• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.84-93
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• 1999

Purpose: We investigated the direct labeling method of antibody with $^{99m}Tc$ and $^{188}Re$ and examined the stability and function of these labeled compounds in in vitro and in vivo. Materials and Methods: Disulfide bond of nonspecific human IgG was reduced to -SH group by 2-mercaptoethanol. Stannous ion was used to reduce $^{99m}Tc$ and $^{188}Re$. The stability of $^{99m}Tc$-IgG and $^{188}Re$-IgG was estimated upto 24 hrs. Biodistribution was evaluated in abscess bearing rats at 4 and 24 hr post-injection of $^{99m}Tc$ or $^{188}Re$ labeled IgG. Results: The number of -SH group per reduced IgG molecule was 2.34. The labeling yield of $^{99m}Tc$-IgG and $^{188}Re$-IgG were 90% and 95%, respectively The stability of $^{99m}Tc$-IgG at 1, 4, 6 and 24 hr was 91%, 83%, 78%, 7% and that of $^{188}Re$-IgG at 1, 4, 16 and 24 hr was 94%, 80%, 47%, 42%, respectively. At 4 hr post-injection of $^{99m}Tc$-IgG, high uptake was found on kidney, blood, stomach and abscess ($9.42{\pm}0.68,\;1.43{\pm}0.24,\;0.86{\pm}0.18,\;0.72{\pm}0.10$ %ID/g, respectively). The uptakes at 24 hr were kidney, abscess,.itomach, and blood in descending order. In case of $^{188}Re$-lgG, high uptake at 4 hr post injection appeared on kidney, blood, abscess and stomach ($3.92{\pm}0.62,\;1.32{\pm}0.08,\;0.88{\pm}0.01,\;0.26{\pm}0.06$, respectively). The uptakes at 24 hr were kidney, abscess, blood and stomach in descending order. The abscess to blood uptake ratio of $^{99m}Tc$-IgG was 0.5 at 4 hr and 2.02 at 24 hr and that of $^{188}Re$-IgG was 0.67 and 1.29. Conclusion: $^{99m}Tc$-IgG and $^{188}Re$-IgG canbe labeled efficiently with direct labeling method. However, $^{99m}Tc$-IgG and $^{188}Re$-IgG, labeled with direct method, was unstable. Further study is needed to enhance the stability of the antibody labeling.

• Proceedings of the Korean Nuclear Society Conference
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• 2001.05a
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• pp.433-433
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• 2001

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.26-35
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• 2019

$^{188}Re$ is one of the most readily available generator derived and useful radionuclides for therapy emitting ${\beta}^-$ particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The $^{188}W/^{188}Re$ generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (NCA) $^{188}Re$ suitable for the preparation of radiopharmaceuticals for radionuclide therapy. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on $^{188}Re$ -labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. In this review, we addressed the current development status of $^{188}Re$ radiopharmaceuticals for liver cancer therapy and their applications.

• The Korean Journal of Nuclear Medicine
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• v.36 no.3
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• pp.195-202
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• 2002

Purpose: For clinical application of beta-emitter labeled antibody, high specific activity is imporiant. Carrier-free $^{188}Re$ from $^{188}W/^{188}Re$ generator is an ideal radionuclide for this purpose. However, low stability of $^{188}Re$ labeled antibody, especially in high specific activity, due to radiolytic decomposition by high energy (2.1 MeV) beta ray was problem. We studied the stability of $^{188}Re$ labeled antibody, and stabilizing effect of several stabilizers. Materials and Methods: Pre-reduced monoclonal antibody (CEA79.4) was labeled with $^{188}Re$ by incubating with generator-eluted $^{188}Re-perrhenate$ in the presence of stannous tartrate for 2 hr at room temperature. Radiochemical purity of each preparation was determined by chromatography. Human serum albumin was added to the labeled antibodies (2%). Stability of $^{188}Re-CEA79.4$ was investigated in the presence of ascorbic acid, ethanol, of Tween 80 as stabilizing agents. Results: Labeling efficiencies were $88{\pm}4%\;(n=12)$. Specific activities of $1.25{\sim}4.77MBq/{\mu}g$ were obtained. If stored after purging with $N_2$, all the preparations were stable for 10 hr. However, stability decreased in the presence of air. Perrhenate and $^{188}Re-tartrate$ was major impurity in declined preparation. colloid-formation was not a significant problem in all cases. Addition of ascorbic acid stabilized the labeled antibodies either under $N_2$ or under air by reducing the formation of perrhenate. Conclusion: High specific activity $^{188}Re$ labeled antibody is unstable, especially, in the presence of oxygen. Addition of ascorbic acid increased the stability.

