Knut Liepe

A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases.

AimThe surface bone-seeking radiopharmaceuticals 188Re-HEDP, 186Re-HEDP and 153Sm-EDTMP, and the volume seeker 89Sr were investigated to determine the efficacy and toxicity in pain palliation of bone metastases. MethodThe effect of treatment with 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr on pain symptoms, quality of life, and bone marrow function were studied. In total, 79 patients (18 with breast cancer and 61 with prostate cancer) were treated (31 patients with 188Re-HEDP, 15 patients each with 186Re-HEDP and 153Sm-EDTMP, and 18 patients with 89Sr). All patients were interviewed using standardized sets of questions before and after therapy weekly for 12 weeks. Blood counts were taken weekly for 6 weeks and after 12 weeks. ResultsIn total, 73% of patients reported pain relief (77% after 188Re-HEDP, 67% after 186Re-HEDP 73% after 153Sm-EDTMP, and 72% after 89Sr). Fifteen percent of patients could discontinue their analgesics and were pain-free. Pain showed a decrease from 3.6±1.7 to a maximum of 2.2±1.8 at visual analogue scale in 10 steps (P<0.01). Patients described an improvement on the Karnofsky performance scale from 70±10% to 78±14% 12 weeks after treatment (P=0.15). There were eight patients with a thrombocytopenia grade I, two patients with grade II and one with grade III. The maximum nadir of platelet and leukocyte counts were observed between the 2nd to 5th week after treatment and was reversible within 12 weeks. There were no significant differences in pain palliation, Karnofsky performance status (KPS) and bone marrow toxicity between the different radionuclides (P=0.087–0.449). ConclusionAll radiopharmaceuticals were effective in pain palliation, without induction of severe side effects or significant differences in therapeutic efficacy or toxicity.

Systemic radionuclide therapy in pain palliation

Several radiopharmaceuticals were investigated to determine their efficacy and toxicity in the palliation of painful bone metastases. Data on the influence of rhenium-188 hydroxyethylidene diphosphonate ( 188 Re-HEDP), rhenium-186 hydroxyethylidene diphosphonate ( 186 Re-HEDP), and strontium-89 ( 89 Sr) on pain symptoms, quality of life, and bone-marrow function were obtained in 64 patients with breast and prostate cancer. Thirty-one patients were treated with 188 Re-HEDP (3194 ± 387 MBq), 15 patients with 186 Re-HEDP (1358 ± 158 MBq), and 18 patients with 89 Sr (152 ± 19 MBq). The 188 Re-HEDP group included six breast cancer patients and 25 prostate cancer patients; the 186 Re-HEDP group included three breast cancer patients and 12 prostate cancer patients; and the 89 Sr group included three breast cancer patients and 15 prostate cancer patients. All subjects participated in an interview using a standardized sets of questions before and after the 12-week term of therapy. Blood counts were taken weekly for six weeks and after 12 weeks. Results showed that 77 percent of patients reported pain relief after treatment with 188 Re-HEDP, 67 percent after treatment with 186 Re-HEDP, and 72 percent after treatment with 89 Sr. Sixteen percent of patients treated with 188 Re-HEDP, 13 percent treated with 186 Re-HEDP, and 17 percent treated with 89 Sr were able to discontinue their analgesics and were pain-free. Patients described an improvement on Karnofsky performance status (KPS) from 73 ± 7 percent to 85 ± 8 percent 12 weeks after 188 Re-HEDP (p < 0.05), from 72 ± 13 percent to 79 ± 12 percent after 186 Re-HEDP (p = 0.251), and from 62 ± 14 percent to 69 ± 16 percent after 89 Sr (p = 0.415). Only three patients undergoing 188 Re-HEDP therapy, one undergoing 186 Re-HEDP therapy, and three undergoing 89 Sr therapy had thrombocytopenia (platelet count below 100 × 10(3)/µl) following treatment. The maximum nadir of platelet and leukocyte counts was observed between the second and fifth week after treatment for all radionuclides and was reversible within 12 weeks. The nadir was earlier for 188 Re-HEDP with a shorter physical half-life compared with 89 Sr. There were no significant differences in bone marrow toxicity (p = 0.123-0.421). Results of this study indicate that all evaluated radiopharmaceuticals were effective in pain palliation without induction of severe side effects. The increase in KPS after 188 Re-HEDP was the only statistically significant finding (p = 0.001).

