Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma

Forty-nine patients were treated with either 3 x 75 MBq 89Sr or saline as placebo. Analysis of results 1 to 3 years after therapy revealed the ineffectiveness of 89Sr to relieve pain from metastases. Unexpectedly, a higher survival rate was found after Sr application (46% vs 4% after 2 years). Covariate analysis underlines the effect of 89Sr therapy on life expectation.     

89Sr bremsstrahlung single photon emission computed tomography using a gamma camera for bone metastases

Objective

Strontium-89 chloride (⁸⁹Sr) bremsstrahlung single photon emission computed tomography (SPECT) imaging was evaluated for detecting more detailed whole body ⁸⁹Sr distribution.

Methods

⁸⁹Sr bremsstrahlung whole body planar and merged SPECT images were acquired using two-detector SPECT system. Energy window A (100 keV ± 50 %) for planar imaging and energy window A plus adjacent energy window B (300 keV ± 50 %) for SPECT imaging were set on the continuous spectrum. Thirteen patients with multiple bone metastases were evaluated. Bone metastases can be detected with ^99mTc-HMDP whole body planar and merged SPECT images and compared with ⁸⁹Sr bremsstrahlung whole body planar and merged SPECT images. Based on the location of metastatic lesions seen as hot spots on ^99mTc-HMDP images as a reference, the hot spots on ⁸⁹Sr bremsstrahlung images were divided into the same bone parts as ^99mTc-HMDP images (a total of 35 parts in the whole body), and the number of hot spots were counted. We also evaluated the incidence of extra-osseous uptakes in the intestine on ⁸⁹Sr bremsstrahlung whole body planar images.

Results

A total of 195 bone metastatic lesions were detected in both ^99mTc-HMDP whole body planar and merged SPECT images. Detection of hot spot lesions in ⁸⁹Sr merged SPECT images (127 of 195; 66 %) was more frequent than in ⁸⁹Sr whole body planar images (108 of 195; 56 %), based on metastatic bone lesions in ^99mTc-HMDP whole body planar and merged SPECT images. A large intestinal ⁸⁹Sr accumulation was detected in 5 of the 13 patients (38 %).

Conclusions

⁸⁹Sr bremsstrahlung-merged SPECT imaging could be more useful for detailed detection of whole body ⁸⁹Sr distribution than planar imaging. Intestinal ⁸⁹Sr accumulation due to ⁸⁹Sr physiologic excretion was detected in feces for 4 days after tracer injection.     

Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer

We have used strontium-89 chloride (⁸⁹Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of ⁸⁹Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of ⁸⁹Sr was evaluated at 3 months of treament. Three levels of response were considered: good – when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial – when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response – if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of ⁸⁹Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that ⁸⁹Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose. Received 13 March and in revised form 6 June 1997     

Bone marrow recovery following use of systemic 153Sm-lexidronam and 89Sr-chloride for bone pain palliation after myelosuppressive therapy

Purpose: Using plasma flt3 ((FMS (Friend murine strain))-like tyrosine kinase 3)-ligand cytokine (FL) as a biomarker, the purpose of this study was to determine whether patients receiving palliative radionuclide treatment following chemotherapy experienced enhanced myelosuppression.

Materials and methods: A total of 48 patients with solid tumors who failed multi-agent chemotherapy were investigated; they previously received 1–3 cycles of combination chemotherapy over 4–10 months. Patients were divided into four cohorts including 10 patients with early stage solid tumors prior to chemotherapy induction (naïve group), 10 patients with (non-metastatic) malignancy actively undergoing chemotherapy without radionuclide follow-up (chemotherapy-alone group), 13 patients who underwent standard (1.0 mCi/kg) dose ¹⁵³Sm (¹⁵³samarium)-lexidronam therapy following chemotherapy (¹⁵³Sm group), and 15 patients who underwent standard (4 mCi) dose ⁸⁹Sr (⁸⁹strontium)-chloride therapy following chemotherapy (⁸⁹Sr group). Plasma FL was measured using a quantitative sandwich enzyme immunoassay and CBC (complete blood count), measuring WBC (white blood cell) and PLT (platelet), was performed.

Results: Plasma FL concentration demonstrated a gradual decrease after chemotherapy. In patients who received ¹⁵³Sm within two weeks of completing chemotherapy, there is a distinguishable spike in FL concentration at approximately three weeks after dose administration, which precedes a decrease in WBC and PLT counts. On the other hand, a spike in FL levels in patients who received ⁸⁹Sr therapy is noted at approximately 10 weeks (p < 0.034).

