Monitoring renal function during chemotherapy.

PURPOSE: Renal function is monitored during chemotherapy because chemotherapeutic drugs are excreted by the kidneys and are potentially nephrotoxic. Doses are adjusted according to the glomerular filtration rate (GFR), i.e. the more reduced the GFR, the lower the treatment dose. Plasma clearance of (51)Cr-EDTA is a reliable indicator of GFR before and during treatment with potentially nephrotoxic drugs, but its measurement is costly. GFR can also be estimated using an algorithm that converts plasma creatinine concentration to GFR, e.g. the MDRD equation. The aim of this investigation was to evaluate the reliability of estimated GFR (eGFR) in detecting changes in GFR as assessed by the MDRD equation in cancer patients treated with nephrotoxic chemotherapeutic drugs. METHODS: We included all patients from the Department of Oncology undergoing chemotherapy who were referred to the Department of Nuclear Medicine for measurement of GFR by the (51)Cr-EDTA plasma clearance technique at least four times during the study period of 12 months. The eGFR was calculated from plasma creatinine concentration and the MDRD formula. GFR was determined by the (51)Cr-EDTA plasma clearance method. RESULTS: In 48 patients with a mean age of 47 years, GFR decreased from 86 to 73 ml/min/1.73 m(2) (mean values, p < 0.002) from the first to the last measurement, whereas plasma creatinine concentration and eGFR remained unchanged. In 13 patients (27 %) the finding of a decreased GFR led to adjustment of the dose of the chemotherapy drug. Eight of the 13 patients with decreased GFR also had a reduced eGFR but five patients had a normal eGFR. These five patients would have been treated with the nephrotoxic drug at a dose that was too high. CONCLUSION: Neither creatinine plasma concentration nor eGFR (MDRD) can be recommended as a replacement for measurement of GFR with the (51)Cr-EDTA plasma clearance method in patients treated with nephrotoxic cytostatic drugs.

Edelman's equation is valid in acute hyponatremia in a porcine model: plasma sodium concentration is determined by external balances of water and cations.

Acute hyponatremia is a serious condition, which poses major challenges. Of particular importance is what determines plasma sodium concentration ([Na(+)]). Edelman introduced an explicit model to describe plasma [Na(+)] in a population as [Na(+)] = alpha.(exchangeable Na(+) + exchangeable K(+))/(total body water) - beta. Evidence for the clinical utility of the model in the individual and in acute hyponatremia is sparse. We, therefore, investigated how the measured plasma [Na(+)] could be predicted in a porcine model of hyponatremia. Plasma [Na(+)] was estimated from in vivo-determined balances of water, Na(+), and K(+), according to Edelman's equation. Acute hyponatremia was induced with desmopressin acetate and infusion of a 2.5% glucose solution in anesthetized pigs. During 480 min, plasma [Na(+)] and osmolality were reduced from 136 (SD 2) to 120 mmol/l (SD 3) and from 284 (SD 4) to 252 mosmol/kgH(2)O (SD 5), respectively. The following interpretations were made. First, Edelman's model, which, besides dilution, takes into account Na(+) and K(+), fits plasma [Na(+)] significantly better than dilution alone. Second, a common value of alpha = 1.33 (SD 0.08) and beta = -13.04 mmol/l (SD 7.68) for all pigs explains well the plasma [Na(+)] in the individual animal. Third, measured exchangeable Na(+) and calculated exchangeable Na(+) + K(+) per weight in the pigs are close to Edelman's findings in humans, whereby the methods are cross-validated. In conclusion, plasma [Na(+)] can be explained in the individual animal by external balances, according to Edelman's construct in acute hyponatremia.

Biodistribution of 99mTc-HYNIC-lactadherin in mice--a potential tracer for visualizing apoptosis in vivo.

INTRODUCTION: The aim of this study was to establish a radio synthesis of (99m)Tc-HYNIC-lactadherin for in vivo studies and to perform biodistribution analysis studies in mice, comparing (99m)Tc-HYNIC-lactadherin to (99m)Tc-HYNIC-annexin V. METHODS: The radiochemical purity of (99m)Tc-HYNIC-lactadherin was optimized by varying the amount of SnCl(2) in the synthesis. Furthermore, the need for bovine serum albumin (BSA) as a stabilizing agent was evaluated by following the stability by radiochemical purity measurement with and without the addition of BSA. A total of 24 mice were assigned to groups of 15 and nine mice, respectively. The animals were sacrificed at different time points; 10 min, 60 min, and 180 min. RESULTS: The synthesis of (99m)Tc-HYNIC-lactadherin for in vivo studies has been optimized to give a stable product without addition of BSA and with a radiochemical purity of more than 95%. Approximately 60% of the injected dose of (99m)Tc-HYNIC-lactadherin was found in the liver and 4-5% could be assigned to kidneys. In contrast, (99m)Tc-HYNIC-annexin V distributes with around 13% and 45% of the injected dose in liver and kidneys, respectively. Over the experimental period (10-180 min) only small distributional changes were observed for both probes. CONCLUSION: In conclusion, the biodistribution of (99m)Tc-HYNIC-lactadherin, a potential new tracer for in vivo quantification of apoptosis, was evaluated. The small renal uptake of (99m)Tc-HYNIC-lactadherin makes it possible to image apoptosis in the kidneys, but the high liver clearance may be a disadvantage during myocardial perfusion.

