Preparation, Quality Control and Biodistribution Studies of two [111In]-Rituximab Immunoconjugates

Abstract

In order to use Auger-electron therapeutic effects in CD20 antigen targeting in lymphomas, Mabthera™ (rituximab) N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA-NHS) and ccDTPA separately. Conjugated-Rituximab was obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH=7.8) to a glass tube pre-coated with freshly prepared DOTA-NHS or ccDTPA (0.01-0.1 mg) at 25°C. Radiolabeling was performed at 37°C in 3hand room temperature for one hour for DOTA-conjugate and DTPA-conjugate respectively. HPLC showed an overall radiochemical purity of 97.5 and 95% for DOTA and DTPA-conjugates respectively (Specific activity =2800-5600 GBq/mM). The final isotonic 111In-rituximab complexes were checked by gel electrophoresis for radiolysis. Preliminary biodistribution studies in normal rat model performed to determine radioimmunoconjugates distribution of up to 48h.

Estimated human absorbed dose for 68Ga-ECC based on mice data: comparison with 67Ga-ECC

“…The HPGe detector gives us count; therefore, we had used the below formula to convert the counts into the activity [30]:…”

Assessment of the effective absorbed dose of 4-benzyl-1-(3-[125I]-iodobenzylsulfonyl)piperidine in humans on the basis of biodistribution data of rats

“…On the basis of the promising results of the biodistribution data of 4-benzyl-1-(3-[ 125 I]-iodobenzylsulfonyl)piperidine (4-B-[ 125 I]-IBSP) obtained from normal rats, it was concluded that this tracer may be used as an imaging agent for early detection of various cancers such as breast, prostate, liver, and lung cancers, although internal dosimetry calculations are still needed. Pursuant to our previous studies on the estimation of human absorbed doses based on biodistribution data obtained from rodents [18][19][20][21][22], in the current study, the authors endeavored to perform a robust description of organ biodistribution because of a large amount of biodistribution data (source organs in dosimetry calculations). Efforts were taken to estimate the effective radiation dose absorbed by human organs following intravascular administration of 4-B-[ 125 I]-IBSP by using biodistribution data from normal rats.…”

Comparison of estimated human effective dose of 67Ga- and 99mTc-labeled bombesin based on distribution data in mice

“…Organs (blood, heart, liver, right kidney, left kidney, muscle, trabecular bone, intestine, pancreas, lung, stomach, tail, spleen and adrenal) were removed, washed with normal saline and dried in paper toweling. Each sample was weighed and counted with an HPGe detector 3 times, together with standards prepared from a sample of the injected material [26]. In order to minimize the uncertainties' all the samples counts were higher than 10,000, which results SD of less than 1 %.…”