Introduction
In this study, novel 99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (99mTc-ISboroxime-N3: R = IS; 99mTc-MPboroxime-N3: R = MP; 99mTc-PAboroxime-N3: R = PA; 99mTc-PYboroxime-N3: R = PY; and 99mTc-Uboroxime-N3: R = 5U) were evaluated as heart imaging agents.
Methods
Complexes [99mTc(N3)(CDO)(CDOH)2B-R] (R = IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN3 and [99mTcCl(CDO)(CDOH)2B-R]. Biodistribution and imaging studies were carried out in Sprague–Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention.
Results
99mTc-ISboroxime-N3, 99mTc-PYboroxime-N3 and 99mTc-Uboroxime-N3 were prepared with high RCP (93–98%) while the RCP of 99mTc-MPboroxime-N3 and 99mTc-PAboroxime-N3 was 80–85%. The myocardial retention curves of 99mTc-ISboroxime-N3, 99mTc-PYboroxime-N3 and 99mTc-Uboroxime-N3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6 ± 0.4 min for 99mTc-ISboroxime-N3, 0.7 ± 0.1 min for 99mTc-PYboroxime-N3 and 0.9 ± 0.4 min for 99mTc-Uboroxime-N3. The 2-min heart uptake from biodistribution studies followed the ranking order of 99mTc-ISboroxime-N3 (3.60 ± 0.68%ID/g) > 99mTc-PYboroxime-N3 (2.35 ± 0.37%ID/g) ≫ 99mTc-Uboroxime-N3 (1.29 ± 0.06%ID/g). 99mTc-ISboroxime-N3 had the highest 2-min heart uptake among 99mTc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0–5 min for 99mTc-ISboroxime-N3.
Conclusion
Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [99mTc(N3)(CDO)(CDOH)2B-R]. Among the radiotracers evaluated in SD rats, 99mTc->ISboroxime-N3 has the highest initial heart uptake with the heart retention comparable to that of 99mTc-Teboroxime. 99mTc-ISboroxime-N3 is a promising alternative to 99mTc-Teboroxime for SPECT MPI.
Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with (131)I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that (131)I-labeled BLMG ((131)I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of (131)I-BLM and (131)I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that (131)I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, (131)I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.
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