Towards a Radio-guided Surgery with β−\beta^{-} Decays: Uptake of a somatostatin analogue (DOTATOC) in Meningioma and High Grade Glioma

A novel radio guided surgery (RGS) technique for cerebral tumors using $\beta^{-}$ radiation is being developed. Checking the availability of a radio-tracer that can deliver a $\beta^{-}$ emitter to the tumor is a fundamental step in the deployment of such technique. This paper reports a study of the uptake of 90Y labeled (DOTATOC) in the meningioma and the high grade glioma (HGG) and a feasibility study of the RGS technique in these cases.Comment: 21 pages, 5 figure

Investigation of 90Y-avidin for prostate cancer brachytherapy: A dosimetric model for a phase I-II clinical study

Purpose: A novel method for prostate irradiation is investigated. Similarly to 125I or 103Pd seed brachytherapy, 90Y- avidin could be injected via the perineum under ultrasound image guidance. This study inspects the theoretical feasibility with a dosimetric model based on Monte Carlo simulation. Methods: A geometrical model of the prostate, urethra and rectum was designed. The linear-quadratic model was applied to convert 125I absorbed dose prescription/constraints into 90Y dose through biological effective dose (BED) calculation. The optimal 90Y-avidin injection strategy for the present model was obtained. Dose distribution was calculated by Monte Carlo simulation (PENELOPE,GEANT4). Dose volume histograms (DVH) for the prostate, urethra and rectum were compared to typical DVHs of 125I seed brachytherapy, used routinely in our institute. Results: With 90Y-avidin, at least 95 % of the prostate must receive more than 70 Gy. The absorbed dose to 10 % of the urethra (D 10%-urethra) and the maximum absorbed dose to the rectum (D max-rectum) must be lower than 122 Gy. For the present model, the optimum strategy consists in multiple injections of 90Y-avidin 50 μl drops, for a total volume of 3.1 ml. The minimum activity to deliver the prescribed absorbed dose is 0.7 GBq, which also fully respects urethral and rectal constraints. The resulting dose map has a maximum in the central region with a sharp decrease towards the urethra and the prostate edge. Notably, D 10%-urethra is 95 Gy and Dmax-rectum is below 2 Gy. Prostate absorbed dose is higher with 90Y-avidin than 125I seeds, although the total volume receiving the prescribed absorbed dose is 1-2 % lower. Urethral DVH strictly depends on the 90Y distribution, to be optimized according to prostate shape; in our model, BED30%-urethra is 90 Gy with 90Y-avidin, whereas for patients receiving 125I seeds it ranges between 150 and 230 Gy. The rectal DVH is always more favourable with 90Y. Conclusion: The methodology is theoretically feasible and can deliver an effective treatment in T1-T2 prostate cancer. Pharmacokinetic and biodistribution studies in prostate cancer patients are needed for validation. © 2013 Springer-Verlag Berlin Heidelberg

Sentinel node detection by lymphoscintigraphy and sentinel lymph node biopsy in vulvar melanoma

Purpose: Vulvar melanoma is a rare malignant tumour. Its surgical excision is the mainstay of treatment whilst the surgical management of regional lymph nodes remains controversial; on the contrary elective inguinofemoral lymphadenectomy causes considerable morbidity. Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) are accurate staging procedures of lymph node status in breast cancer and cutaneous melanoma patients. In this retrospective paper we report our experience of LS and SLNB in vulvar melanoma patients. Methods: Twenty-two consecutive patients with a diagnosis of vulvar melanoma were treated at our institute: patients with clinically positive groin nodes or with previous surgery on the primary tumour were excluded. Twelve were selected for our analysis. All patients underwent sentinel lymph node localization with LS the day before surgery and the surgical procedure of SLNB associated with radical surgery. Results: Six patients had metastatic SLNB and in five of six (83.3%) it was the only positive node. In the other six patients SLNB was negative for metastatic disease. No skip metastases were observed. In SLNB negative patients the mean Breslow thickness was 2.06 mm (range: 0.60-7.10) and only one patient showed a high Breslow thickness (patient 8). In SLNB positive patients the mean Breslow thickness was 4.33 mm (1.8-6.0). Conclusion: Our data indicate that, even in vulvar melanoma, the sentinel lymph node pathological status predicts the pathological status of the remaining groin nodes and suggests that elective groin dissection can be spared in cases of a negative SLNB. Breslow thickness (<1 mm) was not predictive of negative nodes. © 2010 Springer-Verlag

