Radiolabeling a novel NOTA-adrenomedullin derivative via the Al18F approach

Objectives The 99mTc-labeled adrenomedullin derivative (PulmoBind) exhibits high potential as an imaging agent for pulmonary hypertension and pulmonary embolism. The present work describes various complexation experiments using the inexpensive DTPA as chelator to assess optimal conditions for radiolabeling a novel NOTA-adrenomedullin derivative via Al18F.

Methods A human adrenomedullin analog synthesized by solid phase was conjugated with NOTA using the NOTA-NHS ester. 18F was eluted from the small anion resin cartridge (MP-1) with NaCl 0.9%. 18F-complexation with DTPA was assayed in different conditions: Al-to-DTPA molar ratios, order of addition of reagents, and heating conditions. The Al18F-DTPA complex was analyzed by ITLC-SG with citric acid pH 1.6 as mobile phase. The NOTA-peptide (171 μM) in NaOAc 0.1M was radiolabeled with 18F (74-148 MBq) and AlCl3 (6.7 nmol) for 15 min at 100oC, pH 4. Using a similar approach, the Al19F-NOTA-peptide was synthesized. The resulting compounds were analyzed by HPLC (XBridge C18 3x150 mm 3.5 μm).

Results The NOTA-conjugated peptide was obtained in high purity (≍90%). High levels of 18F were eluted from the MP-1 cartridge in high concentration (50 μL). A high complexation yield (≍97%) for Al18F-DTPA was obtained with 1:30 Al-to-DTPA ratios by addition of [Al18F]2+ to DTPA in mild conditions, while lower yields were obtained when 18F was added to Al-DTPA complex in presence of low amounts of Al(III). Al18F- and Al19F-NOTA-peptide yielded 12% and 89%, respectively. Work is currently in progress.

Conclusions While the novel NOTA-adrenomedullin derivative was radiolabeled with Al18F in modest yields, the complexation with DTPA indicates that this process can be optimized to much better yields.