• The Korean Journal of Nuclear Medicine
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• v.34 no.4
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• pp.344-352
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• 2000

Purpose: Re-188-Hydroxyethylidene diphosphonate (HEDP) is a new cost-effective agent for systemic radioisotope therapy of metastatic bone pain. We investigated the influence of carrier for labeling and biodistribution of Re-188-HEDP using HEDP kit with or without carrier ($KReO_4$). Materials and Methods: The kits (HEDP 15 mg, gentisic acid 4 mg and $SnCl_2.2H_2O_2$ 4.5 mg) with or without carrier ($KReO_4$ 0.1 mg) were labeled with Re-188 solution, made available from an in-house generator by boiling for 15 min. We compared the labeling efficiency and stability of carrier-added and carrier-free preparations of Re-188-HEDP Biodistribution and imaging studies of each preparation were performed in ICR mice ($1.85{\sim}3.7MBq/0.1ml$) and SD rats ($74.1{\sim}85.2MBq/0.5ml$). Results: The carrier-added preparation showed high labeling efficiency (95% at pH 5) and high stability in serum (88%, 3 hr). However, the carrier-free preparation showed low labeling efficiency (59% at pH 5) and low stability (43%, 3 hr). The carrier-added preparation showed high uptake in bone and low uptake in stomach and kidneys. However, the carrier-free preparation showed lower uptake in bone and higher uptake in both stomach and kidneys, which is supposed to be due to released perrhenate. The carrier-added preparation also showed better images with higher skeletal accumulation, lower uptake in other organs and lower soft tissue uptake than the carrier-free preparation. Conclusion: The results of these studies clearly demonstrate that addition of carrier perrhenate is required for high labeling efficiency, stability, bone uptake and good image quality of Re-188-HEDP.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.516-524
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• 1998

Purpose: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotherapy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. Materials and Methods: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH residue, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. Results: Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were $92.4{\pm}5.9%$ and $84.7{\pm}4.6%$, respectively, In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and $6.59{\times}10^9\;M^{-1}$, respectively, while those of Re-188-CEA79.4 were 41.6% and $4.2{\times}10^9\;M^{-1}$, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. Conclusion: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotheraphy.

• The Korean Journal of Nuclear Medicine
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• v.35 no.5
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• pp.293-300
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• 2001

The search for an ideal radioisotope for radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays with a short physical half-life of 16.9 hr, $^{188}Re$ is an excellent candidate for radiotherapy. Its applications Include the irradiation of coronary artery to prevent restenosis, treatment of rheumatoid arthritis, treatment of peritoneal effusion, palliation of metastatic bone pain, and treatment of liver cancer.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.168-172
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• 2003

Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.81-88
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• 1998

The purpose of this study was to examine the radiolabeling and biodistribution of $^{188}Re(V)$-DMSA as a therapeutic cancer radiopharmaceutical. We made a DMSA kit($NaHCO_3$ 1.5 mg, meso-2,3-dimercaptosuccinic acid 1.0 mg, L(+)-ascorbic acid 0.7 mg, $SnCl_2{\cdot}2H_2O$ 0.34 mg, pH 2.9) for labeling with $^{188}Re$. In this kit, $^{188}ReO_4{^-}$ 5 mCi/2 ml added and boiled at $100^{\circ}C$ for 3 hr in water bath. The final pH adjusted to 7.5 with 7% $NaHCO_3$ solution. We checked the labelling efficacy with TLC-SG(n-butanol : acetic acid : $H_2O$ = 3 : 2 : 3) and examined the stability both in room temperature and in serum at $37^{\circ}C$. Biodistribution(1, 3, 13, 24, 48 hr) of $^{188}Re(V)$-DMSA compound was evaluated in Sarcoma 180 tumor-bearing mice. Each labeling efficiency and stability at room temperature for 48 hours was over 98% and 95%, respectively. The stability in serum were 82%(6 hr) and 85%(48 hr). Tumor uptake of $^{188}Re(V)$-DMSA in Sarcoma 180-bearing mice were $0.66{\pm}0.15%$(1 hr), $0.51{\pm}0.10%$(3 hr), $0.19{\pm}0.05%$(24 hr) and $0.13{\pm}0.02%$(48 hr). These result are consistent with those of $^{99m}Tc(V)$-DMSA which were reported previously. In conclusion, $^{188}Re(V)$-DMSA may be a useful therapeutic radiopharmaceutical for treating some cancers and metastatic bone lesion.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.3-10
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• 2019

The activities per volume of $^{188}Re$ and $^{99m}Tc$ from their generators are dependent on the specific activity of their mother nuclides $^{188}W$ and $^{99}Mo$ respectively. After a particular lapse of time, the eluted RI activity is exponentially reduced and thus cannot satisfy the needs of clinical application. The purpose of this study is to develop a $^{188}Re$ and $^{99m}Tc$ concentration device with a compact size that can extend the period of use as well as conveniently concentrate the RI. We designed the concentration module by including two-different check valves that do not required any manual on-off operations. In these concentration process, cation exchange resin embedded with Ag and anion exchange resins were used. After completing the concentrating step, the recovering yield was identified to be more than 93% for $^{188}Re$ generators and 88% for $^{99m}Tc$ generators. Moreover, all these procedures were done within 5 min.