3D dosimetry in patients with early breast cancer undergoing Intraoperative Avidination for Radionuclide Therapy (IART®) combined with external beam radiation therapy

Purpose Intraoperative Avidination for Radionuclide Therapy (IART®) is a novel targeted radionuclide therapy recently used in patients with early breast cancer. It is a radionuclide approach with 90Y-biotin combined with external beam radiotherapy (EBRT) to release a boost of radiation in the tumour bed. Two previous clinical trials using dosimetry based on the calculation of mean absorbed dose values with the hypothesis of uniform activity distribution (MIRD 16 method) assessed the feasibility and safety of IART®. In the present retrospective study, a voxel dosimetry analysis was performed to investigate heterogeneity in distribution of the absorbed dose. The aim of this work was to compare dosimetric and radiobiological evaluations derived from average absorbed dose vs. voxel absorbed dose approaches. Methods We evaluated 14 patients who were injected with avidin into the tumour bed after conservative surgery and 1 day later received an intravenous injection of 3.7 GBq of 90Y-biotin (together with 185 MBq 111In-biotin for imaging). Sequential images were used to estimate the absorbed dose in the target region according to the standard dosimetry method (SDM) and the voxel dosimetry method (VDM). The biologically effective dose (BED) distribution was also evaluated. Dose/volume and BED volume histograms were generated to derive equivalent uniform BED (EUBED) and equivalent uniform dose (EUD) values. Results No "cold spots" were highlighted by voxel dosimetry. The median absorbed-dose in the target region was 20 Gy (range 15-27 Gy) by SDM, and the median EUD was 20.4 Gy (range 16.5-29.4 Gy) by the VDM; SDM and VDM estimates differed by about 6 %. The EUD/mean voxel absorbed dose ratio was >0.9 in all patients, indicative of acceptable uniformity in the target. The median BED and EUBED values were 21.8 Gy (range 15.9-29.3 Gy) and 22.8 Gy (range 17.3-31.8 Gy), respectively. Conclusion VDM highlighted the absence of significant heterogeneity in absorbed dose in the target. The EUD/ mean absorbed dose ratio indicated a biological efficacy comparable to that of uniform distribution of absorbed dose. The VDM is recommended for improving accuracy, taking into account actual activity distribution in the target region. The radiobiological model applied allowed us to compare the effects of IART® with those of EBRT and to match the two irradiation modalities. © Springer-Verlag 2012

Peptide receptor radionuclide therapy with 177Lu-DOTATATE: The IEO phase I-II study

Purpose: Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst 2), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of 177Lu-DOTATATE in multiple cycles. Methods: Fifty-one consecutive patients with unresectable/metastatic sst 2-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of 177Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. Results: No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Nonresponders and patients with extensive tumour involvement had lower survival. Conclusion: 177Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. © Springer-Verlag 2011

Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: Results of a phase II study with 90Y-labeled biotin

Purpose: External beam radiotherapy (EBRT) after conservative surgery for early breast cancer requires 5-7 weeks. For elderly patients and those distant from an RT center, attending for EBRT may be difficult or impossible. We investigated local toxicity, cosmetic outcomes, and quality of life in a new breast irradiation technique-intraoperative avidination for radionuclide therapy (IART)-in which avidin is administered to the tumor bed and 90Y-labelled biotin later administered intravenously to bind the avidin and provide irradiation. Reduced duration EBRT (40 Gy) is given subsequently. Methods: After surgery, 50 (ten patients), 100 (15 patients) or 150 mg (ten patients) of avidin was injected into the tumor bed. After 12-24 h, 3.7 GBq 90Y-biotin (beta source for therapeutic effect) plus 185 MBq 111In-biotin (gamma source for imaging and dosimetry) was infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to 30 h. Shortened EBRT started 4 weeks later. Local toxicity was assessed by RTOG scale; quality of life was assessed by EORTC QOL-30. Results: Of 35 patients recruited (mean age 63 years; range 42-74) 32 received IART plus EBRT. 100 mg avidin provided 19.5±4.0 Gy to the tumor bed and was considered the optimum dose. No side-effects of avidin or 90Y-biotin occurred, with no hematological or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART plus EBRT was well accepted, with good cosmetic outcomes and maintained quality of life. Conclusions: IART plus reduced EBRT can accelerate irradiation after conservative breast surgery. © 2009 Springer-Verlag