM ISOTOPES
HOURS LIVING RADIOISOTOPES
IMAGES
INFORMATION
INTERMEDIATE MASS NUCLEI
ISOMERIC NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LABELLING
LIGHT NUCLEI
MAMMALS
MAN
NEOPLASMS
NUCLEI
NUCLEOTIDES
NUMERICAL DATA
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
RABBITS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
RODENTS
TECHNETIUM 99
TECHNETIUM ISOTOPES
TISSUE DISTRIBUTION
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES
YEARS LIVING RADIOISOTOPES