Radiosynoviorthesis (RSO): influencing factors and therapy monitoring

ObjectiveTo evaluate the effectiveness of radiosynoviorthesis (RSO) in relation to joint type and underlying disease by both self-assessment of patients and scintigraphic assessment to determine conditions under which RSO might be preferable to the sole intra-articular corticoid injection.MethodsRadiosynoviorthesis was performed on 136 patients for 424 joints [242 small, 130 medium-sized, and 52 large joints; 313 with rheumatoid arthritis (RA) and 111 with osteoarthritis (OA)]. The success of RSO was evaluated after 12 months by patients’ estimation, and in 35 patients for 157 joints additionally by two-phase bone scintigraphy. The relative change in the scintigraphic uptake was compared with the patients’ estimation.ResultsThe subjectively estimated success rates for the small, medium-sized, and large joints were 89% (215/242), 86% (112/130), and 79% (41/52), and for RA and OA 89% (280/313) and 79% (88/111), respectively. The scintigraphically determined response rates for small and medium-sized joints were 81% (86/106) and 69% (35/51), respectively. There was a mismatch between patients’ assessment and scintigraphic assessments in 18% (28/157) with 6 false-negative and 22 false-positive estimations using scintigraphy as the standard of reference.ConclusionsThe success of RSO is higher in patients with RA than in patients with OA. For the finger, ankle, and wrist joints in RA, RSO is so promising that we would like to advocate its preference over the sole intraarticular corticoid injection. Perfusion bone scintigraphy can be used for therapy monitoring and earlier switching to RSO by showing that other therapies have failed.

Autoradiographic studies of rhenium-188-hydroxyethylidine diphosphonate in normal skeleton and osteoblastic bone metastases in a rat model of metastatic prostate cancer.

AimThe quantitative distribution of bone-seeking radiopharmaceuticals in trabecular bone, cortical bone and in skeletal metastases is required for calculation of radiation-absorbed dose in radionuclide therapy. An animal model of intraosseous tumor cell administration was developed to simulate osteoblastic metastases for autoradiographic study of radionuclide localization. MethodsIn 45 Copenhagen rats R3327-MATLyLu syngeneic prostate cancer cells were given intraosseously in both the femori. Rhenium-188-hydroxyethylidine diphosphonate (HEDP) was administered intravenously 17±1 days after cells instillation and these animals were euthanized at 4, 24 and 48 h after injection of the radiopharmaceutical. The uptake of radiopharmaceutical was estimated in normal skeleton and the bone metastases by means of region of interest analysis using autoradiography. The tumor to nontumor ratio and the fractional uptake in cortical bone and trabecular bone were quantified. ResultsThe uptake of rhenium-188-HEDP in cortical bone was 33.5% and in trabecular bones was 66.5% after 4 h, 34.6 and 65.4% after 24 h, and 35.9 and 64.1% after 48 h, respectively. Assuming a theoretic cortical-trabecular distribution of 50–50%, (MIRDOSE) calculation, radiation-absorbed dose to bone marrow was underestimated by 26%. In bone metastases, an inhomogeneous distribution with a minimal and maximal tumor to nontumor ratio of 3 : 1 and 14 : 1 after 4 h, 5 : 1 and 14 : 1 after 24 h, and 5 : 1 and 16 : 1 after 48 h was observed. ConclusionThe MIRDOSE model underestimates the radiation-absorbed dose to the bone marrow because of demonstrable differences in the uptake of rhenium-188-HEDP in cortical and trabecular bone and inhomogeneous uptake in skeletal metastases.

Dose-dependent histological alterations in the rat lung following intravenous application of Re-188-labeled microspheres.

Abstract Purpose: The objective of this study was to determine the dose-effect correlation of pneumopathy after application of Rhenium-188 microspheres (Re-188 MS) in an animal model using histological changes as an end-point. Methods and materials: Wistar rats received an intravenous injection of Re-188 MS yielding doses that ranged from ˜ 2 to ˜ 55 Gy. Lungs were removed after ˜ 25 weeks and prepared for histology. Sections were evaluated using a semi-quantitative 5-tiered score. Dose groups of 10 Gy intervals were statistically analyzed using the Chi-square test with respect to grade and extent of connective tissue accumulation, thickness of vessel walls and accumulation of alveolar macrophages (AM). Results: There was a statistically significant increase in connective tissue content and extent in all dose groups compared to control lungs and at least between each other dose group. The steepest increase in connective tissue was at doses higher than 40 Gy. Starting from that dose, a statistically significant increase of AM accumulation and vessel wall thickness occurred. Conclusions: There was a clear dose-effect correlation between radiation dose and histological changes. These findings allow an estimation of potential normal tissue damage especially during tumor treatments of liver lesions with radioactive particles in patients with significant liver-to-lung shunts.