Pharmacokinetic Analysis of Accumulation of Gluconic Acid Complexes with 99mTc and Mn(II) in Gliomas and Metastatic Brain Lesions, using Dynamic Magnetic Resonance Imaging and Single-Photon Emission Computed Tomography

Relevance: A promising direction for the successful development of diagnostic tomography is the creation of pairs of paramagnetic contrasts for MRI and radiopharmaceuticals for SPECT with identical biological and pharmacokinetic properties. Comparing the results of contrast-enhanced MRI and SPECT scans could provide then fundamentally new information. Purpose: To evaluate the imaging abilities of 99mTc-gluconate as an RFP for SPECT/CT, in comparison with Mn-gluconate (for paramagnetic contrast enhancement in MRI), in the course of creation of a new generation of diagnostic agents for combined SPECT/MRI studies of brain tumors. Material and methods: 99mTc-gluconate was obtained by labeling for 30 minutes, at room temperature above 25°C, 370‒540 MBq of Technetium ‒ 99m eluate in a volume of 2‒4 ml, from a 99Mo/99mTc generator, while the lyophilized labeling kit included 2.5 mg of gluconic acid, 0.10 mg of SnCl2×2H2O as a reducing agent, 7.5 mg sodium hydrophosphate dodecahydrate and 1.5 mg ascorbic acid. Mn(II)-gluconate was obtained in one step from manganese(II) oxide or carbonate and gluconic acid or sodium gluconate, with their mixing in molar amounts in a ratio of 1:2, dispersion and stirring in a ball mill for 20‒30 minutes, dissolution in saline solution, sterilization by microfiltration and obtaining 0.5 M solution of Mn(II)-gluconate, pH 6.5‒7.8, The study comprised the results of an examination of nine patients with low-grade (3‒4 degrees of anaplasia) brain gliomas, one patient with meningioma of the middle cranial fossa, and three patients with brain metastases (kidney, lung, and breast cancers). All underwent SPECT with 99mTc-gluconate on a Gemini dual-detector gamma camera (Technicare, USA), controlled by the Scinti 3.3 computer system (NPF Gelmos, Russia) after the injection of 370‒540 MBq of the RFP. A dynamic planar study was recorded after injection, for 20 minutes, with blood samples taken to assess the clearance of rfp. SPECT then included 64‒128 planar projections of 360° rotation detectors with a set of 50,000 pulses each, in a 64 × 64 matrix. The rate of absorption of rfp and paramagnetic substances by tumors and the indices (Tumor)/(Healthy tissue) were calculated. The rate of absorption of the drug by the tumor was calculated as the ratio of the concentration in the tumor tissue to the area under the concentration curve in the blood. Results: The rate of contrast absorption from blood to tumor was 6.72 ±2.01 (3.5; 12.1) ml/min/100 g for 99mTc-gluconate and 5.93 ± 2.95 (3.2; 10.1) ml/min/100 g for Mn-gluconate for peripheral gliomas, the correlation between them was highly reliable, as Y = ‒0,14 + 0,89×X (r = 0.89, p = 0.000372). The unaffected gray matter of the brain showed an order of magnitude lower absorption rate from the blood, respectively 0.20 ±0.09 (0.07; 0.41) ml/min/100 g of 99mTc-gluconate and 0.23 ± 0.12 (0.05; 0.49) ml/min/100 g for Mn-gluconate. Indexes (Tumor)/(Healthy tissue) were 15.2 ± 3.28 (11.19; 21.23) for 99mTc-gluconate and 11.28 ± 9.80 (2.4; 30.26) for Mn-gluconate, with the correlation equation Y = 0.74 + 0.67×X (r = 0.94, p = 0.00684), indicating the biological identity of these complexes. Conclusion: The results of the assessment of tumor accumulation of gluconic acid complexes with 99mTc- and Mn substantiate the possibility of wider use in neuro-oncology of rfp 99mTc-gluconate in SPECT and Mn-gluconate in MRI as a paramagnetic analogue of 99mTc-gluconate, with high affinity to brain tumors, and possibility of MRI/SPECT fused studies.