Quantitative analysis of phantom studies of 111In and 68Ga imaging of neuroendocrine tumours.

BACKGROUND: Nuclear medicine imaging of neuroendocrine tumours is performed either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using 68Ga-radiolabelled somatostatin analogs. These imaging techniques will give different image quality and different detection thresholds for tumours, depending on size and activity uptake. The aim was to evaluate the image quality for 111In-SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for different source-to-background activity ratios. The accuracy of quantification of lesion volume and activity was also investigated to develop an objective evaluation for radionuclide therapy eligibility. The phantom study was performed using the NEMA IEC Body Phantom with six hot spheres having inner diameters of 10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to-background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1. Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the liver and spleen. Clinical acquisition and reconstruction protocols were applied. Line profiles were drawn to evaluate the smallest detectable volume within a given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs adapted to the background and CT-based ROIs were obtained for all SBRs and sphere diameters, allowing for quantification. RESULTS: The 10-mm sphere was not possible to detect in SPECT images. It was detectable in PET images for SBRs of 2.5:1 and higher. In a background corresponding to the activity uptake in the liver, spheres larger than 22-37 mm were detectable in the 111In-SPECT images and spheres larger than 13-22 mm were detectable in the 68Ga-PET images. The maximum activity concentration was accurately quantified for spheres larger than 22 mm in the PET images; however, the quantification was impaired by sphere size and background activity. CONCLUSIONS: It was not possible to detect the 10-mm sphere in any of the SPECT images. In a background corresponding to the activity uptake in the liver, spheres larger than approximately 30 mm were visible in the 111In-SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga-PET images. Sphere diameter and background activity strongly affect the possibility of a correct quantification.

Clinical dosimetry in the treatment of bone tumors: old and new agents.

Treatment of multisite, sclerotic bone metastases is successfully performed by radionuclide therapy. Pain palliation is the most common aim for the treatment. Two radiopharmaceuticals are currently approved by the European Medicines Agency ((153)Sm-EDTMP and (89)Sr-Cl2) whilst other radiopharmaceuticals are at different stages of development, or are approved in some European countries ((186)Re-HEDP, (117)Snm-DTPA and (223)Ra-Cl2). The tissues at risk for the treatment are bone marrow and normal bone. A review of the methods applied for dosimetry for these tissues and for tumours is performed, including the calculation of S values (the absorbed dose per decay) and optimal procedures on how to obtain biodistribution data for each radiopharmaceutical. The dosimetry data can be used to individualise and further improve the treatment for each patient. Dosimetry for radionuclide therapy of bone metastases is feasible and can be performed in a routine clinical practice.

Comparison of 125I- and (111)In-labeled monoclonal antibody BR96 for tumor targeting in combination with extracorporeal immunoadsorption.

Extracorporeal whole blood immunoadsorption (ECIA) accelerates the clearance of radiolabeled monoclonal antibodies (mAbs) without significantly affecting tumor uptake by removing the excess of these mAbs from the blood, thus increasing tumor:normal tissue (T:N) ratios. The present study is focused on comparing the capacity of ECIA in tumor targeting with the same mAb (chiBR96-biotin) labeled with either (111)In or 125I. Forty-five Brown Norwegian rats with syngeneic rat colon carcinoma isografted both in liver and intramuscularly were used. chiBR96 is a highly tumor-specific mAb directed against the Lewis-type antigen. ECIA of whole blood was started 15 h after the injection of 125I- or (111)In-labeled BR96-biotin. The procedure lasted for 2 h and was repeated for (111)In-labeled BR96-biotin in a few rats after 3 or 24 h. ECIA reduced the whole body activity by the same magnitude (between 39% and 52%), irrespective of whether (111)In- or 125I-labeled chiBR96 was used. A similar observation was also made for the reduction in blood radioactivity after ECIA (79-94%). Time-activity curves during ECIA showed that the major reduction (approximately 85%) in blood radioactivity occurred during the first 45-60 min. Repeating the ECIA with (111)In-BR96 caused only an additional minimal reduction of blood activity, whereas a further reduction of whole body activity of 14-20% was achieved. The T:N uptake ratios were significantly enhanced immediately after ECIA with (111)In- or 125I-labeled chiBR96. Due to greater accumulation of (111)In-BR96 in tumors, a long-term improvement in T:N ratios was obtained after ECIA compared with 125I-labeled BR96. Our results therefore indicate that (111)In/(90Y)-labeled BR96-biotin could be more advantageous than 125I/131I for radioimmunotargeting/radioimmunotherapy in combination with ECIA due to better activity retention by the tumor.

Extracorporeal immunoadsorption compared to avidin chase: enhancement of tumor-to-normal tissue ratio for biotinylated rhenium-188-chimeric BR96.

UNLABELLED: Based on the biodistribution and kinetics of biotinylated 188Re-chimeric BR96 (chiBR96), the enhancement of the tumor-to-normal tissue (T/N) radioactivity ratio using extracorporeal immunoadsorption (ECIA) was evaluated and compared with that of avidin "chase" in colon carcinoma-isografted Brown Norwegian rats. METHODS: Extracorporeal immunoadsorption (ECIA) was performed 6 or 12 hr after intravenous administration of biotinylated 188Re-chiBR96. Radioactivity redistribution was investigated just after ECIA [8 or 14 hr postinjection of the antibody] and 40 or 34 hr after ECIA performance (48 hr postinjection). Avidin was administered intraperitoneally at 6 hr postinjection. Tumor radioactivity uptake and T/N activity ratios of biotinylated 188Re-chiBR96 were compared using ECIA and avidin chase and were also compared with controls. RESULTS: Both ECIA and avidin chase can rapidly increase the radioactivity tumor-to-blood ratio without significantly interfering with the tumor uptake. ECIA at 8 hr postinjection increased the T/N ratios in blood-rich tissues, such as liver and bone marrow, from 6 and 8 to 10 and 18, respectively. Corresponding T/N ratios at 14 hr increased from 9 and 10 to 24 and 36. In contrast, when avidin chase was used, there were no T/N improvements, except in blood. Moreover, avidin chase caused a significant accumulation of radioactivity in the liver. CONCLUSION: The ECIA approach, with direct removal of unbound circulating biotinylated 188Re-chiBR96, thus can rapidly improve and maintain T/N ratios without overloading the liver with radioactivity, in contrast to avidin chase.