Doubling time (DT) is widely used for quantification of tumor growth rate. DT is usually determined from two volume estimations with measurement time intervals comparable with or shorter than DT. Clinical data show that the frequency distribution of DT in patients is positively skewed, with some very long DT values compared with the average DT. Growth rate can also be quantified using specific growth rate (SGR; %/d), equal to ln2/DT. The aim of this work was to compare DT and SGR as growth rate variables. Growth rate calculations were computer simulated for a tumor with DT of 100 days, measurement time interval of 1 to 200 days, and volume estimation uncertainty of 5% to 20%. Growth rate variables were determined and compared for previously published clinical data. The study showed that DT is not a suitable variable for tumor growth rate because (a) for short measurement time intervals, or high volume uncertainties, mean DT can either overestimate or underestimate the average growth rate; (b) DT is not defined if the consecutively estimated volumes are equal; and (c) the asymmetrical frequency distribution of DT makes it unsuitable for common statistical testing. In contrast, mean SGR and its equivalent DT give the correct values for average growth rate, SGR is defined for all tumor volume changes, and it has a symmetrical frequency distribution. SGR is also more accurate to use when discussing, for example, growth fraction, cell loss rate, and growth rate heterogeneities within the tumor. SGR should thus be used, instead of DT, to quantify tumor growth rate. [Cancer Res 2007;67(8):3970-5]

Tc/EDDA)NH 2 ]-exendin-4 did not result in inferior tumor-to-organ ratios or reduced image quality. All radiopeptides tested showed a high tumor-to-background ratio, resulting in the visualization of small tumors (maximum diameter between 1.0 and 3.2 mm) by SPECT and PET. The only exception was the kidneys, which also showed high uptake. This uptake could be reduced by 49%278% using poly-glutamic acid, Gelofusine, or a combination of the 2. The estimated effective radiation dose was 3.7 mSv/MBq for [Lys 40

In recent years, 47 Sc has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 keV; Eγ, 159 keV) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of 47 Sc for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used. Methods: 47 Sc was produced via the 46 Ca(n,γ) 47 Ca! b − 47 Sc nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the 47 Sc from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. 47 Sc-labeled cm10 was tested on folate receptor-positive KB tumor cells in vitro. Biodistribution and SPECT imaging experiments were performed in KB tumor-bearing mice. Radionuclide therapy was conducted with two groups of mice, which received either 47 Sc-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice. Results: Irradiation of 46 Ca resulted in approximately 1.8 GBq of 47 Ca, which subsequently decayed to 47 Sc. Separation of 47 Sc from 47 Ca was obtained with 80% yield in only 10 min. The 47 Sc was then available in a small volume (∼500 μL) of an ammonium acetate/HCl (pH 4.5) solution suitable for direct radiolabeling. 47 Sc-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro 47 Sccm10 showed folate receptor-specific binding and uptake into KB tumor cells. In vivo SPECT/CT images allowed the visualization of accumulated radioactivity in KB tumors and in the kidneys. The therapy study showed a significantly delayed tumor growth in mice, which received 47 Sc-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice. Conclusion: With this study, we demonstrated the suitability of using 47 Sc for therapeutic purposes. On the basis of our recent results obtained with 44 Sc-folate, the present work confirms the applicability of 44 Sc/ 47 Sc as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.

PurposeTo present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED).MethodTreatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 ± 2 Gy (α/β = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 ± 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR).ResultsFifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function.ConclusionsIndividualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3678-4) contains supplementary material, which is available to authorized users.