Pj. Blower et al., PENTAVALENT RE-188 DIMERCAPTOSUCCINIC ACID FOR TARGETED RADIOTHERAPY - SYNTHESIS AND PRELIMINARY ANIMAL AND HUMAN STUDIES, European journal of nuclear medicine, 25(6), 1998, pp. 613-621
Pentavalent rhenium-188 dimercaptosuccinic acid [Re-188(V)DMSA] is a b
eta-emitting analogue of Tc-99m(V)DMSA, a tracer that is taken up in a
variety of tumours and bone metastases. The aim of this study was to
develop the kit-based synthesis of the agent on a therapeutic scale, t
o assess its stability in vivo, and to obtain preliminary biodistribut
ion and dosimetry estimates, prior to evaluation of its potential as a
targeted radiotherapy agent. The organ distribution of Re-188 in mice
was determined 2 h after injection of 3 MBq Re-188(V)DMSA prepared fr
om eluate from a W-188/Re-188 generator. Three patients with cancer of
the prostate and three with cancer of the bronchus, all with bone met
astases confirmed with a standard Tc-99m-hydroxymethylene diphosphonat
e (Tc-99m-HDP) scan, were given 370 MBq Re-188(V)DMSA and imaged at 3
h and 24 h using the 155-keV gamma-photon (15%). Blood and urine sampl
es were collected to determine clearance and to analyse the speciation
of Re-188. Organ residence times were estimated from the scans, and u
sed to estimate radiation doses using MIRDOSE 3. In mice,Re-188(V)DMSA
was selective for bone and kidney. In patients, it showed selectivity
for bone metastases (particularly those from prostate carcinoma) and
kidney, but uptake in normal bone was not significantly greater than i
n surrounding soft tissues. Of the normal tissues the kidneys received
the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongl
y reminiscent of 99mTc(V)DMSA scans in similar patients. High-performa
nce liquid chromatography analysis of blood and urine showed no eviden
ce of Re-188 in any chemical form other than Re-188(V)DMSA up to 24 h.
In conclusion, Re-188(V)DMSA and its Re-186 analogue warrant further
clinical assessment as generator/kit-derived agents for treatment of p
ainful bone metastases. These agents should also be assessed in medull
ary thyroid carcinoma and other soft tissue tumours which have been sh
own to accumulate Tc-99m(`V)DMSA.