Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

Abstract

Abstract.To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177 Lu-octreotate and 111 In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177 Lu-octreotate or 111 In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111 In-MG0. Animals were sacrificed 1-7 days after injection in the 177 Lu-octreotate study and 1 h after injection of 111 In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177 Lu were calculated. There was a specific tumor uptake of either 177 Lu-octreotate or 111 In-MG0. 177 Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177 Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.

Radionuclide Therapy via SSTR: Future Aspects from Experimental Animal Studies

“…In the GOT1 model, all T/NT studied increased with time 3–14 days after injection of 177 Lu-octreotide [81]. Similar results were found in the GOT2 model [36]. …”

“…In the GOT1 model, saturation was found at peptide amounts >1 µg of 111 In-DTPA-octreotide [84]. In the GOT2 model, with much lower SSTR expression, saturation occurred in both tumour tissue and SSTR-expressing pancreas/adrenals for 177 Lu-octreotate at lower peptide levels [36]. To avoid SSTR saturation, low peptide amounts should be used which necessitates high specific activity of the radiolabelled peptide, prolonged infusion time, or fractionated administration of the radiopharmaceutical.…”

“…expression of SSTR [34]. The human medullary thyroid carcinoma (MTC) cell line GOT2 has a slow growth rate and much lower SSTR expression than GOT1 [35,36]. TT is another SSTR-expressing MTC cell line [37].…”

Distinct microRNA Expression Profiles in Mouse Renal Cortical Tissue after 177Lu-octreotate Administration

“…The cumulated activity was estimated from the measured activity concentration together with data from a previously published biodistribution study of 177 Lu-octreotate in BALB/c nude mice [27].…”

Diabody Pretargeting with Click Chemistry In Vivo

“…However, on glomerular filtration, peptides and antibody fragments are generally reabsorbed by the proximal tubule cells in the kidneys to prevent the loss of valuable amino acids, and this step is followed by lysosomal degradation (3). With regard to radiometal-labeled agents, the catabolic radiometal products have been shown to have prolonged renal entrapment, which typically hampers nuclear imaging and radioimmunotherapy procedures with these agents because of possible nephrotoxicity (4)(5)(6)(7)(8)(9)(10). Therefore, strategies that reduce the renal uptake of radiometallabeled low-molecular-weight agents to enable the administration of higher radiation doses with reduced risk for nephrotoxicity remain of great interest.…”