Extravasation of [177Lu]Lu-DOTATOC: case report and discussion.

BACKGROUND: In the case of extravasation of radioactive drugs used in peptide-receptor radionuclide therapy of neuroendocrine tumors, or in radionuclide therapy in general, rapid action is important to reduce or avoid complications. The literature on extravasation of drugs for radionuclide therapy is sparse. Based on the present case, we discuss handling and consequences of extravasation. Further, we demonstrate that dosimetry can aid in judging if the treatment of neuroendocrine tumors is satisfactory even after extravasation. CASE PRESENTATION: A case of extravasation of [177Lu]Lu-DOTATOC with a treatment strategy involving exercise and elevation of the affected arm and application of a compression bandage and heating is reported. Redistribution of the drug is verified and quantified by whole-body imaging and quantitative SPECT/CT and measurements of the dose rate at contact with the injection site. [177Lu]Lu-DOTATOC was redistributed to tumors and organs within 1 day. The patient did not report any discomfort during or after hospitalization, and no side effects related to extravasation were observed. Quantitative SPECT/CT scans at the subsequent treatment cycle of the same patient were analyzed for a comparison between the treatments. Dosimetry showed the treatments were similar with respect to the kidney and tumor absorbed doses. The radiation dose to the epidermal basal layer near the injection site was estimated and found to be consistent with the lack of side effects. CONCLUSIONS: The treatment of extravasation was successful, and the redistribution of the drug can be easily verified through measurement of the dose rate at contact with the skin. From the results of dosimetry, it was assessed that no change of the treatment course was necessary to compensate for a possibly incomplete treatment as a result of the extravasation.

Time and dose-related changes in lung perfusion after definitive radiotherapy for NSCLC.

BACKGROUND AND PURPOSE: To examine radiation-induced changes in regional lung perfusion per dose level in 58 non-small-cell lung cancer (NSCLC) patients treated with intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: NSCLC patients receiving chemo-radiotherapy (RT) of minimum 60 Gy were included prospectively in the study. Lung perfusion single-photon emission computed tomography (SPECT/CT) was performed before and serially after RT. Changes (relative to baseline, %) in regional lung perfusion were correlated with regional dose. Toxicity outcome was radiation pneumonitis (RP) CTC grades 2-5. RESULTS: Perfusion changes were associated with dose. Dose-dependent reduction in regional perfusion was observed at 3, 6 and 12 months of follow-up. Relative perfusion loss per dose bin was 4% at 1 month, 14% at 3 months, 13% at 6 months and 21% at 12 months after RT. In patients with RP, perfusion reduction was larger in high dose lung regions, compared to those without RP. Low dose regions, on the contrary, revealed perfusion gain in the patients with RP. CONCLUSION: Progressive dose dependent perfusion loss is manifested on SPECT up to 12 months following IMRT. These findings suggest that the dynamic change in perfusion may have prognostic value in predicting radiation pneumonitis in NSCLC patients treated with IMRT.

Single photon emission computed tomography (SPECT) and SPECT/low-dose computerized tomography did not increase sensitivity or specificity compared to planar bone scintigraphy for detection of bone metastases in advanced breast cancer.

PURPOSE: To evaluate and compare the diagnostic performance of whole-body planar bone scintigraphy (WBS), single photon emission computed tomography (SPECT), SPECT/low-dose computerized tomography (SPECT/ldCT) and SPECT/contrast enhanced diagnostic CT (SPECT/cdCT) in the staging of patients with advanced breast cancer. METHODS: Seventy-eight patients with recurrence of biopsy-proven breast cancer and suspicion of disseminated disease were investigated with WBS, SPECT, SPECT/ldCT, SPECT/cdCT and MRI performed on the same day in this prospective study. Images were separately analysed in a blinded fashion by radiologists and nuclear medicine physicians regarding the presence of pathological findings. MRI served as reference standard. RESULTS: According to reference standard, 38 of 73 patients had bone metastases. The sensitivity was 87%, 87%, 79%, and 84% and specificity 63%, 71%, 63% and 83% for WBS, SPECT, SPECT/ldCT and SPECT/cdCT. A significantly increased specificity of SPECT/cdCT compared to WBS and SPECT/ldCT was found, and other parameters did not differ significantly between modalities. Additional two patients had bone metastases solely located outside the MRI scan field and seven patients had soft tissue metastases, but no skeletal changes on MRI. CONCLUSION: WBS, SPECT and SPECT/ldCT were less sensitive than MRI and equally specific for the detection of bone metastases in patients with advanced breast cancer. Based on our findings, we suggest that initial staging include WBS, MRI of the spine and CT for soft tissue evaluation. Further studies may clarify the potential benefits of whole-body MRI and 18F-NaF PET/CT or 18F-FDG PET/CT.

