First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer

Abstract

Technetium-99m labelled red blood cells (99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). 99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3-di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with 99mTc at room temperature by simple addition of stannous ions and eluate of a 99mTc generator. After evaluation in mice and rabbits, two different 99mTc-DMP-HSA preparations - obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 - were tested in a volunteer and compared to 99mTc-RBCs. The blood time-activity curves of the three preparations were quite similar but both 99mTc-DMP-HSA preparations were excreted much less into the urine than 99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both 99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Preclinical assessment of Tc-99m labeled Nano colloid Liposomes as an Effective Blood Pool Radiopharmaceutical.

“…Verbeke et al (2,3) developed a dimercaptopropionyl-modified HSA and showed that it had superior in vivo stability when compared to a conventional kit of 99mTc-HSA in human volunteers. This in vivo stability was similar to that shown for 99mTc-liposomes in that there was good retention of the modified HSA in the bloodstream and low bladder activity.…”

“…Despite these positive features. Long-term storage of modified HSA may not be as reliable as 99mTc-liposomes due to oxidation of the sulfhydryl groups (2)(3)(4) .…”

“…Several strategies have been explored to develop blood-pool agents that are more effective than 99mTc-HSA and that do not rely on the use of autologous 99mTc-red cells. First, HSA has been modified by conjugation with 2,3dimercaptopropionyl before 99mTc labeling and shown to have greater in vivo (2,3) . A second potential cell-free blood-pool agent currently in preclinical testing consists of polylysine polymer conjugation of diethylenetriacetic acid (DTPA) for chelation of 99mTcand containing a polyethylene glycol (PEG) for increased circulation times (PEG 99mTc-DTPA polylysine polymer) (4) .…”