Conclusions: Increases in FL concentration associated with ¹⁵³Sm-lexidronam therapy following combination chemotherapy occurred earlier and returned to control levels more rapidly than did those in patients similarly treated with ⁸⁹Sr. These differences might be associated with the shorter decay half-life and lower particle emission energies of ¹⁵³Sm.     

89Sr radionuclide therapy: Dosimetry and haematological toxicity in two patients with metastasising prostatic carcinoma

We present dosimetry for spinal metastases and red bone marrow in two patients who received ⁸⁹Sr therapy for disseminated prostatic carcinoma. Absorbed dose to metastases was estimated by combining ⁸⁵Sr gamma camera studies with computed tomographic measurements of bone mass, and doses of 20 cGy/MBq and 24 cGy/MBq were found for vertebral metastases that uniformly involved the bodies of L3 and D12 respectively. Absorbed dose to red bone marrow was estimated from total body strontium retention studies using the ICRP model for bone dosimetry, and a ratio of metastatic to marrow dose of around 10 was found in each patient. Although they received comparable treatment activities of around 200 MBq, the patients showed markedly different haematological response, this difference being confirmed when each received a second ⁸⁹Sr treatment 6 months after the first. As a result, clinically significant thrombocytopenia occurred in one patient which prevented further radiostrontium therapy being given.     

Optimal radiation shielding for beta and bremsstrahlung radiation emitted by 89Sr and 90Y: validation by empirical approach and Monte Carlo simulations

Objective

High-energy beta emitters such as Strontium-89 (⁸⁹Sr) and Yttrium-90 (⁹⁰Y) are becoming increasingly popular nuclear therapy sources in Japan for treating cancer. Various characteristics of materials must be considered when designing radiation protection device for high-energy beta emitters. We empirically measured and simulated dose equivalents of beta and bremsstrahlung radiation arising from ⁸⁹Sr and ⁹⁰Y radiation shielded with various materials and determined optimal shielding materials against these sources.

Methods

The dose equivalents of ⁸⁹Sr and ⁹⁰Y determined experimentally using an ionization chamber survey meter were compared with those of Monte Carlo simulations. The relative dose equivalents of beta and bremsstrahlung radiation separately transmitted by changing the thickness of acrylic, aluminum, iron, lead and tungsten shielding materials were simulated.

Results

Dose equivalents were consistent between the empirical measurements and the simulation to within ±5 %. Shielding ability was more effective in the order of tungsten, lead, iron, aluminum and acrylic against both ⁸⁹Sr and ⁹⁰Y. The amount of beta and bremsstrahlung radiation transmitted through tungsten and lead was relatively small. Although such high-density material generates much bremsstrahlung radiation, it absorbs the bremsstrahlung radiations.

Conclusions

Tungsten was the optimal material for efficient shielding against ⁸⁹Sr and ⁹⁰Y radiation and preferable among operators. The present findings provide useful information about how to define an appropriate shielding strategy for high-energy beta emitters.     

Further Studies of Radioactive Strontium and Caesium in Agricultural Crops after Direct Contamination

Summary

Investigations have continued on the extent to which ⁸⁹Sr and ¹³⁷Cs are transferred to the edible parts of cabbage and potato after aerial contamination at various times in the growing season. Significant trends in the concentration of ⁸⁹Sr and ¹³⁷Cs in the hearts of cabbages and ¹³⁷Cs in potato tubers were observed with maximum values after contamination in the middle of the season. A similar trend in the concentrations of ⁸⁹Sr in potato tubers was suggested, but no significant differences could be established. The range of concentrations was of the same order as those found in previous years. The present and earlier results have been used to assess the relationships in the field between the deposition of ⁹⁰Sr and ¹³⁷Cs and their concentration in crops. These relationships show, at least for wheat and potatoes, reasonable agreement with those deduced from surveys of ⁹⁰Sr and ¹³⁷Cs in foodstuffs resulting from the worldwide dissemination of fall-out from nuclear weapons.     

