Convenient Formulation of 68Ga-BPAMD Patient Dose Using Lyophilized BPAMD Kit and 68Ga Sourced from Different Commercial Generators for Imaging of Skeletal Metastases.

PURPOSE: 68Ga-BPAMD has recently emerged as one of the preferred radiopharmaceuticals for imaging of bone lesions due to its ability to produce high-resolution images and uncomplicated availability of 68Ga, a positron emission tomography (PET) radionuclide, from commercial 68Ge/68Ga generators. The primary objective of this work is to develop freeze-dried BPAMD kit, for the easy and convenient formulation of 68Ga-BPAMD patient dose at the hospital radiopharmacy. In addition, the kit should be compatible with 68Ga, eluted using HCl of various molarities from the 68Ge/68Ga generators sourced from different suppliers. PROCEDURES: Freeze-dried BPAMD kit, comprising 50 µg of BPAMD and 150 mg of HEPES, was prepared and evaluated using 68Ga eluted from three different 68Ge/68Ga generators. Radiochemical purity (RCP) of 68Ga-BPAMD was determined by both thin-layer chromatography and high-performance liquid chromatography studies. The maximum volume of 68Ga, which can be added in the kit, was determined. The biological behavior of 68Ga-BPAMD, prepared using the freeze-dried kit, was evaluated by both in vitro and in vivo studies. Clinical studies were also performed in limited number of patients suffering from metastatic bone cancer. RESULTS: 68Ga-BPAMD could be prepared with >95% RCP using the freeze-dried BPAMD kit and 68Ga eluted from 68Ge/68Ga generators obtained from three different suppliers. 68Ga-BPAMD, prepared using the freeze-dried kit, exhibited adequate serum stability and ∼91% binding with the hydroxyapatite particles. Biodistribution studies in normal Wistar rats exhibited selective uptake of the agent in skeleton and fast clearance of the nonaccumulated activity through urinary route. Clinical studies in cancer patients showed excellent accumulation of the agent in bone lesions. CONCLUSION: The preliminary studies exhibited the potential of the developed BPAMD kit toward its utilization for the PET scanning of skeletal metastases.

Biodistribution, pharmacokinetics, and organ-level dosimetry for 188Re-AHDD-Lipiodol radioembolization based on quantitative post-treatment SPECT/CT scans.

BACKGROUND: Rhenium-188-labelled-Lipiodol radioembolization is a safe and cost-effective treatment for primary liver cancer. In order to determine correlations between treatment doses and patient response to therapy, accurate patient-specific dosimetry is required. Up to date, the reported dosimetry of 188Re-Lipiodol has been based on whole-body (WB) planar imaging only, which has limited quantitative accuracy. The aim of the present study is to determine the in vivo pharmacokinetics, bio-distribution, and organ-level dosimetry of 188Re-AHDD-Lipiodol radioembolization using a combination of post-treatment planar and quantitative SPECT/CT images. Furthermore, based on the analysis of the pharmacokinetic data, a practical and relatively simple imaging and dosimetry method that could be implemented in clinics for 188Re-AHDD-Lipiodol radioembolization is proposed. Thirteen patients with histologically proven hepatocellular carcinoma underwent 188Re-AHDD-Lipiodol radioembolization. A series of 2-3 WB planar images and one SPECT/CT scan were acquired over 48 h after the treatment. The time-integrated activity coefficients (TIACs, also known as residence-times) and absorbed doses of tumors and organs at risk (OARs) were determined using a hybrid WB/SPECT imaging method. RESULTS: Whole-body imaging showed that 188Re-AHDD-Lipiodol accumulated mostly in the tumor and liver tissue but a non-negligible amount of the pharmaceutical was also observed in the stomach, lungs, salivary glands, spleen, kidneys, and urinary bladder. On average, the measured effective half-life of 188Re-AHDD-Lipiodol was 12.5 ± 1.9 h in tumor. The effective half-life in the liver and lungs (the two organs at risk) was 12.6 ± 1.7 h and 12.0 ± 1.9 h, respectively. The presence of 188Re in other organs was probably due to the chemical separation and subsequent release of the free radionuclide from Lipiodol. The average doses per injected activity in the tumor, liver, and lungs were 23.5 ± 40.8 mGy/MBq, 2.12 ± 1.78 mGy/MBq, and 0.11 ± 0.05 mGy/MBq, respectively. The proposed imaging and dosimetry method, consisting of a single SPECT/CT for activity determination followed by 188Re-AHDD-Lipiodol clearance with the liver effective half-life of 12.6 h, resulted in TIACs estimates (and hence, doses) mostly within ± 20% from the reference TIACs (estimated using three WB images and one SPECT/CT). CONCLUSIONS: The large inter-patient variability of the absorbed doses in tumors and normal tissue in 188Re-HDD-Lipiodol radioembolization patients emphasizes the importance of patient-specific dosimetry calculations based on quantitative post-treatment SPECT/CT imaging.

