Production and clinical evaluation of 99mTc-octreotide

Full text: Due to advantages of 99m-Tc labelled radiopharmaceuticals we examined the feasibility of producing 99m-Tcoctreotide in our laboratory and compare the results with 111-In-octreotide in the same patients. Keeping constant amount of components without exceeding amount of the peptide used, preparation of 99m-Tc-ethylendiaminediacetic- acidhydrazinonicotinamide-D-Phe1,Tyr3-octreotide (99m-Tc EDDA/HYNIC-TOC) was achieved. Radiochemical purity was tested using high-pressure liquid chromatography for 24 hours. In vitro stability testing of the product showed that radiochemical purity remained above 95% for 24 hours and the radiopharmaceutical was found suitable for human use. 5 - 10 μg of the peptide labelled with 550-650 MBq of 99m-Tc was prepared for each patient. 32 patients with clinically suspicious or confirmed carcinoid were investigated with 550 - 650 MBq 99m-Tcoctreotide prepared in our laboratory followed by 110 MBq 111-In-octreotide (Octreoscan, Mallinkrodt). Whole body scintigraphy and abdominal SPECT were performed 4 and 20 hrs after injection of respective radiopharmaceutical. In all patients both studies were acquired within 5 days. All patients gave informed consent for the study as required by Ethics committee. No abnormal tracer uptake was seen anywhere in the body in 12 patient with either of the radiopharmaceuticals. These were used to assess normal distribution of both radiopharmaceuticals. Normal accumulation was seen in case of both radiopharmaceuticals in the spleen, kidneys, liver and gallbladder. Biliary activity was seen in the gut in patients that were not well prepared for the study. There was significantly less activity seen in the kidneys in case of 99m-Tc-octreotide. This could be explained by higher hydrophilicity of the 99m-Tc-EDDA/HYNEC-TOC molecules as compared with 111-In-DTPA-octreotide. 20 patients with confirmed carcinoids showed abnormal uptake but without any difference in distribution of the two radiopharmaceuticals. Number, size and activity in the lesions were equal for both radiopharmaceuticals. All lesions were seen at 4 as well as 20 hrs. post injection images. Using 111-Inoctreotide some lesions between the kidneys were seen with less confidence on SPECT images as compared with 9m-Tc-octreotide. Lesions inside the liver were also determined more confidently on 99m-Tc-octreotide SPECT reconstructions, due to better count statistics. Octreotide can be labelled as D-Phe1-octreotide with 111-In using DTPA as chelator and as D-Phe1, Tyr3-octreotide with 99m-Tc using ethylendiaminediacetic acid hydrazine- nicotinamide (99m-Tc EDDA/HYNIC-TOC). 111-In-octreotide is commercially available, has long half-life, which allows for repeated imaging up to 72 hrs post injection. Extensive experience with this radiopharmaceutical has been accumulated over several years. However, it has sub optimal energy for imaging, high absorbed dose for the patients, is expensive and is not readily available. Tc-99m octreotide on the other hand profits from nearly ideal imaging characteristics, is inexpensive and always available if produced locally, but allows imaging maximally 24 hrs post injection. Three-dimensional structure of 99m-Tc-octreotide is not exactly the same as of 111-In octreotide. Appropriate low amount of the octreotide can be labelled with high enough 99m-Tc activity to allow good image resolution also using SPECT up to 24 hrs. From our study, it appears that labelling of the peptide is stable not only in vitro but also in vivo. Diagnosis, localization and tumour spread can be determined using 99m-Tc-EDDA/HYNEC-TOC at least as confidently as using 111-In-octreotide. Its advantages are availability, low cost, decreased absorbed dose for the patients and high quality of scintigraphic images. (author)