Radioactive Strontium and Caesium in the Edible Parts of Crop Plants after Foliar Contamination

Summary

The degree of contamination of wheat, potato, cabbage and sugar beet has been investigated after the application of ⁸⁹Sr and ¹³⁷Cs in a fine spray at different stages in the growth of the plants. The main experimental treatments were applied over two years to obtain information on seasonal effects. The extent to which ¹³⁷Cs was concentrated in the edible tissues greatly exceeded that of ⁸⁹Sr. Usually the concentration of ⁸⁹Sr or ¹³⁷Cs in each crop varied by less than an order of magnitude irrespective of the state of growth of the crop at the time of contamination and the year in which the experiment was carried out; the ⁸⁹Sr content of wheat grain, however, was considerably lower when the plants were contaminated before the ears emerged. A large part of the radioactivity which was deposited on the leaves was removed rapidly by rain; a further fraction was lost as leaves died. The data obtained have been used to predict the probable degree of contamination of crops growing under normal agricultural conditions.     

New knowledge about the bremsstrahlung image of strontium-89 with the scintillation camera

Objective

Strontium-89 (⁸⁹Sr) chloride has been used to treat metastases in bone. A method to visualize the distribution of ⁸⁹Sr chloride with a scintillation camera was developed in 1996. Studies using bremsstrahlung imaging have shown that ⁸⁹Sr accumulates in bone and that the bremsstrahlung generated from biological tissue surrounding bone does not exceed 30 keV. However, it was not clear how low-energy bremsstrahlung from bone can produce peak energy levels of around 75 keV. We speculate that a different (unidentified) factor is involved.

Methods

The energy spectrum of an ⁸⁹Sr source was acquired with a scintillation camera with or without a low-to-medium-energy general-purpose collimator. The energy window was set at 20–650 keV for 4 windows. A 50-mm thick acrylic block was placed between the scintillation camera and the ⁸⁹Sr source to exclude the effects of bremsstrahlung. The energy spectrum of ⁸⁹Sr covered with lead was acquired using the scintillation camera without a collimator.

Results

With the collimator the energy spectrum curve was similar to that without the 50 mm of acrylic. The energy spectrum curve showed peaks at about 75, 170, and 520 keV. Without the collimator the energy spectrum showed a similar curve but no peak at 75 keV peak. The curve was similar to that obtained with the scintillation camera and the collimator; however, the curve obtained when the ⁸⁹Sr source had been placed in a lead container was similar to that obtained when the source was unshielded, and the collimator was not attached to the scintillation camera.

Conclusion

If bremsstrahlung of ⁸⁹Sr produces an image, a low-energy spectrum region should decrease when acrylic is placed between the ⁸⁹Sr source and the scintillation camera. However, similar curves were obtained both with the acrylic in place and without the acrylic. Therefore, we believe that the radiation detected by the scintillation camera was not bremsstrahlung due to the beta rays of ⁸⁹Sr. Most ⁸⁹Sr preparations are contaminated by ⁸⁵Sr, and most of the gamma ray energy of ⁸⁵Sr is 514 keV. The scintillation camera detected the characteristic X-ray energy of about 75 keV from the materials of the collimator (lead and others) through interaction with the gamma rays of ⁸⁵Sr.

     

89Strontium therapy of bone metastases of carcinoma of the prostatic gland

Following a firm diagnostic and therapeutic schedule for patients with prostatic carcinoma, ⁸⁹Strontium therapy was introduced for multiple metastases. Positive skeletal scintigraphy with ^99mTc-EHDP induced check for affinity to Sr using ⁸⁵Sr scintigraphy. Of 80 patients, multiple metastases were found in 26. Therapy with 1 mCi of ⁸⁹Sr-chloride was started in 20 cases. In 8 patients, relief from severe pain appeared shortly afterward, and a further 8 it was possible to prevent the development of pain. Moderate success in 3 cases and a failure to provide relief in 1 were observed.     

Sr-89 therapy: Strontium kinetics in disseminated carcinoma of the prostate

Strontium kinetics were investigated in a group of 14 patients receiving ⁸⁹Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using ⁸⁵Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following ⁸⁹Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t<6 days, and was an important secondary factor at later times. Over the interval 30 days t<90 days, R(t) was closely fitted by the power law function R(t)=R ₃₀ (t/30)^-b, with R ₃₀ and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t^-0.2 power law function. The changes in strontium kinetics found in metastatic bone disease are favourable to the objectives of ⁸⁹Sr therapy.     

