Abstract
The radioisotopes
186Re and
188Re have been extensively investigated for various forms of radiotherapy due to their useful and high-abundance β particle emissions, low-abundance and imageable γ-rays, and chemical resemblance to technetium. In addition,
188Re is available in no-carrier-added (NCA) form from long lived W-188 generators, whereas
186Re can be produced in large quantities from reactors, although not in NCA form. However, NCA
186Re can be produced on a cyclotron by a (
p,
n) reaction on
186W. The purpose of this study was to compare labeling of the peptide bombesin with these three forms of rhenium radioisotopes.
Cyclotron-produced NCA
186Re was separated radiochemically from enriched
186W (96.9%) targets using high-purity methyl ethyl ketone (MEK). The resulting
186Re-MEK was then loaded onto a small alumina column to separate the resulting NCA
186Re from any remaining
186W. The experimental levels of impurities associated with
186Re at the end of the separation process were found to be 5.7×10
−6 Ci of
182Re (0.57%,
t
1/2=12.7 h) and 1.283×10
−5 Ci of
182mRe (1.28%,
t
1/2=2.67 days). The radionuclidic purity of the separated
186Re was found to be 99.6%, whereas the chemical identity was determined by reversed phase high-performance liquid chromatography (RP-HPLC) to be perrhenate (
186ReO
4
−). Generator-produced
188ReO
4
− from a
188W/
188Re generator (Oak Ridge National Laboratory) and CA
186ReO
4
− produced from a
185Re(
n,
γ)
186Re reaction at the University of Missouri Research Reactor (MURR) were used for comparison with the NCA
186Re in subsequent studies.
N
3S-5-Ava-BBN(7–14)NH
2 conjugates provide flexibility for designing
186,188Re-labeled conjugates that retain high in vitro and in vivo specificity targeting of GRP receptor-expressing cells. This study showed that the N
3S-5-Ava-BBN(7–14)NH
2 could be labeled with
186,188Re following the preconjugation, postmetallation approach. The
186,188Re
VO-N
3S-5-Ava-BBN(7–14)NH
2 complexes were found to form stable complexes following the reduction of perrhenate (Re
VIIO
4
−) with stannous chloride at room temperature, as verified by HPLC and stability studies. The radiolabeling yield was found to be >90%. The HPLC chromatograms of
186,188Re-N
3S-5-Ava-BBN(7–14)NH
2 complexes revealed two peaks for each conjugate, reflecting the presence of
syn- and
anti-isomers, which were resolvable by HPLC but re-isomerized on separation. The biodistribution studies showed that the compounds were excreted through the renal and hepatobiliary systems and demonstrated receptor-specific uptake with an average pancreas accumulation of 8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked pancreatic uptake and further reflects the high specificity this conjugate has for the GRP receptors. At low levels of radioactivity, radiolysis effects were not observed. Scale-up may or may not elicit this effect, particularly for the higher energy β emitter
188Re. The biodistribution studies demonstrated that the CA and NCA
186,188Re conjugates behaved similarly, raising the question of whether NCA
186,188Re is necessary for specific tumor receptor targeting.