Intratumoral Administration of Holmium-166 Acetylacetonate Microspheres: Antitumor Efficacy and Feasibility of Multimodality Imaging in Renal Cancer

Abstract

PurposeThe increasing incidence of small renal tumors in an aging population with comorbidities has stimulated the development of minimally invasive treatments. This study aimed to assess the efficacy and demonstrate feasibility of multimodality imaging of intratumoral administration of holmium-166 microspheres (166HoAcAcMS). This new technique locally ablates renal tumors through high-energy beta particles, while the gamma rays allow for nuclear imaging and the paramagnetism of holmium allows for MRI.Methods 166HoAcAcMS were administered intratumorally in orthotopic renal tumors (Balb/C mice). Post administration CT, SPECT and MRI was performed. At several time points (2 h, 1, 2, 3, 7 and 14 days) after MS administration, tumors were measured and histologically analyzed. Holmium accumulation in organs was measured using inductively coupled plasma mass spectrometry.Results 166HoAcAcMS were successfully administered to tumor bearing mice. A striking near-complete tumor-control was observed in 166HoAcAcMS treated mice (0.10±0.01 cm3 vs. 4.15±0.3 cm3 for control tumors). Focal necrosis and inflammation was present from 24 h following treatment. Renal parenchyma outside the radiated region showed no histological alterations. Post administration CT, MRI and SPECT imaging revealed clear deposits of 166HoAcAcMS in the kidney.ConclusionsIntratumorally administered 166HoAcAcMS has great potential as a new local treatment of renal tumors for surgically unfit patients. In addition to strong cancer control, it provides powerful multimodality imaging opportunities.

Intratumoral injection of radioactive holmium (166Ho) microspheres for treatment of oral squamous cell carcinoma in cats

“…As a result, the “treatment volume” was determined to be 1.5 × the tumour volume as measured on CT images. In addition, extra activity was ordered to account for anticipated losses of 166 Ho MS during suspension and syringe preparation, and during the administration procedure (residual 166 Ho MS remaining in the syringes after intratumoral injections and possible spillage outside of the tumour) …”

“…Initially, the treatment was started in a pilot setting ( n = 5) using a relatively high 166 Ho activity, aiming for a tumour‐absorbed dose of 400 to 800 Gy. This relatively high‐tumour dose was chosen to overcome possible focal low‐absorbed dose areas in the tumour because of inhomogeneous 166 Ho MS distribution and peritumoral deposition of 166 Ho MS. Based on previous pilot experiments, a “loss” of >50% of 166 Ho MS was expected during treatment due to possible leakage of 166 Ho MS out of the tumour needle tracts and premature settling and accumulation of 166 Ho MS in the syringe and needle dead space. A substantial additional loss of 166 Ho MS was anticipated during the process of microsphere suspension and preparation of the syringes for treatment.…”

“…In these studies, it was shown that extremely high tumour‐absorbed doses could be attained (in excess of 6 times the absorbed dose that can be achieved with external beam radiotherapy) without major associated side effects . 166 Ho microbrachytherapy can therefore potentially be a safe and effective treatment option for both human and veterinary patients with head and neck cancer for whom no other treatment options are available . The objective of this study was to prospectively evaluate safety and efficacy of 166 Ho microbrachytherapy in cats with spontaneous unresectable FOSCC.…”

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres

“…All energy was assumed to be absorbed in the extrahepatic deposition location, because the mean penetration of the b emission of 166 Ho (2.5 mm) is small, compared with the measured volumes (15).…”

Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

“…Meanwhile, a number of compounds labeled with therapy radionuclides have been employed for cancer treatment through intratumoral administration [12][13][14][15] . Compared with traditional high-dose external radiation, intratumoral administration delivers more radioactivity to the tumor than the normal structure [16] .…”