Validation of rapid methods for the determination of radiostrontium in milk

A rapid method of ⁸⁹Sr and ⁹⁰Sr comprising ion chromatography for preconcentration and Sr extraction chromatography for separation of Sr from Ca, Ba and Y was validated with spiked milk samples. An ⁸⁹Sr/⁹⁰Sr activity ratio of up to 12 showed the relative bias was within ±20%. The separation time of Sr was 7 h and the chemical recovery of Sr ranged from 80% to 95%. The detection limit for 500 mL milk and 90 min counting time was 0.1 Bq L⁻¹.     

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after⁸⁹Sr administration. Patients received 2 MBq/kg (118–148 MBq) of⁸⁹Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that⁸⁹Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.     

Measurements of the strontium plasma clearance rate in patients receiving 89Sr radionuclide therapy

The total strontium plasma clearance rate due to excretion through the kidneys and gut has an imporant influence on the absorbed does delivered to skeletal metastases and red bone marrow in patients receiving ⁸⁹Sr radionuclide therapy for disseminated prostatic carcinoma. Although a measurement of the renal strontium plasma clearance rate may readily be obtained through a 24-h urine collection, little information is available on the correlation between renal and total clearances. We describe a method of determining total strontium plasma clearance rate from whole body counter measurements of total body strontium retention and measurements of plasma strontium concentration following administration of a ⁸⁵Sr tracer dose at the time of ⁸⁹Sr therapy. Amongst the 26 patients whom we studied, the total clearance rate varied from 1.2–15.0 l/day, renal clearance rate from 0.1–11.5 l/day, and the mean gut clearance rate was 2.0 l/day. A close correlation was found between total and renal clearance, with the renal component accounting for 96% of the variance in total strontium plasma clearance. A weak collection may exist between gut and renal clearance.     

Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients

Most studies of prostate cancer have shown that strontium-89 chloride (89Sr) is effective in the palliation of metastatic bone pain, refractory to conventional analgesia. The aim of this study was to evaluate the usefulness of 89Sr for bone pain palliation in breast cancer patients. Forty women were treated with 148 MBq of 89Sr. Six patients were retreated, receiving two or more doses. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. The response was good in 60% of the patients and partial in 32%; there was no response in the remaining 8% (pre-treatment Karnofsky < or = 60). The duration of the response was 120+/-143 days. In the patients retreated, the response was good in 83% and partial in 17%, without significant differences compared with the first dose, but the pre-treatment Karnofsky and the duration of the efficacy were lower (P < 0.05). A transient and slight decrease of leukocyte and platelet counts after the first month of treatment with 59Sr was observed. In conclusion, breast cancer patients with metastatic bone pain can benefit from therapy with 89Sr. If necessary, the treatment may be repeated safely and with the same efficacy as is achieved after the first dose. A low functional performance status could be a cause of the lower effectiveness of 89Sr.     

Gamma camera imaging of osseous metastatic lesions by strontium-89 bremsstrahlung

The aim of this study was to optimise the parameters affecting the Bremsstrahlung scintigraphy of patients injected with strontium-89 chloride. The parameters considered were : (1) instrumental detection efficiency, and (2) tissue attenuation factor for ⁸⁹Sr calibrated sources, which permit quantitative evaluation of the activity in a given bone lesion. Some typical examples of in vivo ⁸⁹Sr imaging are presented to illustrate the clinical utility of the imaging procedure developed by us, which is implemented in our department for all patients treated with ⁸⁹Sr chloride. Received 7 April and in revised form 14 July 1997     

Handling interferences in 89Sr and 90Sr measurements of reactor coolant water: A method based on strontium separation chemistry

Measurements for determining the activity of ⁸⁹Sr and ⁹⁰Sr in reactor coolant water are associated with limitations due to interferences from radionuclides with similar chemical properties and β⁻-energies. From a measurement bias point-of-view these interferences would result mainly in an overestimated activity concentration of ⁹⁰Sr.In order to address the interference problem, a common and well-known method was used in order to show the need for sufficient decontamination. An improvement was achieved by taking the sample through two initial strontium separations in order to increase the decontamination factor. This method determines the activity concentration of ⁸⁹Sr and ⁹⁰Sr, via its daughter nuclide ⁹⁰Y, by Cherenkov counting. This work is primarily based on theoretical calculations of strontium-, yttrium- and other potential interfering radionuclide ratios after instant fission. The work done to confirm the theoretical calculations were carried through on spiked strontium standard solutions and fresh reactor coolant water. The reactor coolant water was known to contain interferences at a composition resembling that of instant fission. The detection limit for double separation was calculated to 0.17 Bq/kg for ⁹⁰Sr and 0.38 Bq/kg for ⁸⁹Sr. When using methods that solely rely on strontium resins, this paper shows that the decontamination factor (DF) is significantly higher when using double separation than that of a single separation. The paper also shows that the DF of an initial double strontium separation is as effective when it comes to removing high ratio interferences as separations done with both Sr- and Ln-resin (EiChrom Technologies, Inc., 2003, Tovedal et al., 2009b). However, ‘old’ samples, where e.g. ¹⁴⁰Ba and ⁸⁹Sr has decayed, does not benefit from double separation. Furthermore, samples with low ratios of interfering radionuclides does not benefit from using this method either, seeing as this is a more time consuming method due to the double separations.     

