First Preclinical Imaging of Primary Cartilage Neoplasm and Its Local Recurrence Using ^99mTc-NTP 15-5 Radiotracer

Abstract

This study on a rat model of grade II chondrosarcoma aimed to determine whether the radiotracer N-(triethylammonium)-3-propyl- [15]ane-N5 radiolabeled with 99m Tc ( 99m Tc-NTP 15-5), which binds to cartilage proteoglycans, has pathophysiologic validity for in vivo imaging of cartilage tumoral tissue. Methods: We used 2 experimental approaches with the Swarm chondrosarcoma rat model: that is, a primary paratibial location and local recurrence after intralesional curettage. 99m Tc-NTP 15-5 scintigraphy and 99m Tc-hydroxymethylenediphosphonate ( 99m Tc-HMDP) scanning were performed at regular intervals during 50 d after tumor implantation in a paratibial location (primary model; n 5 12 animals) and after intralesional curettage in a femoral condyle location (recurrence model; n 5 9 animals). For each animal, positive scans were analyzed at each time point using the targetto-background ratio (TBR), with the target region of interest delineated over the tumor and the background region of interest over muscle. In each model, the TBR time course was followed against primary tumoral growth or recurrence. Tumor volume was monitored for 2 mo by measuring the 2 perpendicular diameters. At study end, animals were sacrificed for histopathologic analysis. Results: For both models, 99m Tc-NTP 15-5 scans showed tracer accumulation at the site of implantation or curettage. For the primary tumor model, the mean TBR was 1.6 6 0.14 by day 4 after implantation and increased over time as the disease progressed, with a mean TBR of 4.25 6 0.25 on day 45. For the recurrence model, mean TBR was 3.27 6 0.24 by day 4 after curettage and increased with recurrence, with a mean value of 5.25 6 0.49 on day 50. 99m Tc-HMDP bone scans were negative for both models throughout the study; at a later stage of the study, an area of 99m Tc-HMDP accumulation was seen in the diaphysis of the bone adjacent to the tumor and was attributed to remodeling. Conclusion: These experimental results in 2 preclinical models of grade II chondrosarcoma bring forward data in favor of 99m Tc-NTP 15-5 radiotracer for imaging primary growth of chondrosarcoma and its local recurrence after surgery.

99mTc-NTP 15-5 Imaging for Cartilage Involvement in Experimental Rheumatoid Arthritis: Comparison with Routinely Used Molecular Imaging Methods and Sensitivity to Chronic Nonsteroidal Antiinflammatory Drug Treatment

“…99m Tc-NTP 15-5 was previously demonstrated to be a candidate for the in vivo functional monitoring of proteoglycan remodeling associated with degenerative and tumoral pathologies of cartilage (15)(16)(17)(18)24). We evaluated, in an RA model, the relevance of 99m Tc-NTP 15-5 imaging for monitoring in vivo cartilage damage and response to nonsteroidal antiinflammatory drug therapy.…”

Imaging technologies for preclinical models of bone and joint disorders

“…joints (knees, shoulders), spine and skull (Figure 5). SPECT imaging of articular cartilage in rodents has been reported using N -[triethylamonium]-3-propyl-[15]ane-N (NTP) bound to Tc-99 m. NTP has a high affinity for binding to negatively charged sulphate groups of the glycosaminoglycans, a major component of the cartilage matrix, and it has been successfully used for in vivo imaging of a cartilage tumoural model in rats [48]. …”

Quaternary ammonium-melphalan conjugate for anticancer therapy of chondrosarcoma: in vitro and in vivo preclinical studies

“…Since experiments with the SRC model have Interestingly, the treatment protocol proved well tolerated, since the animals showed no weight loss over the course of the study. Antitumour effect was also assessed in vivo by 99m Tc-NTP 15-5 scintigraphic imaging, which was previously demonstrated in the SRC orthotopic model to provide suitable criteria for monitoring cartilage tumour [20].…”

“…The 99m Tc-N-[triethylammonium]-3-propyl-15ane-N5 ( 99m Tc-NTP 15-5) radiotracer was prepared and radiolabelled as previously published (specific radioactivity of 25 MBq/μmol), and administered by i.v. route to anaesthetized animals (40 MBq/animal) [20]. The animals were anaesthetized intraperitoneally with a mixture of ketamine (50 mg/kg) (Imalgène 500, Merial, France) and xylazine (10 mg/kg) (Rompun 2%, Bayer, France).…”