Inclusion of functional information from perfusion SPECT improves predictive value of dose-volume parameters in lung toxicity outcome after radiotherapy for non-small cell lung cancer: A prospective study.

BACKGROUND AND PURPOSE: To compare functional and standard dose-volume parameters as predictors of postradiation pulmonary toxicity in lung cancer patients undergoing curative chemo-radiotherapy (RT) studied prospectively. MATERIAL AND METHODS: A total of 58 patients treated with Intensity Modulated RT (60-66Gy) were analysed. Standard dose-volume parameters were extracted from treatment planning computed tomography (CT) scans. Corresponding functional dose-volume parameters were calculated from perfusion single-photon emission computed tomography (SPECT). Primary end-point was radiation pneumonitis (RP) grade 2-5. RESULTS: Functional mean lung dose (MLD) and lung volumes receiving 5, 10, 20 and 30Gy (V5-V30, respectively) revealed high correlation with corresponding standard parameters (r>0.8). Standard MLD, V20 and V30 were significantly higher in patients with RP (p=0.01). All functional parameters were significantly higher in the RP patients (p<0.03). In multivariate analysis functional parameters produced superior risk estimates, while all standard parameters, except V30, were not related to the risk of RP. Area under the curve (AUC) for functional metrics generally exceeded the AUC for corresponding standard parameters, but they were not significantly different from each other. CONCLUSION: SPECT-based functional parameters were better to predict the risk of RP compared to standard CT-based dose-volume parameters. Functional parameters may be useful to guide radiotherapy planning in order to reduce the risk of radiation-induced toxicity.

[Monitoring renal function in patients treated with cytostatics]. / Måling af nyrefunktion under cytostatisk behandling.

INTRODUCTION: Some cytostatics, used in the treatment of cancer, are excreted by the kidneys and may be nephrotoxic. The glomerular filtration rate (GFR) represents a method for reliable assessement of the 51Cr-EDTA plasma clearance before and during treatment with nephrotoxic drugs. The aim of this retrospective study was to evaluate whether this method could be replaced by a more simplified GFR estimate calculated from the creatinine plasma concentration. MATERIALS AND METHODS: We included all patients who had had at least four GFR measurements in 2005 as part of their nephrotoxic cytostatic treatment. The estimated GFR (eGFR) was calculated from sex, age and weight, according to the Cockcroft formula. RESULTS: Forty-eight patients with a mean age of 47 years were included. 51Cr-EDTA plasma clearance and eGFR showed a poor correlation (r(2) = 0,678). On average, GFR decreased from 95 ml/min to 80 ml/min from the first to the fourth measurement, whereas plasma concentration of creatinine and eGFR remained unchanged. In 13 patients (27%), the treatment dose was reduced due to a fall in GFR. Seven of these 13 patients would have continued their treatment unchanged, if the clinical decision had been based on eGFR. CONCLUSION: Neither creatinine plasma concentration nor estimated GFR ad modum Cockcroft can be recommended for measurement of GFR in patients treated with nephrotoxic cytostatics.

Gastric emptying: a comparison of three methods.

OBJECTIVE: A better understanding of the clinical relevance of delayed gastric emptying (e.g. in diabetes) requires a simple, easily accessible and inexpensive method for measuring it. Two "new" methods for measuring gastric emptying of liquids (the paracetamol absorption test and the 13C-acetate breath test) are compared with the gold standard (gastric emptying scintigraphy (GES)). MATERIAL AND METHODS: The three techniques were used simultaneously in 10 healthy subjects. A gastric emptying time-retention curve was drawn for each technique and the results were compared at the 75%, 50% and 25% retention quartiles. RESULTS: Agreement was found between the paracetamol absorption test and GES (p=0.95; Hotelling's T 2 test). Using the Wagner-Nelson one compartment correction produced a retention curve for the 13C-acetate breath test statistically significantly below GES (p<0.01). CONCLUSION: In healthy subjects, the paracetamol absorption test produced results comparable to those of liquid GES, but not to the results of the 13C-acetate breath test.