Effects of Irradiation on the Mediterranean Meal Moth,Ephestia Kuehniella Zeller,Cultured on 89Sr-spiked Food

Summary

Ephestia kuehniella Zeller was cultured on corn-meal spiked with ⁸⁹Sr at concentrations of 0, 0·1, 0·3, 1·0, 3·0 and 5·0 µc/g of food.

As the environmental radiation was increased, the adults which were subjected throughout their life-cycle produced progressively fewer progeny.

5·0 µc ⁸⁹Sr/g food approaches the critical level which will inhibit population development.

Life-span of the adults was not influenced by the experimental conditions.

Delayed development occurred at all isotopic concentrations employed.

The radiostrontium-content of females at the end of their life-cycle was half that of males. Twenty-four hours after eclosion, the radioactivity of the female moth was equal to, or greater than, that of corresponding males. Reproductive metabolism is offered in explanation.

At the two highest culture levels (3 and 5 µc ⁸⁹Sr/g), the increased number of males (homogametic sex) over females (heterogametic sex) is consistent with the radiation genetic effect of induced recessive lethals. No selective radiation effect upon the sexual capacity of gametes of the F₁ was indicated, since the subsequent F₂ sex ratio was 1 : 1.     

89SrCl2在治疗乳腺癌骨转移中的临床疗效

目的 评价⁸⁹SrCl₂治疗乳腺癌骨转移的临床疗效,及其血液学毒副作用。方法 51例患者接受⁸⁹SrCl₂治疗,静脉注射剂量为2.22 MBq/kg体重,观察治疗前后止痛效果,病灶变化和外周血细胞变化。结果 患者疼痛完全缓解率为37.7%(17/45),总缓解率为84.4%。病灶治疗有效率为62.7%(32/51)。治疗后1个月白细胞和血小板减少者分别为76.5%和62.7%。3个月后大多数患者经治疗血象恢复到正常。结论 ⁸⁹SrCl₂可安全、有效地治疗乳腺癌骨转移患者的疼痛,并对其生活质量有所改善。     

p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging

Purpose

Immuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAbs) for imaging and therapy. The positron emitter zirconium-89 (⁸⁹Zr) has attractive characteristics for immuno-PET with intact mAbs. Previously, we have described a multi-step procedure for stable coupling of ⁸⁹Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol-N-succinyldesferal (TFP-N-sucDf). To enable widespread use of ⁸⁹Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in ⁸⁹Zr-immuno-PET with the reference BFC TFP-N-sucDf.

Methods

Three mAbs were premodified with Df-Bz-NCS and labeled with ⁸⁹Zr at different pHs to assess the reaction kinetics and robustness of the radiolabeling. Stability of both ⁸⁹Zr-Df-Bz-NCS- and ⁸⁹Zr-N-sucDf-conjugates was evaluated in different buffers and human serum. Comparative biodistribution and PET studies in tumor-bearing mice were undertaken.

Results

The selected conjugation conditions resulted in a chelate:mAb substitution ratio of about 1.5:1. Under optimal radiolabeling conditions (pH between 6.8–7.2), the radiochemical yield was >85% after 60 min incubation at room temperature, resulting in radioimmunoconjugates with preserved integrity and immunoreactivity. The new radioimmunoconjugate was very stable in serum for up to 7 days at 37°C, with <5% ⁸⁹Zr release, and was equally stable compared to the reference conjugate when stored in the appropriate buffer at 4°C. In biodistribution and imaging experiments, the novel and the reference radioimmunoconjugates showed high and similar accumulation in tumors in nude mice.

Conclusions

The novel Df-Bz-NCS BFC allows efficient and easy preparation of optimally performing ⁸⁹Zr-labeled mAbs, facilitating further exploration of ⁸⁹Zr-immuno-PET as an imaging tool.