Radiochemical studies, pre-clinical investigation and preliminary clinical evaluation of 170Tm-EDTMP prepared using in-house freeze-dried EDTMP kit.

The objective of the present work is to formulate 170Tm-EDTMP using an in-house freeze-dried EDTMP kit and evaluate its potential as a bone pain palliation agent. Patient dose of 170Tm-EDTMP was prepared with high radiochemical purity using the lyophilized kit at room temperature within 15min. Pre-clinical evaluation in normal Wistar rats revealed selective skeletal accumulation with extended retention. Preliminary clinical investigation in 8 patients with disseminated skeletal metastases exhibited selective uptake in the bone and retention therein for a long duration.

Formulation, preclinical evaluation, and preliminary clinical investigation of an in-house freeze-dried EDTMP kit suitable for the preparation of 177Lu-EDTMP.

OBJECTIVE: The objective of the present work was to develop a freeze-dried ethylenediaminetetramethylene phosphonic acid (EDTMP) kit, suitable for the convenient and single-step preparation of (177)Lu-EDTMP, which is currently being evaluated as a promising radiopharmaceutical for providing palliative care to patients suffering from skeletal metastases and to assess the potential of the agent in human patients. EXPERIMENTAL: Lyophilized EDTMP kits having identical composition with Quadramet(®) were prepared using EDTMP, NaOH, and anhydrous CaCO3. The (177)Lu-EDTMP patient dose was prepared by incubating the kit materials dissolved in 1 mL of water for injection and (177)LuCl3, produced in-house, at room temperature for 15 minutes. Pharmacokinetic behavior of the agent was studied by carrying out biodistribution and scintigraphic imaging studies in normal Wistar rats. Clinical studies were performed by administering the preparation in patients suffering from disseminated skeletal metastases. RESULTS: Five batches of freeze-dried EDTMP kits with 50 kit vials in each batch were prepared. Each kit vial comprised a lyophilized mixture of 35 mg EDTMP, 14.1 mg NaOH, and 5.8 mg of CaCO3. The (177)Lu-EDTMP complex was prepared with excellent radiochemical purity (>99%) and high stability (>98% until 9 days postpreparation) using these kits. Radiochemical studies showed that this kit could be used within a pH range of 6-9 and with (177)Lu having specific activity as low as 925 GBq · g(-1) (25 Ci · g(-1)) for the preparation of up to 3.7 GBq (100 mCi) of (177)Lu-EDTMP. Biodistribution studies in animals revealed selective accumulation of the agent in skeleton (∼ 60% of the injected activity) with major renal clearance. Preliminary clinical studies in 10 patients exhibited selective accumulation of the radiotracer in skeletal lesions and provided significant pain relief thereby improving the quality of life of the patients. CONCLUSION: Freeze-dried EDTMP kits, suitable for the preparation of patient doses of (177)Lu-EDTMP, have been developed and used in preliminary studies for treating the cancer patients with disseminated skeletal metastases. The kit may also find use for the preparation of other potential bone pain palliation agents, such as (153)Sm-EDTMP.