Novel bioerodable eluting-spacers for radiotherapy applications with in situ dose painting

Objective: To investigate feasibility of using bioerodable/bioerodible spacers (BES) over biodegradable spacers (BDS) loaded with gold nanoparticles for radiotherapy applications with in situ dose-painting, and to explore dosimetric impact on dose enhancement ratio of different radioisotopes. Methods: Analytical models proposed were based on experimentally reported erosion rate constant (k 0 = 5. 5E-7 kgm− 2s− 1 ) for bioerodible polymeric matrix. An in vivo determined diffusion coefficient (2.2E-8 cm2/s) of 10 nm gold nanoparticles (AuNP) of concentration 7 mg/g was used to estimate diffusion coefficient of other AuNP sizes (2, 5, 14 nm) using the Stoke–Einstein diffusion equation. The corresponding dose enhancement factors (DEF) were used to study dosimetric feasibility of employing AuNP-eluting BPS for radiotherapy applications. Results: The results showed AuNP release period from BES was significantly shorter (116 h) compared to BDS (more than a month) reported previously. The results also agree with reported Hopfenberg equation for a cylindrical matrix undergoing surface erosion. The DEF at tumour distance 5 mm for Cs-131 (DEF > 2.2) greater than that of I-125 (DEF > 2) and Pd-103 (DEF ≥ 2) could be achieved for AuNP sizes (2, 5, 10, and 14 nm) respectively. Conclusion: Our findings suggested that BES could be used for short-lived radioisotopes like Pd-103 and Cs-131 in comparison to eluting BDS which is feasible for long-lived radioisotopes like I-125. Advances in knowledge: The study provides scientific basis for development of new generation eluting spacers viable for enhancing localized tumour dose. It concludes that BES gives higher DEF for Cs-131, and good candidate for replacing conventional fiducials/spacers.

Twins in spirit part IV – [177Lu] high affinity DOTATATE

Summary Aim: Besides the use of somatostatin analogues, small molecules like sunitinib and everolimus as well as conventional chemotherapy, peptide receptor radiotherapy (PRRT) using radiolabelled somatostatin analogues has gained an important role in the treatment of inoperable, metastasized neuroendocrine tumours (NET). There are various radiotracers in use. Based on our experience with the PET tracer [68Ga]DOTA-3-iodo- Tyr3-octreotate ([68Ga]HA-DOTATATE), a DOTATATE derivative with an increased binding affinity to hsst5, the current retrospective analysis is exploring the therapeutic potential of [177Lu]HA-DOTATATE. Methods: Eighteen patients with metastatic NET (G1/G2) were treated using [177Lu]DOTATATE and/or [177Lu]HA-DOTATATE, and dosimetric results of both tracers were compared. Results: Using [177Lu]HA-DOTATATE, a mean tumour dose of 5.34 Gy/GBq (median 2.53 Gy/ GBq; range 0.89-33.3 Gy/GBq) was achieved, while [177Lu]DOTATATE delivered a tumour dose of 5.53 Gy/GBq (median 2.70 Gy/GBq; range 0.44-15.3 Gy/GBq). Organ doses for [177Lu]HA-DOTATATE vs. [177Lu]DOTATATE were as follows: kidney 2.31 ± 0.85 vs. 2.03 ± 0.96 Gy/GBq, liver 1.6 ± 0.79 vs. 1.67 ± 1.73 Gy/GBq, spleen 3.89 ± 4.04 vs. 4.50 ± 3.69 Gy/GBq and whole body 0.16 ± 0.10 Gy/GBq vs. 0.15 ± 0.08 Gy/ GBq. Tumour-to-kidney dose ratio was slightly higher for [177Lu]DOTATATE (2.4 ± 5.6) compared to [177Lu]HA-DOTATATE (1.5 ± 3.6). Conclusion: Both tracers showed marked inter-patient variation in their dosimetry, and no significant differences in dosimetry of [177Lu]HA- DOTATATE and [177Lu]DOTATATE were observed when taking all patients into account. Thus, [177Lu]HA-DOTATATE appears viable for PRRT, although it was marginally inferior regarding kidney dose and tumour-to-kidney dose ratio compared to the established [177Lu]DOTATATE.